Managing Chronic Hepatitis C in the Primary Care Setting: Best ...€¦ · Managing Chronic...
85
Ricardo A. Franco, MD Assistant Professor of Medicine Division of Infectious Disease University of Alabama at Birmingham Birmingham, Alabama Managing Chronic Hepatitis C in the Primary Care Setting: Best Practices From Screening to Treatment This CME activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education. This activity is supported by an educational grant from Gilead Sciences, Inc.
Managing Chronic Hepatitis C in the Primary Care Setting: Best ...€¦ · Managing Chronic Hepatitis C in the Primary Care Setting: Best Practices From Screening to Treatment This
Ricardo A Franco MDAssistant Professor of MedicineDivision of Infectious DiseaseUniversity of Alabama at Birmingham Birmingham Alabama
Managing Chronic Hepatitis C in the Primary Care Setting Best Practices From Screening to Treatment
This CME activity is jointly provided by Medical Learning Institute Inc and PVI PeerView Institute for Medical Education
This activity is supported by an educational grant from Gilead Sciences Inc
Managing Chronic Hepatitis C in the Primary Care Setting Best Practices From Screening to Treatment
Ricardo A Franco MD has a financial interestrelationship or affiliation in the form ofConsultant For GileadGrantResearch Support from Gilead Merck amp Co Inc Janssen Pharmaceuticals Inc and OraSure Technologies Inc
This CME activity is jointly provided by Medical Learning Institute Inc and PVI PeerView Institute for Medical Education
This activity is supported by an educational grant from Gilead Sciences Inc
Identifying and Overcoming Barriers to HCV Screening and Diagnosis in Primary Care
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
HCV hepatitis C virus1 Messina JP et al Hepatology 20156177-87
Prevalence of HCV Infection in the United States1-3
bull 27 to 50 million living with chronic HCV in the United States
bull 45-60 unaware of infectionbull Not included or underestimated in
NHANES estimate ndash Homeless
(142761-337610)ndash Incarcerated
(372754-664826)ndash Veterans
(1237461-2452006)ndash Active military
(6805)ndash Healthcare workers
(64809-259234)
NHANES National Health and Nutrition Examination Survey1 Denniston M et al Ann Intern Med 2014160293-300 2 Chak E et al Liver Int 2011311090-1101 3 Zalesak M et al PLoS One 20138e63959
Chart1
Conservative Estimate
Upper limit estimate
Millions of Cases
Estimated HCV Cases
52
71
19
38
32
Sheet1
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
1 Zibbell JE et al MMWR Morb Mortal Wkly Rep 201564453-458
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Black
HisplanicLatino
White
2005
38
19
38
2009
29
21
44
2012
28
21
44
2015
19
21
54
To resize chart data range drag lower right corner of range
2005
2005
2005
2009
2009
2009
2012
2012
2012
2015
2015
2015
Conservative Estimate
Upper limit estimate
Total
52
71
Not included in NHANES
19
38
NHANES
32
To resize chart data range drag lower right corner of range
Total
Total
Not included in NHANES
Not included in NHANES
NHANES
NHANES
Managing Chronic Hepatitis C in the Primary Care Setting Best Practices From Screening to Treatment
Ricardo A Franco MD has a financial interestrelationship or affiliation in the form ofConsultant For GileadGrantResearch Support from Gilead Merck amp Co Inc Janssen Pharmaceuticals Inc and OraSure Technologies Inc
This CME activity is jointly provided by Medical Learning Institute Inc and PVI PeerView Institute for Medical Education
This activity is supported by an educational grant from Gilead Sciences Inc
Identifying and Overcoming Barriers to HCV Screening and Diagnosis in Primary Care
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
HCV hepatitis C virus1 Messina JP et al Hepatology 20156177-87
Prevalence of HCV Infection in the United States1-3
bull 27 to 50 million living with chronic HCV in the United States
bull 45-60 unaware of infectionbull Not included or underestimated in
NHANES estimate ndash Homeless
(142761-337610)ndash Incarcerated
(372754-664826)ndash Veterans
(1237461-2452006)ndash Active military
(6805)ndash Healthcare workers
(64809-259234)
NHANES National Health and Nutrition Examination Survey1 Denniston M et al Ann Intern Med 2014160293-300 2 Chak E et al Liver Int 2011311090-1101 3 Zalesak M et al PLoS One 20138e63959
Chart1
Conservative Estimate
Upper limit estimate
Millions of Cases
Estimated HCV Cases
52
71
19
38
32
Sheet1
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
1 Zibbell JE et al MMWR Morb Mortal Wkly Rep 201564453-458
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Black
HisplanicLatino
White
2005
38
19
38
2009
29
21
44
2012
28
21
44
2015
19
21
54
To resize chart data range drag lower right corner of range
2005
2005
2005
2009
2009
2009
2012
2012
2012
2015
2015
2015
Conservative Estimate
Upper limit estimate
Total
52
71
Not included in NHANES
19
38
NHANES
32
To resize chart data range drag lower right corner of range
Total
Total
Not included in NHANES
Not included in NHANES
NHANES
NHANES
Identifying and Overcoming Barriers to HCV Screening and Diagnosis in Primary Care
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
HCV hepatitis C virus1 Messina JP et al Hepatology 20156177-87
Prevalence of HCV Infection in the United States1-3
bull 27 to 50 million living with chronic HCV in the United States
bull 45-60 unaware of infectionbull Not included or underestimated in
NHANES estimate ndash Homeless
(142761-337610)ndash Incarcerated
(372754-664826)ndash Veterans
(1237461-2452006)ndash Active military
(6805)ndash Healthcare workers
(64809-259234)
NHANES National Health and Nutrition Examination Survey1 Denniston M et al Ann Intern Med 2014160293-300 2 Chak E et al Liver Int 2011311090-1101 3 Zalesak M et al PLoS One 20138e63959
Chart1
Conservative Estimate
Upper limit estimate
Millions of Cases
Estimated HCV Cases
52
71
19
38
32
Sheet1
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
1 Zibbell JE et al MMWR Morb Mortal Wkly Rep 201564453-458
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Black
HisplanicLatino
White
2005
38
19
38
2009
29
21
44
2012
28
21
44
2015
19
21
54
To resize chart data range drag lower right corner of range
2005
2005
2005
2009
2009
2009
2012
2012
2012
2015
2015
2015
Conservative Estimate
Upper limit estimate
Total
52
71
Not included in NHANES
19
38
NHANES
32
To resize chart data range drag lower right corner of range
Total
Total
Not included in NHANES
Not included in NHANES
NHANES
NHANES
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
HCV hepatitis C virus1 Messina JP et al Hepatology 20156177-87
Prevalence of HCV Infection in the United States1-3
bull 27 to 50 million living with chronic HCV in the United States
bull 45-60 unaware of infectionbull Not included or underestimated in
NHANES estimate ndash Homeless
(142761-337610)ndash Incarcerated
(372754-664826)ndash Veterans
(1237461-2452006)ndash Active military
(6805)ndash Healthcare workers
(64809-259234)
NHANES National Health and Nutrition Examination Survey1 Denniston M et al Ann Intern Med 2014160293-300 2 Chak E et al Liver Int 2011311090-1101 3 Zalesak M et al PLoS One 20138e63959
Chart1
Conservative Estimate
Upper limit estimate
Millions of Cases
Estimated HCV Cases
52
71
19
38
32
Sheet1
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
1 Zibbell JE et al MMWR Morb Mortal Wkly Rep 201564453-458
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Black
HisplanicLatino
White
2005
38
19
38
2009
29
21
44
2012
28
21
44
2015
19
21
54
To resize chart data range drag lower right corner of range
2005
2005
2005
2009
2009
2009
2012
2012
2012
2015
2015
2015
Conservative Estimate
Upper limit estimate
Total
52
71
Not included in NHANES
19
38
NHANES
32
To resize chart data range drag lower right corner of range
Total
Total
Not included in NHANES
Not included in NHANES
NHANES
NHANES
Prevalence of HCV Infection in the United States1-3
bull 27 to 50 million living with chronic HCV in the United States
bull 45-60 unaware of infectionbull Not included or underestimated in
NHANES estimate ndash Homeless
(142761-337610)ndash Incarcerated
(372754-664826)ndash Veterans
(1237461-2452006)ndash Active military
(6805)ndash Healthcare workers
(64809-259234)
NHANES National Health and Nutrition Examination Survey1 Denniston M et al Ann Intern Med 2014160293-300 2 Chak E et al Liver Int 2011311090-1101 3 Zalesak M et al PLoS One 20138e63959
Chart1
Conservative Estimate
Upper limit estimate
Millions of Cases
Estimated HCV Cases
52
71
19
38
32
Sheet1
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
1 Zibbell JE et al MMWR Morb Mortal Wkly Rep 201564453-458
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Chronic HCV infection can lead to the development of fibrous scar tissue within the liver
Cirrhosis12
Over time fibrosis can progress causing severe scarring of the liver restricted blood flow impaired liver function and eventually liver failure
HCC3
Cancer of the liver can develop after years of chronic HCV infection
HCC hepatocellular carcinoma1 Highleyman L Hepatitis C Support Project httpwwwhcvadvocateorghepatitisfactsheets_pdfFibrosispdf Accessed April 18 2017 2 Bataller R et al J Clin Invest 2005115209-2183 El-Serag HB N Engl J Med 20113651118-11274 httpwwwcdcgovhepatitisHCVHCVfaqhtm Accessed April 18 2017
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
HCV Underdiagnosis and Undertreatment1
Despite its high prevalence and increasing disease burden chronic HCV has not been diagnosed in most Americans with this
disease and few cases have been treated
0
10
20
30
40
50
60
Diagnosed Referred toCare
Treated SuccessfullyTreated
Overall 32 Million of US Population Have Chronic HCV
7-11(220000-360000)
5-6(170000-200000)
50(16M)
32-38(10-12M)
1 Holmberg SD et al N Engl J Med 20133681859-1861
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Chart1
2
05
032
007
005
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Diagnosed
Referred to Care
Treated
Successfully Treated
Sheet1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
2
Diagnosed
05
Referred to Care
032
Treated
007
Successfully Treated
005
To resize chart data range drag lower right corner of range
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
0 1 2 3 4 5 6 1 2 3 4Months
Time After ExposureYears
Symptoms plusmnAnti-HCVALT
Normal
Tite
r
HCV RNA
1 Hoofnagle JH Hepatology 19972615S-20S
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Potential Barriers to HCV Identification12
Patients reluctant to discuss HCV risk factorsPatient Barriers
Stigmatization of HCV infection in healthcare system and community
Systemic Barriers
Healthcare professionals may be unaware of or reluctant to ask about risk factors
Clinician Barriers
1 Institute of Medicine Hepatitis and Liver Cancer A National Strategy for Prevention and Control of Hepatitis B and C Washington DC The National Academies Press 20102 US Department of Health and Human Services Combating the Silent Epidemic of Viral Hepatitis Action Plan for the Prevention Care and Treatment of Viral Hepatitis Washington DC USDHHS 2011
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
CDC Recommendationsbull Everyone born from 1945 through
1965 (one time)bull Persons who ever injected illegal drugsbull Persons who received clotting factor
concentrates produced before 1987bull Recipients of chronic (long-term)
hemodialysisbull Persons with persistently abnormal
ALT levels bull Recipients of transfusions or organ
transplants prior to 1992bull Persons with recognized occupational
exposuresbull Children born to HCV-positive womenbull HIV-positive persons
USPSTF Grade B Recommendationsa
bull Everyone born from 1945 through 1965 (one time)
bull Past or present injection drug use bull Sex with an injection drug user other
high-risk sexbull Blood transfusion prior to 1992bull Persons with hemophiliabull Long-term hemodialysisbull Born to an HCV-infected motherbull Incarcerationbull Intranasal drug usebull Receiving an unregulated tattoobull Occupational percutaneous exposurebull Surgery before implementation of
universal precautions
a Only pertains to persons with normal liver enzymes if elevated liver enzymes need hepatitis B virus and HCV testingUSPSTF US Preventive Services Task Force1 Smith BD et al Ann Intern Med 2012157817-8222 Moyer VA et al Ann Intern Med 2013159349-357
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
bull Up to 75 of people with HCV in the United States are undiagnosedbull An estimated 35 of Baby Boomers with undiagnosed HCV currently have advanced
fibrosis (F3-F4 bridging fibrosis to cirrhosis)3
1990+1980s1970s1960s1950s1940s1930s1920slt1920
Estimated Prevalence by Age Group2
Num
ber W
ith C
hron
ic H
CV
Infe
ctio
n m
illio
ns
Birth Year Group
0
16
14
12
10
08
06
04
02
1 CDC MMWR Morb Mortal Wkly Rep 2012611-18 2 Adapted from Pyenson B et al Consequences of Hepatitis C Virus (HCV) Costs of a Baby Boomer Epidemic of Liver Disease New York NY Milliman Inc 2009 httpwwwmillimancomexpertisehealthcarepublicationsrrconsequences-hepatitis-c-virus-RR05-15-09php Accessed April 18 2017 3 McGarry LJ et al Hepatology 2012551344-1355
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
a Cured with PEG-IFN and RBV plus direct-acting antiviral treatment b Deaths due to decompensated cirrhosis or HCC within the 1945-1965 birth cohort 470000 deaths under birth-cohort screening vs 592000 deaths under risk-based screeningPEG-IFN pegylated interferon RVB ribavirin1 Rein DB et al Ann Intern Med 2012156263-2702 McGarry LJ et al Hepatology 2012551344-1355
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Past or present injection drug users
Those who have had sex with an injection drug user or who engaged in other high-risk sexual behaviors
Recipients of blood transfusion or organ transplant prior to 1992
Those with hemophilia
Recipients of long-term hemodialysis
Those with HIV infection
Those born to an HCV-infected mother
Persons who have been or who are incarcerated
Other At-Risk Groups Who Should Be Screened1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Those with history of intranasal drug use
Long-term daily alcohol users
Those who have received an unregulated tattoo
Those with history of occupational percutaneous exposure
Those who underwent surgery before implementation of universalprecautions
Those with persistently elevated ALT levels
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
1 Smith BD et al MMWR Recomm Rep 2012611-32 2 Moyer VA et al Ann Intern Med 2013159349-357 3 World Health Organization April 2014 wwwwhoint
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Talking to Patients About Hepatitis C Testing1
Aim Sample Conversation
Provide rationale for testing ldquoItrsquos commonrdquo
Provide reassurance about testing ldquoItrsquos curablerdquo
Obtain consent ldquoIf it is alright with you I would like to test you for hepatitis C todayrdquo
1 httpswwwcdcgovhepatitisresourcesprofessionalspdfscounselingandtestingpdf Accessed June 7 2017
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Screening Tests for HCV1-4
ELISA Screening Tests
bull Serologic assays to detect circulating HCV antibodies
bull Sensitivity (97-100)bull Positive predictive value
ndash 95 with risk factors + elevated ALTndash 50 without risk factors + normal ALT
bull False-positive resultsndash More likely in patients with low risk of
HCV infectionbull False-negative results
ndash More likely in severely immunocompromised patients
HCV RNA Assays
bull Use sensitive quantitative assaybull When to test
ndash If anti-HCV Ab test result is positive
ndash If antiviral treatment is being considered
ndash If unexplained liver disease and anti-HCV Ab test result is negative and person is immunocompromised
ndash If acute HCV infection is suspected
Ab antibody ELISA enzyme-linked immunosorbent assay1 AASLD and IDSA Recommendations for testing managing and treating hepatitis C httpwwwhcvguidelinesorgfull-report-view Accessed April 18 20172 Smith BD et al MMWR Recomm Rep 2012611-32 3 Moyer VA et al Ann Intern Med 2013159349-357 4 World Health Organization April 2014 wwwwhoint
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Recommended Testing Sequence for Identifying Current HCV Infection1
1 httpswwwcdcgovhepatitisHCVPDFshcv_flowpdf Accessed May 3 2017
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
bull Educate regarding HCV transmissionndash Screen sexual partners but CDC does not
recommend barrier methods for monogamous heterosexual partners
ndash Higher risk of sexual transmission among MSM particularly those with HIV infection
ndash Children born to HCV-positive mothers should be screened (lt3 risk)
bull Screen for immunity to hepatitis A Ab total and hepatitis B (HBsAb) and vaccinate if non-immune
MSM men who have sex with men
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
bull Assess alcohol use in all patients with HCV (CDC guidelines)ndash There is no ldquosaferdquo amount of alcohol consumption for
patients with HCVndash Refer patients with risky use for alcohol treatment
Men gt2 drinksday (gt14week) or more than 4 in one day Women gt1 drinkday (gt7week) or more than 3 in one day
bull Advise on a liver-healthy diet which equates to a normal body mass index
HBsAb hepatitis B surface antibody test
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
All persons with current active HCV infection should be linked to a practitioner who is prepared
to provide comprehensive management1
CURE IS POSSIBLE
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
A Closer Look at Current Recommendations and Options for the Treatment of HCV
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Goal of HCV Therapy1a
The goal of treatment of HCV-infected persons is to reduce all-cause mortality and liver-related health adverse consequences including end-stage liver
disease and hepatocellular carcinoma by the achievement of virologic cure as evidenced by a
sustained virologic response (SVR)
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
When and in Whom to Initiate HCV Therapy1a
Treatment is recommended for all patients with chronic HCV infection except those with short life expectancies that cannot be remediated by treating
HCV by transplantation or by other directed therapy Patients with short life expectancies owing to liver disease should be managed in consultation with
an expert
aRating Class I Level AHCV hepatitis C virus1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Assessing Readiness for HCV Treatment PREP-C
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Work-up to date
Male patient
Patient Case
Cr creatinine HbA1c hemoglobin A1c
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Recommended Assessments Prior to Starting Antiviral Therapy1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
bull Blood tests ndash FIB-4 APRI or FibroTest
bull Liver elastography to measure liver stiffness ndash FibroScanreg
APRI AST to platelet ratio index FIB-4 fibrosis-4
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Patient Case Liver Disease Stage1
1 httpwwwhepatitiscuwedupageclinical-calculatorsfib-4 Accessed April 18 2017
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
aRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
bull Staging of hepatic fibrosis is essential prior to HCV treatment
bull Assessment of potential drug-drug interactions with concomitant medications is recommended prior to starting antiviral therapy Patients should also be educated on the proper administration of
medications (eg dose frequency of medicines food effect missed doses adverse effects etc) the crucial importance of adherence and the necessity for close supervision and blood tests during and after treatment
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
httpwwwhep-druginteractionsorg
Recommended Laboratory Testing1a
INR international normalized ratioaRating Class I Level C1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
Within 12 weeks prior to starting antiviral therapy
At any time prior to starting antiviral therapy
CBC INR Hepatic function panel
(albumin total and direct bilirubin alanine aminotransferase aspartate aminotransferase and alkaline phosphatase levels)
TSH if IFN is used Calculated GFR
HCV genotype and subtype Quantitative HCV RNA
(HCV viral load)
Distribution of HCV Genotypes in the United States1
1 Germer JJ et al J Clin Microbiol 2011493040-3043
HCV genotypes 1 2 and 3 are the most prevalent genotypes in the US representing gt98 of all infections
bull 62 years old bull Hypertension diabetes prior percutaneous
exposure to HCV-positive blood newly diagnosed with hepatitis C infectionndash BP controlled HbA1c 76ndash Meds simvastatin insulin lisinopril
bull HCV antibody +bull ALT 35 UL AST 21 UL Cr 11 mgdLbull Platelet count 155000mm3 Hb 136 gdL
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Multiple Highly Effective HCV Treatment Regimens Are Available1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
DAA direct-acting antiviral agents EBR elbasvir GZR grazoprevir LDV ledipasvir RVB ribavirin SOF sofosbuvir VEL velpatasvir1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
1 Falade-Nwulia O et al Ann Intern Med 2017 Mar 21 [Epub ahead of print]
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
8 weeksbull 20 patients with relapse 46bull HCV RNA lt6 million UmL 2
12 weeksbull 4 patients with relapse 06
24 weeks bull 1 patient with relapse 02
Persons With No Prior HCV Treatment
Variants in patients with virologic failure NS5A L31VMI Y93H Q30R NS5B None1 Kowdley KV et al N Engl J Med 20143701879-18882 Afdhal N et al N Engl J Med 20143701889-1898
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Chart1
Ribavirin
No Ribavirin
94
93
97
97
99
98
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
8 weeks
8 weeks
12 weeks
12 weeks
24 weeks
24 weeks
Sheet1
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Ribavirin
No Ribavirin
8 weeks
94
93
12 weeks
97
97
24 weeks
99
98
To resize chart data range drag lower right corner of range
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
618624
1 relapse2 lost to follow-up
1 withdrew consent
206210
1 relapse
117118
Velpatasvir formally GS-5816Presence of baseline RAVs did not impact SVR121 Feld JJ et al N Engl J Med 20153732599-2607
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Chart1
Series 1
SVR12
098
099
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
1a
1b
Sheet1
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Series 1
1a
98
1b
99
To resize chart data range drag lower right corner of range
Paritaprevirr-Ombitasvir + Dasabuvir (PrOD) plusmnRibavirin for HCV Genotype 1 Infection1
Genotype 1bbull 1 patient with
breakthrougha
Genotype 1a - no ribavirinbull 16 patients with virologic
failure (6 breakthrough and 10 relapse)a
Genotype 1a + ribavirinbull 2 patients with virologic
failure (1 breakthrough and 1 relapse)a
a Variants in patients with virologic failure NS3 D168V NS5A M28T and Q30R NS5B S556GPrOD paritaprevirr-ombitasvir + dasabuvir 1 Ferenci P et al N Engl J Med 20143701983-1992
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
SVR12 (95 CI) nNRange
29931695
(92-97)
14415792
(86-96)
12913199
(95-100)
1818100
(82-100)
81080
(44-98)
Lost to follow-up or discontinued early due to reasons other than virologic failure
4 3 1 0 0
Virologic breakthrough 1 1 0 0 0
Virologic relapse 12 9 1 0 2GT1a genotype 1a GT1b genotype 1b GT3 genotype 3 GT4 genotype 4 GT6 genotype 61 Zeuzem S et al Ann Intern Med 20151631-13
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
133135 112112 910 11 29 1617
Shift to EBR Shift to EBR
RAV resistance-associated variant1 Zeuzem S et al Ann Intern Med 20151631-13
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Chart1
GT1a
GT1b
SVR12
0985
1
09
1
0222
0941
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
No NS5A RAVs
No NS5A RAVs
NS5A RAVs le5-Fold
NS5A RAVs le5-Fold
NS5A RAVs gt5-Fold
NS5A RAVs gt5-Fold
Sheet1
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
GT1a
GT1b
No NS5A RAVs
99
100
NS5A RAVs le5-Fold
90
100
NS5A RAVs gt5-Fold
22
94
To resize chart data range drag lower right corner of range
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Genotype 1b bull No ribavirin 12 weeks of treatment for most patients
Genotype 1abull Guidelines increasingly favor 12 weeks or less and no ribavirin
ndash Sofosbuvir-backbone LDVSOFndash no RAS testing 8 or 12 weeks for most patients
and no ribavirin except for patient with TE and cirrhosis SOFVEL ndash no RAS testing 12 weeks for all and no ribavirin
except CTP Bndash Protease-backbone
PrOD ndash no RAS testing 12 weeks for most with 24 weeks for cirrhosis RBV for all
GZVEBR ndash Resistance testing if WT 12 weeks if NS5A RAS 16 weeks + RBV
CTB B Child-Turcotte-Pugh class B TE treatment experience WT wild type
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
Treatment-Naiumlve Genotype 2
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
a Met non-inferiority and superiority criteriaAll patients with baseline NS3 and NS5A RAVs achieved SVR12 No virologic relapse in the sofosbuvirvelpatasvir arm1 Foster GR et al N Engl J Med 20153732608-2617
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Relapse(n = 6)
Relapse(n = 2)
Relapse(n = 6)
Relapse(n = 3)
Treatment-naiumlve Treatment experienced
aribavirin
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
Chart1
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
SVR12
099
094
099
096
1
093
1
081
1
1
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Overall (134132)
Overall (134132)
No cirrhosis (10096)
No cirrhosis (10096)
Cirrhosis (1515)
Cirrhosis (1515)
No cirrhosis (1516)
No cirrhosis (1516)
Cirrhosis (44)
Cirrhosis (44)
Sheet1
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Sofosbuvirvelpatasvir
Sofosbuvir + RBV
Overall (134132)
99
94
No cirrhosis (10096)
99
96
Cirrhosis (1515)
100
93
No cirrhosis (1516)
100
81
Cirrhosis (44)
100
100
To resize chart data range drag lower right corner of range
Treatment-Naiumlve Genotype 3
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
1 Zeuzem S et al N Engl J Med 20143701993-20012 Wyles D et al 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015) Abstract 151LB 3 Nelson DR et al Hepatology 2015611127-11354 Leroy V et al J Hepatology 2016631430-1441
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
a Includes patient with evidence of G1 reinfection1 Foster GR et al N Engl J Med 20153732608-2617
Treatment-Naiumlve Genotype 4
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Treatment-Naiumlve Genotypes 5 or 6
Recommended Regimens1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed July 25 2017
GTElbasvir
grazoprevir+-ribavrin
Ledipasvirsofosbuvir
Paritaprevir ritonavir
ombitasvir dasabuvir
+- ribavirin
Simeprevir+
sofosbuvir
Sofosbuvirvelpatasvir
Daclatasvir +
sofosbuvir
1a
1b
2
3
4
5
6
Considerations for Treating HCV in the Primary Care Setting
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
bull Decide which patients you are comfortable treating Genotypes Degree of fibrosis Co-infected Renal impairment
bull Refer to a specialist for remainder of patients
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
aPotential requirements vary by insurance and state1 httpwwwhepatitiscuwedubrowseallcore-conceptsprocess-to-acquire-hcv-treatment-medications Accessed July 25 2017
bull Provider experience General medical providers may need documentation of consultation
support by experts such as through the ECHO programs
bull Proof of fibrosis stagingbull Baseline laboratory studies
eg HCV genotype HCV RNA CBC hepatic function panel
bull Clinic note documentation eg Alcohol sobriety for at least 6 months CAGE or AUDIT-C
alcohol use survey if the patient is not 100 abstinent to alcohol no injection drug use for at least 6 months drug or alcohol screening tests evaluation of psychosocial readiness for treatment justification of choice of regimen and duration of treatment
Hepatitis C Co-Pay and Patient Assistance Programs
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
1 httpwwwhepatitiscuwedupdfevaluation-treatmentaddressing-adherence-problemscore-conceptall Accessed April 18 2017
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Recommended Follow-Up After Hepatitis C Treatment1
Characteristic Follow-up
No advanced fibrosis (METAVIR stage F0-F2) bull No hepatitis C follow-up
Advanced fibrosis (METAVIR stage F3 or F4)
bull Twice-yearly ultrasound surveillance for hepatocellular carcinoma
ndash If compensated cirrhosis (F4) also test for varices using baseline endoscopy
Ongoing hepatitis C risk or unexplained hepatic dysfunction
bull Test for recurrence or reinfection with quantitative hepatitis C RNA assay
Persistently abnormal liver tests bull Test for other causes of liver disease
No virologic cure
bull Test for disease progression every 6-12 mo with hepatic function panel CBC and INR
bull Consider retreatment options
1 AASLDIDSA HCV Guidelines wwwhcvguidelinesorg Accessed April 18 2017
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
HCV Elimination in the US
ELISA enzyme-linked immunosorbent assay
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Hepatitis C is common in the United States and is a leading cause of morbidity and mortalityndash New infection among young adults due to injection narcotic usendash Prevalent infection among older adults due to exposure prior to
HCV discovery
bull Screening is recommendedndash At-risk populations should be screened initially and periodically as
behavior indicatesndash All Baby Boomers born between 1945-1965 should receive a one-
time HCV screen
bull Patients who test positive on ELISA antibody test should receive second confirmation test (HCV RNA assay)
Conclusions
ELISA enzyme-linked immunosorbent assay
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull All persons with active HCV infection should be counseledndash Prevention of liver disease
Alcohol abstinence Immunization against HAV and HBV as needed
ndash Prevention of transmission
bull All persons with active HCV infection should be considered for curative HCV treatmentndash Refer to specialist when deemed necessary (eg more advanced
liver disease)
Conclusions (Contrsquod)
HAV hepatitis A virus HBV hepatitis B virus
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Additional Case Scenarios
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Recently received cohort screening (b 1952)bull Alcohol x 40 yrs stopped with diagnosis of HCVbull No swelling jaundice GI bleeding or confusionbull Normal PEbull HTN BPHbull Tattoos in his youthbull Non-invasive assessment FIB-4 score 287 (indeterminate) Ultrasound result
borderline hepatic enlargement mild coarsening of the echotexture borderline splenomegaly (spleen at 126cm)
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
What should you do next
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Chronic lower back painbull Depression untreatedbull PTSDbull Opioid abuse ndash ~17 yr history multiple detox staysbull Stopped heroin 2 months ago has been buying
buprenorphine on the streetbull Laboratory values ASTALT ndash 96112 CoagsCBC ndash nl Hep C Ab ndash positive VLgenotype (8573421a) HIV ndash neg
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
What should you do next
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Hypertensionbull Current alcohol use (~1 pint of vodkaday)bull IV heroin ~40 years agobull Remote history of cocaine abusebull ROS fatigue RUQ painbull Additional information Viral load 1 million No coinfection WBC 8 Hct 40 plts 155 AST 84 ALT 52 INR 1 Abdominal US ndash no cirrhosis
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
What should you do next
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Medical history remarkable for injection drug use but abstinent from illicit drugs (including injection drug use) tobacco and alcohol for 10 years
bull No current medicationsbull Vital signs and PE normal
bull Additional information HCV viral load 1 million IUmL HCV genotype 1b stage-2 fibrosis up to date with all vaccines (including hepatitis A and
hepatitis B)
44-Year-Old Female Newly Diagnosed with HCV
What should you do next
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
bull Treatment-naiumlve previously refused treatment with peg-interferon (PEG-IFN) or ribavirin
bull Now expresses interest in being treated with the ldquoone-pill-a-dayrdquo regimen
bull Laboratory studies reveal HCV genotype 1a and normal liver function tests
bull Liver biopsy performed 1 year ago was significant for mild liver fibrosis viral load level obtained 2 months ago was 8 million IUmL
58-Year-Old Female 20 Year History of HCV
What should you do next
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
GrazoprevirElbasvir for 12 Weeks in Persons With HCV Genotype 1 Infection1
Impact of NS5A RAVs on GrazoprevirElbasvir Efficacy in Noncirrhotic and Cirrhotic Patients With HCV GT11
Treatment Options for HCV Genotype 1 Summary of Practical Considerations
Slide Number 59
Recommended Regimens1
SofosbuvirVelpatasvir vs Sofosbuvir + Ribavirin for 12 Weeks ASTRAL-21
Slide Number 62
Recommended Regimens1
Daclatasvir + Sofosbuvir for HCV Genotype 3 Infection1-4
SofosbuvirVelpatasvir in GT3 SVR12 by Cirrhosis and Treatment History in ASTRAL-31
Slide Number 66
Recommended Regimens1
Slide Number 68
Recommended Regimens1
Summary of Recommended Regimens for Treatment-Naiumlve Patients Without Cirrhosis1
Considerations for Treating HCV in the Primary Care Setting
Potential Requirements to Acquire HCV Treatment Medications for Patients1a
Hepatitis C Co-Pay and Patient Assistance Programs
Recommended Monitoring While on Antiviral Therapy1
Adherence to HCV Therapy1
Barriers to Adherence With Hepatitis C Therapy1
Addressing Adherence Problems Prior to HCV Treatment1
Recommended Follow-Up After Hepatitis C Treatment1
HCV Elimination in the US
Conclusions
Conclusions (Contrsquod)
Slide Number 82
64-Year-Old Male Recently Diagnosed with HCV Genotype 1a
38-Year-Old Male Diagnosed Several Years Ago with HCV Genotype 1a Treatment-Naive
62-Year-Old Male Newly Diagnosed with HCV Genotype 1b
44-Year-Old Female Newly Diagnosed with HCV
58-Year-Old Female 20 Year History of HCV
Slide Number 88
Visit us at wwwpeerviewcomUYCbull Download slides and Practice Aidsbull Watch the online version of this activity bull Join the conversation on Twitter PeerViewbull If you have any additional questions please contact
Patricia Siple at patriciasiplepeerviewcom
Thank you and have a good day
Please remember to complete and submit your Post-Test and Evaluation for CME credit
Missed anything
Slide Number 1
Slide Number 2
Slide Number 3
Global Burden of HCV Infection 150-170 Million People Infected and 500000 Deaths Annually1
Prevalence of HCV Infection in the United States1-3
Increases in HCV Infection Related to Injection Drug Use Among Persons Aged le30 Years1
Changes in Who is Starting to Inject Drugs1
HCV Infection Causes More Deaths in the US Than 60 Other Infectious Pathogens Including HIV1
Chronic HCV Infection May Lead to Chronic Liver Disease and Liver Cancer1-4
HCV Underdiagnosis and Undertreatment1
Serologic Pattern of Acute HCV Infection With Progression to Chronic Infection1
Potential Barriers to HCV Identification12
Revised HCV Screening Recommendation to Identify HCV-Infected Adults ldquoBirth Cohortrdquo12
Baby Boomers (Those Born Between 1945 and 1965) Account for 765 of HCV Cases in the US1
Screening of Baby Boomers Could Prevent More Than 120000 HCV-Related Deaths12
Other At-Risk Groups Who Should Be Screened1-3
Other At-Risk Groups Who Should Be Screened (Contrsquod)1-3
Talking to Patients About Hepatitis C Testing1
Screening Tests for HCV1-4
Recommended Testing Sequence for Identifying Current HCV Infection1
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Newly Diagnosed Patients with HCVNext Steps for the Primary Care Clinician (Contrsquod)
Slide Number 26
Guidance for the Treatment of HCV Infection
Goal of HCV Therapy1a
When and in Whom to Initiate HCV Therapy1a
Assessing Readiness for HCV Treatment PREP-C
Patient Case
Recommended Assessments Prior to Starting Antiviral Therapy1a
Liver Disease Staging Is Important but Does NOT Require Liver Biopsy
Patient Case Liver Disease Stage1
Recommended Assessments Prior to Starting Antiviral Therapy (Contrsquod)1a
Evaluating Potential Drug-Drug Interactions with Selected Antiviral Medications
Recommended Laboratory Testing1a
Distribution of HCV Genotypes in the United States1
Patient Case HCV Work-Up
Patient Case Critical Data Summary
Interferon-Based Treatments Were a Major Barrier to HCV Treatment Before October 20141
HCV Life Cycle Presents Multiple Targets for Direct Acting Antiviral Drugs1
FDA Approved Direct-Acting Antiviral Agents From Multiple Classes
Slide Number 45
Genotype 1a Without Cirrhosis Recommended Regimens1
Genotype 1a With Compensated Cirrhosis Recommended Regimens1
Genotype 1b Without Cirrhosis Recommended Regimens1
Genotype 1b With Compensated Cirrhosis Recommended Regimens1
Multiple Highly Effective HCV Treatment Regimens Are Available1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1a Infection Treated With FDA-Approved DAA Regimens1
HCV Cure Can Be Achieved in gt95 of Patients With HCV GT1b Infection Treated With FDA-Approved DAA Regimens1
HCV Eradication With the Fixed-Dose Combination of LedipasvirSofosbuvir ION-1 and ION-312
SofosbuvirVelpatasvir for 12 Weeks for Genotype 1 Infection ASTRAL-11
