Hepatitis CHepatitis CWhat’s New What’s New

Alan Kilby, M.D.Alan Kilby, M.D.

Portland Gastroenterology CenterPortland Gastroenterology CenterMaine Medical Center VTCMaine Medical Center VTC

Sept 27, 2013Sept 27, 2013

Disclosures Disclosures

Maine Medical Ctr VTC FundingMaine Medical Ctr VTC FundingSchering, Merck, VertexSchering, Merck, Vertex

Experimental Drugs DiscussedExperimental Drugs DiscussedSofosbuvir, Simeprevir, LedipasvirSofosbuvir, Simeprevir, Ledipasvir

This talk is not FDA approvedThis talk is not FDA approved

Hepatitis CHepatitis CWhat’s New What’s New 1. Test baby boomers (1945-65)1. Test baby boomers (1945-65)2. Exciting new treatments2. Exciting new treatments 2014? Sofosbuvir, Simeprevir2014? Sofosbuvir, Simeprevir

2015? One pill a day possible2015? One pill a day possible3. Fibroscan-liver fibrosis test3. Fibroscan-liver fibrosis test4. ECHO-Telemedicine Project4. ECHO-Telemedicine Project

Test Baby BoomersTest Baby BoomersBirth Cohort 1945-1965: Birth Cohort 1945-1965:

Prevalence of hep C=3.5%Prevalence of hep C=3.5%Infected in 1960’s thru 1980’sInfected in 1960’s thru 1980’s75% of hep C cases, 2-3 million75% of hep C cases, 2-3 million

Only 45% report a risk factorOnly 45% report a risk factorAt least 45% unaware; often think At least 45% unaware; often think

they are tested with routine labsthey are tested with routine labsEven with risk factors, test rate lowEven with risk factors, test rate lowAntiviral treatment rates are very lowAntiviral treatment rates are very low

Test Baby BoomersTest Baby Boomers75% Hep C Deaths: Baby Boomers75% Hep C Deaths: Baby Boomers

Liver Failure and Liver CancerLiver Failure and Liver CancerMedian Age of Death is 57 yearsMedian Age of Death is 57 yearsAfter 20 years of infection:After 20 years of infection:

20% Cirrhosis, 5% Liver mortality20% Cirrhosis, 5% Liver mortalityCirrhosis, Liver cancers, deaths Cirrhosis, Liver cancers, deaths

increase with each decadeincrease with each decade

Test Baby BoomersTest Baby BoomersCDC has Patient Information SheetCDC has Patient Information Sheet

Recommended testing:Recommended testing:1. HCV antibody1. HCV antibody2. Positive HCV antibody triggers2. Positive HCV antibody triggers HCV RNA testing.HCV RNA testing.3. I strongly encourage reflex HCV 3. I strongly encourage reflex HCV RNA testing on same sampleRNA testing on same sample

Test Baby BoomersTest Baby BoomersHCV RNA positive patientsHCV RNA positive patients

Alcohol counselingAlcohol counselingHepatitis A and B vaccinationHepatitis A and B vaccination

I recommend CBC, CMP, INR, I recommend CBC, CMP, INR, Ultrasound of Abdomen, HCV Ultrasound of Abdomen, HCV Genotype, HBsAg, HIV AbGenotype, HBsAg, HIV Ab

Evaluation for HCV treatmentEvaluation for HCV treatment

Test Baby BoomersTest Baby BoomersBenefits of Rx with SVR(Cure)Benefits of Rx with SVR(Cure)

1. Liver decompensation greatly 1. Liver decompensation greatly reducedreduced2. Liver Cancer risk reduced2. Liver Cancer risk reduced3. Study of 16,000 US Veterans 3. Study of 16,000 US Veterans demonstrated 55% reduction in all demonstrated 55% reduction in all cause mortalitycause mortality

Hepatitis CHepatitis CWhat’s NewWhat’s New

2. Exciting new treatments 2014? Sofosbuvir, Simeprevir2014? Sofosbuvir, Simeprevir2015? One pill a day possible2015? One pill a day possible

Alter et al. N Engl J Med. 1999;341;556-562.Blatt et al. J Viral Hepatitis. 2000;7:196-202.

Genotype and Viral Load in US Genotype and Viral Load in US PatientsPatients

Genotype 1 HVL

Genotype 1 LVL

Genotype 2,3 HVL

Genotype 2,3 Genotype 2,3 Low Viral Low Viral LoadLoad

49.5%49.5%

24.5%24.5%

14.7%14.7%

7.3%7.3%

Genotype Genotype 4,5,6 High 4,5,6 High Viral Load Viral Load

Genotype 4,5,6 Genotype 4,5,6 Low Viral LoadLow Viral Load2.7%2.7% 1.3%1.3%

• Peg-Interferon Weekly + Ribavirin Daily

Genotype 1 SVR=40%

48 week treatment

Wt-based ribavirin

Genotypes 2,3 SVR=80%

24 week treatment

Low dose ribavirin (800 mg)

Sustained Viral Response:Sustained Viral Response:Before 2011Before 2011

Side Effects of InterferonSide Effects of Interferon

• Flu-like symptoms– Headache– Fatigue or asthenia– Myalgia, arthralgia– Fever, chills

• Neuropsychiatric disorders

– Depression– Mood lability

• Alopecia• Thyroiditis• Nausea• Diarrhea• Injection-site reaction• Lab alterations

– Neutropenia– Anemia– Thrombocytopenia

Side Effects of RibavirinSide Effects of Ribavirin

• Hemolytic anemia

• Teratogenicity

• Cough and dyspnea

• Rash and pruritus

• Insomnia

• Anorexia

COPEGUS™ (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; 2002.

Hepatitis CHepatitis CTreatment Since 2011Treatment Since 2011Direct-Acting AntiviralsDirect-Acting Antivirals Protease InhibitorsProtease Inhibitors

Boceprevir (Victrelis)Boceprevir (Victrelis)Telaprevir (Incivek)Telaprevir (Incivek)

Triple Therapy-Triple Therapy- PEG-Interferon/Ribavirin/Protease PEG-Interferon/Ribavirin/Protease

Inhibitor for genotype 1, 24-48 Inhibitor for genotype 1, 24-48 weeksweeks

SVR for Genotype 1: 65-75%SVR for Genotype 1: 65-75%

Hepatitis CHepatitis CTreatment Since 2011Treatment Since 2011Problems with Telaprevir/BoceprevirProblems with Telaprevir/Boceprevir

1. New side effects-Rash 1. New side effects-Rash (Telaprevir), diarrhea, (Telaprevir), diarrhea, nausea; nausea; increased increased

anemiaanemia2. Poor tolerance in cirrhotics2. Poor tolerance in cirrhotics3. Drug Interactions 3. Drug Interactions (Cytochrome system): (Cytochrome system):

Hormonal contraceptives, Hormonal contraceptives, HIV, transplant drugs HIV, transplant drugs

Hepatitis CHepatitis CTreatment Since 2011Treatment Since 2011Problems with Telaprevir/Boceprevir Problems with Telaprevir/Boceprevir

triple therapytriple therapyLimited to genotype 1Limited to genotype 13x per day dosing, 6-12 pills3x per day dosing, 6-12 pillsLow barrier to drug resistanceLow barrier to drug resistancePoor efficacy: Cirrhotics, prior Poor efficacy: Cirrhotics, prior

non-responders, genotype non-responders, genotype 1a,1a,

IL28B genotype CT and TTIL28B genotype CT and TT

Hepatitis CHepatitis CTreatment: The Future Treatment: The Future

HCV Life Cycle VideoHCV Life Cycle Video

Hepatitis CHepatitis CTreatment: The Future Treatment: The Future

Sofosbuvir-Nucleotide HCV Sofosbuvir-Nucleotide HCV polymerase (NS5B) inhibitorpolymerase (NS5B) inhibitor

Once a day dosingOnce a day dosingAll genotypes treatedAll genotypes treatedMinimal side effects/drug Minimal side effects/drug interactionsinteractionsDrug resistance not observedDrug resistance not observed

Hepatitis CHepatitis CTreatment: 2014 Treatment: 2014

Likely FDA ApprovalsLikely FDA ApprovalsSofosbuvir + Ribavirin: 1Sofosbuvir + Ribavirin: 1stst Interferon-free treatment availableInterferon-free treatment available

Geno 2, 12 weeks, SVR 97%Geno 2, 12 weeks, SVR 97%Geno 3, 12 weeks, SVR 56%Geno 3, 12 weeks, SVR 56%G3 does better with 16 weeksG3 does better with 16 weeksCirrhosis-better with 16 Cirrhosis-better with 16

weeksweeks

Hepatitis CHepatitis CTreatment: 2014 Treatment: 2014

Likely FDA ApprovalsLikely FDA Approvals12 wks Sofosbuvir/Riba/PEG-IFN 12 wks Sofosbuvir/Riba/PEG-IFN

Geno 1, 4, 5, 6 SVR 90%Geno 1, 4, 5, 6 SVR 90%Cirrhosis 80%Cirrhosis 80%

Hepatitis CHepatitis CTreatment: 2014 Treatment: 2014

Likely FDA ApprovalsLikely FDA ApprovalsSimeprevir-once-a-day protease Simeprevir-once-a-day protease inhibitorinhibitorSimeprevir given for 1Simeprevir given for 1stst 12 weeks 12 weeksPEG-IFN/Ribavirin started with PEG-IFN/Ribavirin started with simeprevir and given for 24 or 48 simeprevir and given for 24 or 48 wkswksGenotype 1 SVR 83-85%Genotype 1 SVR 83-85%

Hepatitis CHepatitis CTreatment: 2015Treatment: 2015

Drugs from 2+ classes, as in HIVDrugs from 2+ classes, as in HIVIncreases efficacy and minimizes Increases efficacy and minimizes

resistanceresistanceOne Example (Many under study)One Example (Many under study)

NS5b and NS5a inhibitorNS5b and NS5a inhibitorSofosbuvir + Ledipasvir; one pill a Sofosbuvir + Ledipasvir; one pill a day; ?available 2015 day; ?available 2015

Hepatitis CHepatitis CWhat’s New What’s New

Fibroscan- A non-invasive liver Fibroscan- A non-invasive liver fibrosis testfibrosis test

FDA approvedFDA approved

FibroScan-Non-invasive test FibroScan-Non-invasive test of liver fibrosisof liver fibrosis

2.5 cm

4 cm

1 cm

Explored volume

The probe induces an elastic wave through

the liver

The velocity of the ultrasonic shear wave is a measure of elasticity (fibrosis)

FibroScan-Non-invasive FibroScan-Non-invasive test of liver fibrosistest of liver fibrosisGood accuracy in detecting cirrhosis

Combined with clinical, lab, imaging results: Will likely replace liver biopsy in detection of cirrhosis

Cirrhotics require additional monitoring

Cirrhosis: Preventive Cirrhosis: Preventive MeasuresMeasuresNo AlcoholNo Alcohol

Vaccines: Pneumonia, Flu, Vaccines: Pneumonia, Flu, Hepatitis A and BHepatitis A and B

Screen for Esophageal VaricesScreen for Esophageal Varices

Screen for Liver CancerScreen for Liver Cancer

Hepatitis CHepatitis CWhat’s New What’s New

ECHO-Telemedicine ProjectECHO-Telemedicine Project

ECHO-Telemedicine ProjectECHO-Telemedicine Project

Central site: Education/supportCentral site: Education/supportRemote sites: Treat patientsRemote sites: Treat patientsCome online together: Didactic Come online together: Didactic

session + Case Presentationssession + Case PresentationsGoal: Increase treatment at the local Goal: Increase treatment at the local

level, especially in remote areaslevel, especially in remote areasComing to Maine!Coming to Maine!

Dr. Kilby wants Dr. Kilby wants

One pill a day treatment for PCP. One pill a day treatment for PCP. Treats all patients regardless of Treats all patients regardless of genotype, severity of liver disease, genotype, severity of liver disease, presence of co-morbidities.presence of co-morbidities.

Requires minimal monitoring and Requires minimal monitoring and has few side effects, drug has few side effects, drug interactions or drug resistance.interactions or drug resistance.

Non-invasive testing for cirrhosisNon-invasive testing for cirrhosis