HepatitisC2017

AlanWilliams,MD

*  HepatitisChistory*  HepatitisCstatistics*  BirthCohortScreening*  HepatitisCpathophysiology*  Diagnosingcirrhosis*  CurrentHepatitisCtreatment

Overview

*  TestforHepatitisB1963,HepatitisA1973*  Non-A,Non-Bhepatitis*  HepatitisCvirusidentifiedin1989*  Blooddonorscreening1990*  Effectivelyeliminatedfrombloodsupply1992*  InterferonapprovedforHepCtx1996(9%)*  Peg-Intron2001(14%)*  Peg-Intron+Ribavirin2001(47%)

HepatitisChistory

*  2011–Proteaseinhibitors–48weeks,80%*  2012–Directactingantivirals(DAA)studies,interferonfree*  2013–USPSTFrecommendsbirthcohortscreening*  2014–Harvoniapproved–12weeks(95%)-$1000/pill*  2015-present–moreoptions,lowercost*  2016–CongressallocatedmoneyforVAtotreatallveterans

HepatitisChistory

Definingtheproblemfromapopulationperspective

HepatitisCstats

IntheUnitedStates

IntheUS,PrevalenceofHCVHigherThanHIVorHBV

Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. Washington, DC: The National Academic Press; 2010

IntheUS,estimateincidenceofHCV

HCVmortality

PredictedHepatitisCmortality

HCVEpidemiologyintheUnitedStatesLastUpdated:September5th,2016Author:DavidH.Spach,MD http://www.hepatitisc.uw.edu

*  1.Allpersonsbornbetween1945and1965*  OR*  2.Allpersonswith1ormoreofthefollowingriskfactors:*  Haseverusedaneedletoinjectdrugs,evenifonceandlongago*  Hadabloodtransfusionororgantransplantbefore1992*  Isahealthcareworkerwhohadbloodexposuretomucousmembranesornon-intactskin,

orviaaneedlestickinjury*  Wasonlong-termkidneydialysis*  WasborntoamotherwhohadhepatitisCatthetime*  IsaVietnam-eraVeteran*  HadcontactwithHCV-infectedbloodtonon-intactskinortomucousmembranes*  Hastattoosorbodypiercings*  Haseversnorteddrugsandsharedequipment*  Hasliverdiseaseorabnormalliverfunctiontest*  Hasahistoryofalcoholabuse*  Hasahistoryofhemophilia*  HasasexpartnerwithhepatitisC,orhadoneinthepast*  Hashad10ormorelifetimesexpartners*  HasHIVinfection*  Hadotherpotentialblood-to-bloodexposure,duringmilitaryserviceoratanothertime*  OR*  3.Anypersonwhowishestobetested.

Whoshouldwescreen?

*  HepatitisCGenotype*  Creatinine,platelets*  Alphafetoprotein*  HepatitisBscreening*  Liverimaging*  Treatmentconsult

HepatitisC“LinktoCare”

HepatitisCantibodywillremainpositiveafterinfectionforlife

HepatitisCgenotypedistribution

*  HepatitisCvirus*  SmallenvelopedRNAvirus*  Family:Flaviviridae

*  Primarilytransmittedbyexposuretocontaminatedblood

HCVpathophysiology

ChronicLiverDisease

Synthesis:- Albumin- Coagula5onfactors

Glucosehomeostasis;glycogenolysis&gluconeogenesis

Storage:- Glycogen- Iron- Cu,Iron,vitamins

Catabolismofhormonesandotherserumproteins

Bileexcre5on

SignsofCLD

ClinicalFeaturesandDiagnosisofCirrhosis

*  Clinicalsignsofcirrhosis-subtleonsettoacutemanifestations*  Vague,nonspecificearlysignsandsymptoms*  Weakness*  Malaise*  disruptedsleep*  musclecramps*  weightloss*  Latersignsandsymptoms*  jaundice,ascites,andperipheraledema*  Resultfromhepaticcelldysfunction,portalhypertensionand

portosystemicshunting.

LaboratorytestingforCirrhosis

*  Fib-4score–estimatefibrosis–age,platelets,AST,ALT

*  MELD*  Bilirubin,INR,Cr*  Dialysis*  Sodium

*  Child-Turcotte-Pugh*  Bilirubin*  Albumin*  INR*  Ascities

TheRoleofImaginginDiagnosingCirrhosis

•  Ultrasonography,CT•  Nodularhepaticarchitecture.•  Atrophicrightlobe.•  Enlargedcaudatelobeandleftlobe.•  Difficult-to-penetrateliver.

•  Increasedechogenicity(inthepresenceoffattyinfiltration).•  Coarse,heterogeneousechotexture.•  Ascites.

•  Fibroscan–estimateoffibrosis

HepatitisCtreatment2017

*  Mostoften12weeksofonceperdaypill*  Onlya1%discontinuationrateduetosideeffects*  Basedongenotype,viralload,presenceofcirrhosis*  Priortreatment*  Presenceofresistance*  Viralloadoftenundetectableat2weeks

*  Confirmationoftreatmentsuccessistermedsustainedvirologicresponse(SVR)*  SVR=negativeviralload12weeksaftercompletingtreatment.*  Priortreatmentfailureoradvanceddiseasemayrequiremoreintensetherapy(longerduration,ribavirin,etc.)

HepatitisCtreatmentisrapidlyevolvingandimproving

HepatitisCtreatmentisrapidlyevolvingandimproving

2017 96-100%

Selecteddruginteractions

Zepatier(elpasvir/grazoprevir)•  Statins•  Carbamazepine•  PhenytoinHarvoni(ledipasvir/sofosbuvir),Epclusa(sofosbuvir/velpatasvir)•  Amiodarone•  Carbamazepine•  Phenytoin•  Anti-acids

CureImprovesOutcomesinPatientsWithHCV-AssociatedAdvancedFibrosis

In the HALT-C trial, achieving SVR significantly reduced HCV-associated complications and mortality • Median follow-up 96 months for patients with SVR, 79 months for nonresponders

Morgan TR, et al. Hepatology. 2010;52(3):833-844.

LongtermbenefitsofhepatitisCtreatment

•  Decreaseriskofdiabetes•  Loweroverallmortality•  Improvedqualityoflife•  Lowercostofhealthcare

*  HCVscreeningisrecommendedforallbabyboomers.*  Ifantibodypositive,getviralloadandgenotype.*  HepatitisCiscurable.*  Trytogetpatientsswitchedfromphenytoinorcarbamazepinebeforetreatmentreferral.

HepatitisCtakeaways

Cirrhosis:PreventiveMeasures

*  Councilpatienttoavoidalcohol*  Vaccines:Pneumonia,flu,hepatitisAandB*  Screenforesophagealvarices*  Screenforlivercancer

Questions?