ScreeningandCurrent

ManagementStrategies:

WhoShouldBeTreatedNow?

AngieCoste,MSNCRMFNP-CTexasLiverInstitute

IntroductiontoHepatitisC

• Flavivirus•Discoveredin1989•Genotypes1-6• Estimated5-7millionpeoplewithHCVintheUSA• Leadingindicationforlivertransplantation• Leadingpredisposingfactortodevelopmentofhepatocellularcarcinoma

GlobalDistributionandPrevalenceofHCVGenotypes:Genotype1MajorUSGenotype

http://www.natap.org/2014/HCV/022114_04.htm.

MortalityDuetoChronicHCVInfectionRapidlyRising

• Age-adjustedmortalityrates(2003-2013)

• IncreasedforHCV(P<0.05)• Annualincrease:6.2%

• Decreasedforothernationallynotifiableinfectiousconditionsfrom2003to2013(P<0.05)

• HIV-relateddeaths:-42%• Pneumococcaldisease-relateddeaths:-31%• Tuberculosis-relateddeaths:-28%

• HCVdeathsin2013• 51%wereamongpersons55to64yearsofage

0

5000

10000

15000

20000

25000

30000

AnnualAge-AdjustedMortalityRates

Num

ber o

f Ann

ual D

eath

s Pr

even

ted

Year03 04 05 06 07 08 09 10 11 12 13

HCV

Other Nationally NotifiableInfectious Conditions

USmultiple-causemortalitydata(NationalCenterforHealthStatistics).

LyKN,etal.ClinInfectDis.2016;62:1287-1288.

US population with chronic HCV infection3.2 million

HCV detected1.6 million (50%)

Referred to care1.0 – 1.2 million (32%-38%)

HCV RNA test630,000 – 750,000 (20-23%)

Treated220,000 – 360,000 (7-11%)

Successfully treated170,000 – 200,000 (5-6%)

Liver biopsy380,000 – 560,000 (12%-18%)

ScreeningandLinkagetoCareRatesRemainLow

HolmbergSDetal,NewEngl JMed.2013;1859-1861.

6http://www.cdc.gov/knowmorehepatitisSmith.AASLDSF2011.,Kramer.Hepatology2011,Ly.AnInt.Med2011

CDCRecommendsAllBabyBoomersbeTestedasof

Aug16,2012

BabyBoomers:• 5xhigherprevalencethan

otherbirthcohorts

• 81%ofHCVinfectedadultsand73%ofHCVmortality

WhoShouldBeTestedForHCV?

• Allpeoplebornbetween1945and1965

• Historyofinjectedillegaldrugs

• Recipientsofclottingfactorpriorto1987

• Recipientsofbloodtransfusionsorsolidorgantransplantspriorto1992

• Useoflong-termhemodialysistreatment

• PersonswithknownexposurestohepatitisC

• AllpersonswithHIVinfection

• Patientswithsignsorsymptomsofliverdisease

• ChildrenborntomotherswhoarehepatitisCpositive

Now

McGarry LJ,etal.Hepatology. 2012;55:1344-1355;DavisG,etal.Gastroenterology. 2010;138(2):513-521.

ConsequencesofUnderdiagnosis ofHCVInfection• 33%ofundiagnosedAmericansnowhaveadvancedfibrosis/cirrhosis

HigherCancerRatesinHCVPatients:Real-WorldEvidencefromaLargeHMO• CancerdiagnosisrateishigherforHCVpatientsvs.non-HCVpatients,evenwhenexcludinglivercancer(p<0.001)

• Dataderivedfromover5,000,000patientyears

• Univariateanalysisshowsthatcancerratesweresignificantlyhigherforlivercancer,non-Hodgkinlymphomas,andtotalcancersites

0.1 1 10 100

ESOPHAGUS

STOMACH

COLON/RECTUM

LIVER

PANCREAS

MYELOMA

NON-HODGKINLYMPHOMA

HEAD/NECK

LUNG

RENAL

PROSTATE

ALLSITES(W/HCC)

ALLSITES(W/OHCC)

RATERATIO(95%CI):HCVvs.NON-HCV

CRUDEHCVvs.NON-HCVCANCERRATES

**************

*p<0.001;**p<0.005NybergAH,EASL,2015,O058.

0

5

10

15

20

25

30

35

All-Cause Mortality

HCC Liver Failure

SVR (n=192) No-SVR (n=338)

10-yearC

umulativeIncide

nceRa

te

530patientswithadvancedfibrosis,treatedwithinterferon-basedtherapy,andfollowedfor8.4years

8.9

26

5.1

21.8

2.1

29.9

SVR(Cure)AssociatedwithDecreasedAll-CauseMortality

VanderMeer,etal.JAMA.2012;308:2584.

HCVDiagnosticAlgorithm

ModifiedfromCDCGuidelinesonHep CDx,MMWR2003;52(RR03):1-16.

HCV RNA

Antibody TestEIA for anti-HCV

Active HCV InfectionMedical Evaluation

NoCurrentHCV

Infection

Spontaneous or treated

HCVGenotype&

LinkagetoCare

Born in age cohort (1945-1965) or Risk

Factors

Negative for HCV Infection

Additional Testing Recommended if:

Acute HCV suspected

WhyIsScreeningSoImportant?•UnlikeHIVorchronichepatitisB,chronichepatitisCisacurabledisease.

•Cure=sustainedviralresponse(SVR)• UndetectablehepatitisCvirus(HCVRNA)atleast12weeksaftercompletionofantiviraltherapyregimen

• Safeandeffectivetherapiesareavailable

YouIdentifyanAntibodyPositiveIndividual…NowWhat?

Pre-treatmentAssessment

Pre-treatmentLaboratoryAssessment• Basiclabsshouldinclude

• Genotype—onlyneedstobedoneonce• HCVviralloadrelativelyrecent

• Someinsurancesrequirewithin3months• Assessmentofliverfunction• Assessmentofrenalfunction(creatinine,GFR)• CBCforpatientswhowillbeonribavirin• Assessmentofliverfibrosis• Drug/alcoholscreeningifrequiredbypayors• ScreenforhepatitisB(closelyfollowthosewithHBsAg+)

• Screenforresistanceassociatedsubstitutions(RASs)

Pre-TreatmentDDIAssessment

Kiser,J. J.et al. (2013) Drug–druginteractionsduringantiviraltherapyforchronichepatitis CNat.Rev.Gastroenterol.Hepatol. doi:10.1038/nrgastro.2013.106

• Veryimportantpre-therapyassessment

• Listofprohibiteddrugsvariesdependingonregimen

• Bealertforinteractionswithcommondrugs

• Statins,protonpumpinhibitors,birthcontrolpreparations

• Noherbs!Inparticular,noSt.John’sWort

• UseonlinetoolstohelpassessDDIs

Pre-treatmentPregnancyIssues•Ribavirincontainingregimensareteratogenic

• Twocontraceptivemethods• NoOCPcontainingethinyl estradiolifusingombitasvir/paritaprevir/ritonavirwithdasabuvir

• Continuecontraceptionforupto6monthsaftercompletionoftherapy

•Ribavirin-freeregimens• PregnancyCategoryB• Avoidtherapyduringpregnancyorlactation• Recommendcontraceptionduringtherapy

ImportanceofAssessingFibrosis• Needtodeterminecirrhosisasthosepatientsinneedofadditionalscreeningandmoreurgenttreatment

• Varices• Hepatocellularcarcinoma

• Allowsforselectionofpropertreatmentplananddurationoftherapy

• Usedbysomepayersasawaytorestrictaccesstotherapy

HCVCANBECUREDINMOSTPATIENTS

0%

20%

40%

60%

80%

100%

IFN IFN IFN/R IFN/R PegIFN PegIFN/R

Sustaine

dVirologicalR

espo

nse

16%

55%

6%

34%42%

39%

6 mo 12 mo 6 mo 12 mo 12 mo

1991

1995

1998

2002

2001

Ribavirin

Peginterferon

StandardInterferon

6-12 mo

75%2011

PR + PI

PR/PI12 mo 3 mo

90%2013

PR + NI

PR/SOF

RapidAdvancesinTreatmentOptions

2015DAA

97%

DAA2-6mo

TreatmentisrecommendedforallpatientswithchronicHCVinfection,exceptthosewithshortlifeexpectanciesowingto

comorbidconditions.

AASLD-IDSATreatmentGuidelines:

MostPatientswithChronicHepatitisCShouldbeConsideredTreatmentCandidates

http://www.hcvguidelines.org (accessed March15,2017).

ClassesofOralMedicationsUsedforTreatmentNS3-4AProtease

Inhibitors(“previr”)NS5AInhibitors

(“asvir”) NS5BInhibitors: (“buvir”) Other

NucleosideAnalogues

Non-NucleosideAnalogues

Grazoprevir Daclatasvir Sofosbuvir Dasabuvir RibavirinParitaprevir ElbasvirSimeprevir Ledipasvir

OmbitasvirVelpatasvir

CombinationTherapiesGrazeprevir/Elbasvir

Paritaprevir/Ombitasvir/DasabuvirSofosbuvir/LedipasvirSofosbuvir/Velpatasvir

SummaryofCurrentlyAvailableTreatments

• Treatmentisalloraltherapyanddurationrangesfrom8-24weeksbutmostpatientstreatedwith12weeksoftherapy.

• HCVgenotypeandstageofliverdisease(non-cirrhoticvscirrhotic)dictatesduration.

• Whetheranindividualwaspreviouslytreatedisimportanttoknowinmanycases.

• Sideeffectsminimalandexcellenttolerability.• SVR>95%inmostpatientpopulations.

SpecialConsiderations

•Patientswithrenalimpairment•Patientswithcompensatedvsdecompensatedcirrhosis

•PatientswithhepatitisBcoinfection•PatientswithHCVresistanceassociatedsubstitutions(RASs)•Moretocomeinnextlectureforthesepatients

WhatHappensafterSVR?TheriskforthedevelopmentofHCC

El-Serag,etal.Hepatology. 2016;64:130-137.

• VAstudyfollowed10,817patientswhoachievedSVRbetween1999-2009

• 100developednewHCCduringfollow-up• 0.33%incidenceperyear

• Annualrisks:• 1.39%/yearinpatientswithcirrhosis• 0.95%/yearinpatientscuredafterage64

• HighriskpopulationsfordevelopingHCC• Diabetics• Genotype3

• OverallriskforthedevelopmentofHCCdecreasedwithSVRbutwasnoteliminated

HCVandHepatocellularCarcinoma•HCCscreeningneedstocontinueafterSVRinpatientswithbridgingfibrosisandcirrhosis

•Recommendedscreening:• Hepaticimagingevery6months• AFPcontroversial

• SVRdecreasesriskofHCCdevelopmentbutdoesnoteliminaterisk

Conclusions• ScreeningforHCVneedstobeincreasedinappropriatepopulationsincludingallbabyboomers

• Morethan95%oftreatedpatientscanbecuredwithcurrentlyavailabletherapies

• Refertowww.hcvguidelines.org forfurtherinformation

• HCCscreeningneedstocontinueevenafterSVRinpatientswithbridgingfibrosisandcirrhosis

• Regimensinlate-stagedevelopmentaredesignedtocuretheremainingpatients…moretocome!