care of patients post svr including those with cirrhosiscirrhosis hcv cure decreases mortality and...

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ACTHIV2019:AState-of-the-ScienceConferenceforFrontlineHealthProfessionals

ActivityCodeFM629

CareofPatientsPostSVRIncludingThosewithCirrhosis

JenniferPrice,MD,PhDAssociateProfessorofMedicine

DivisionofGastroenterologyandHepatologyUniversityofCalifornia,SanFrancisco

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LearningObjectives

Uponcompletionofthispresentation,learnersshouldbebetterableto:• RecognizetheimpactofSVRonthenaturalhistoryofHCVcirrhosis

• ExplainguidelinesforHCCsurveillanceinpatientswhohaveachievedSVR

• Identifyfactorsassociatedwithimprovementindecompensatedcirrhosispost-SVR

FacultyandPlanningCommitteeDisclosures:

PleaseconsultyourprogrambookorConferenceApp.Off-LabelDisclosure:Thefollowingoff-label/investigationaluseswillbediscussedinthispresentation:None

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HCVCareContinuesPastAchievementofSVR

Falade-NwuliaO,JHepatol,2017.

Diagnosis

Linkage tocare

Treatment

Cure

Personsatriskforinfection:§Counseling§Harmreduction(injectionandsexpractices)

§ Surveillanceforreinfection

Personswithadvancedfibrosis(stage3/4)§Counseling§Harmreduction(alcoholandobesity)

§ SurveillanceforHCC

HCVCareContinuesPastAchievementofSVR

Falade-NwuliaO,JHepatol,2017.

Diagnosis

Linkage tocare

Treatment

Cure

Personsatriskforinfection:§Counseling§Harmreduction(injectionandsexpractices)

§ Surveillanceforreinfection

Personswithadvancedfibrosis(stage3/4)§Counseling§Harmreduction(alcoholandobesity)

§ SurveillanceforHCC

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RobertS.• 47y/omanwithHCVgenotype3a,treatmentnaive• Compensatedcirrhosis

1. Hepatocellularcarcinoma(HCC)2. Liver-relatedmortality3. All-causemortality4. Alloftheabove

AchievingSVRwillreduceRobert’sriskofwhichofthefollowing?

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NaturalHistoryofCirrhosis

Compensatedcirrhosis DeathChronicliver

diseaseDecompensated

cirrhosis


Compensatedcirrhosis

Clinicalsymptoms• Ascites• Varicealbleed• Hepaticencephalopathy• Jaundice

DeathChronicliverdisease

Decompensatedcirrhosis

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Hepatocellularcarcinoma(HCC)







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1. Treatetiologyofliverdisease

ManagementofCompensatedCirrhosis

HCVCureDecreasesMortalityandLiver-RelatedComplications

SVRpatients

10-yearcum

ulative

occurren

cera

te(%)

8.9

26.0

1.9

27.4

5.1

21.8

2.1

29.9

25

20

15

10

5

0

30

All-causemortality

Liver-relatedmortalityor

livertransplant

HCC Liverfailure

MulticenterStudyof530patientswithadvancedfibrosisfollowedforamedian8.4yrs;SVR36%(interferonera)

VanderMeerAJ,JAMA,2012.

Non-SVRpatients

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RobertS.• 47y/omanwithHCVgenotype3a,treatmentnaive• Compensatedcirrhosis

RobertS.• 47y/omanwithHCVgenotype3a,treatmentnaive• Compensatedcirrhosis• TreatedwithSOF/VELx12weeksandachievedSVR12

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1. CongratulatehimonhisHCVcureanddischargehimfromclinic

2. CounselhimregardingHCVreinfectionanddischargehimfromclinic

3. CounselhimregardingHCVreinfectionandscreenforesophagealvaricesannually

4. CounselhimregardingHCVreinfectionandscreenforHCCevery6months

Whatshouldyoudonext?

1. Treatetiologyofliverdisease


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1. Treatetiologyofliverdisease2. Screen/Preventcomplicationsofcirrhosis








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HR0.28(95%CI0.22-0.36)

LargeVAstudyof22,500pts(39%withcirrhosis)

Kanwal F,Gastroenterology,2017.

SVRafterDAAsreducesbutdoesnoteliminateHCCrisk

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HR0.28(95%CI0.22-0.36)




üDAA-inducedSVRassociatedwith76%reductioninHCCrisk

HR0.28(95%CI0.22-0.36)





üAbsoluteriskofHCCpersisteddespiteSVR

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HR0.28(95%CI0.22-0.36)






üRiskofHCChighestincirrhotics:1.0-2.2%peryear

HR0.28(95%CI0.22-0.36)






üRiskofHCChighestincirrhotics:1.0-2.2%peryear

üIncreasedriskinnon-cirrhoticswith:highbaselineFIB-4,diabetes,oralcoholabuse

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Post-SVRHCCSurveillanceforPatientswithAdvancedFibrosis(≥F3)

• Every6monthabdominalultrasound+/- AFP– Alternativeimagingmodalities:quadphaseabdominalCT,contrast-enhancedMRI

• Earlydetectionincreaseslikelihoodofreceivingcurativetreatment– Resection– Locoregional therapy– Livertransplant

AASLD/IDSA.HCVguidance.March2019.SingalAG,Gastroenterology,2019.

JohnP.

• 61yearoldmalewithHCVgenotype1as/pSVR• HCVwastreatedbyanotherprovider• Tbili 0.5,AST30,ALT25,INR1.0,albumin4.1,platelets154,AFP2.6

• Abdominalultrasound:liverandspleenunremarkable• Nojaundice,GIbleeding,ascites,orencephalopathy

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1. HCCscreeningisnotneededbecausehehasnosignsorsymptomsofcirrhosis

2. Youwillrequestpre-treatmentrecordstodeterminetheneedforHCCscreening

3. YouwillgetaFibroscan orcalculateFIB-4todeterminetheneedforHCCscreening

4. HCCscreeningshouldbestartednowandcontinuedindefinitely

WhatdoyouadviseJohnaboutHCCsurveillance?

HCCSurveillanceShouldbeBasedonPre-HCVTreatment FibrosisStaging

• Accuracyofnon-invasiveestimatesoffibrosispost-SVRisunclear

• RiskofHCCinptswithpre-HCVtreatment≥F3fibrosiswhoregresstominimalfibrosispost-treatmentisunknown– PtsshouldcontinuetobemonitoredforHCCregularly

AASLD/IDSA.HCVguidance.March2019.

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SerumMarkers• AST-to-plt ratioindex(APRI)

• FIB-4

x100AST/upperlimitofnlPlateletcount(109/L)

Age(years)xAST

Plateletcount(109/L)x√ALT

Wai CT,Hepatology,2003.SterlingRK,Hepatology,2006.

https://www.hepatitisc.uw.edu/


SerumMarkers• AST-to-plt ratioindex(APRI)

• FIB-4

Non-invasiveImaging• Vibrationcontrolled

transientelastography(FibroScan®)

• Magneticresonanceelastography

x100AST/upperlimitofnlPlateletcount(109/L)

Age(years)xAST

Plateletcount(109/L)x√ALT

Wai CT,Hepatology,2003.SterlingRK,Hepatology,2006.

https://www.hepatitisc.uw.edu/

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LiverStiffnessMeasurementsImprovewithHCVTreatment

• Nearly50%ofptswith≥F3fibrosisonpre-treatmentFibroScan®willhavepost-SVRFibroScan <9.5kPa

• Earlydeclineisprobablyduetoinflammationresolution

• Decline>1yearmayrepresentfibrosisregressionbutthishasnotbeenvalidatedinpost-SVRpts

SinghS,Clin Gastroenterol Hepatol,2017.

EstimationofAdvancedFibrosiscanbeDifficultPost-SVR

• 33patientswithcirrhosisonpre-treatmentbiopsyhadpost-SVRbiopsyandFibroScan®– 13hadcirrhosisonpost-SVRbiopsy– 5(38%)hadpost-SVRFibroScan® <12kPa andwouldhavebeenmisclassifiedasnon-cirrhotic

D’Ambrosio R,JofHepatol,2013.

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EstimationofAdvancedFibrosiscanbeDifficultPost-SVR

• 33patientswithcirrhosisonpre-treatmentbiopsyhadpost-SVRbiopsyandFibroScan®– 13hadcirrhosisonpost-SVRbiopsy– 5(38%)hadpost-SVRFibroScan® <12kPa andwouldhavebeenmisclassifiedasnon-cirrhotic

• UCSFseriesof18patientswhounderwentpost-SVRbiopsyandFibroScan®– 9had≥F3fibrosisonpost-SVRbiopsy– 6(67%)hadpost-SVRFibroScan®<9.5kPa andwouldhavebeenmisclassifiedashaving<F3fibrosis

– 2developedHCCpost-SVR

D’Ambrosio R,JofHepatol,2013.KardashianA,Clin InfectDis,2018.

EsophagealVaricesScreening• Seenin45-50%ofpatientswithcirrhosis

– 40%inCPTA,60%inCPTB,80%inCPTC

• Activebleedisassociatedwith20-30%mortality• Primaryprophylaxis:non-selectivebetablockersorbandligation

Smallvarices LargevaricesNovarices

8%/year 8%/yearD’AmicoG.PortalHypertensioninthe21St Century,2004

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Diagnosis of Cirrhosis

Endoscopy

EsophagealVaricesScreening

Expertopinion


Endoscopy

No Varices


Expertopinion

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Endoscopy

No Varices

Follow-up EGD in 2-3 years*

*EGD every year in decompensated cirrhosis


Expertopinion


Endoscopy

No Varices


Small Varices



Expertopinion

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Endoscopy

No Varices


Small Varices




Expertopinion


Endoscopy

No Varices


Small Varices


Medium/Large Varices



Expertopinion

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Endoscopy

No Varices


Small Varices



Beta-blocker therapy*EGD every year in decompensated cirrhosis


Expertopinion


Endoscopy

No Varices


Small Varices



•Step-wise increase until maximally tolerated dose•Continue beta-blocker

No Contraindications



Expertopinion

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Endoscopy

No Varices


Small Varices



•Step-wise increase until maximally tolerated dose•Continue beta-blocker

No Contraindications



ContraindicationsorBeta-blocker intolerance

Endoscopic Variceal Band Ligation

Expertopinion

EGDCanbeSafelyAvoidedinLowRiskPatientswithCirrhosis

• Ptswithclinicallysignificantportalhypertension(HVPG≥10mmHg)areatriskofbleeding• Liverstiffness≥20kPa detectsclinicallysignificantportalHTN

• EGDcanbesafelyavoidedincompensatedptswith:• LS<20kPa ANDplts >150,000mm3 (Baveno VICriteria)• Thesepatientshaveverylowprobability(<5%)ofhavinghigh-riskvarices

• ThesecriteriahavebeenvalidatedinHCV+patientswhoachieveSVR

Garcia-Tsao G,AASLDGuidelines,2016.MauriceJB,JHepatol,2016.Thabut D,Gastroenterology,2019.

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• HCCsurveillanceevery6months• Varicesscreeningunlessliverstiffness<20kPa and

platelets>150



• HCCsurveillanceevery6months• Varicesscreeningunlessliverstiffness<20kPa and

platelets>150

3. Minimizeriskoffurtherliverdiseaseprogression


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• Viralinfection– HCVreinfection:counseling,harmreduction– HepatitisAandBvaccination

ModifiableRiskFactorsforLiverDiseaseProgressionPost-SVR


• Alcohol– Noamountis“safe”inpatientswithcirrhosis


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• Alcohol– Noamountis“safe”inpatientswithcirrhosis

• Metabolicfactors– Aimfornormalweight– Optimizemetabolicsyndromecomponents


• Drug-inducedliverinjury– Avoiddrugsthatmayworsenvolume/renalstatus– NSAIDSshouldbeavoidedduetoriskofrenalvasoconstrictionandrenalfailure

– Acetaminophencanbeusedif<2000mg/day– Statinsaresafeandmayhavebeneficialeffectsonliver


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https://livertox.nih.gov/

RobinT.

• 65yearoldwomanwithHCVgenotype2• Tbili 2.5,AST30,ALT20,INR1.3,albumin3.0,platelets75

• Physicalexam:BMI30,moderateascites,noencephalopathy

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1. <10%2. 15-35%3. 55-75%4. >90%

WhatarethechancesthatRobin’sdecompensatedcirrhosiswill

improveafterSVR?

Child-Turcotte-Pugh(CPT)ScoreEstimatesCirrhosisSeverity

Points1 2 3

Encephalopathy None Mild-Moderate(grade1or2)

Severe(grade3or4)

Ascites None Mild-Moderate(diureticresponsive)

Severe(diureticrefractory)

Bilirubin (mg/dL) <2 2-3 >3Albumin(g/dL) >3.5 2.8-3.5 <2.8INR <1.7 1.7-2.3 >2.3

https://www.hepatitisc.uw.edu/page/clinical-calculators/ctp

ChildA:5-6Points ChildB:7-9Points ChildC:10-15PointsCompensated Decompensated FurtherDecompensated

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Child-Turcotte-Pugh(CPT)ScoreEstimatesCirrhosisSeverity

Points1 2 3

Encephalopathy None Mild-Moderate(grade1or2)

Severe(grade3or4)

Ascites None Mild-Moderate(diureticresponsive)

Severe(diureticrefractory)

Bilirubin (mg/dL) <2 2-3 >3Albumin(g/dL) >3.5 2.8-3.5 <2.8INR <1.7 1.7-2.3 >2.3

https://www.hepatitisc.uw.edu/page/clinical-calculators/ctp

ChildA:5-6Points ChildB:7-9Points ChildC:10-15PointsCompensated Decompensated FurtherDecompensated

“Recompensation”isPossibleAfterDecompensation





X• Alcoholabstinence• HBVanti-viraltherapy

Aravinthan AD,Transpl Int,2017.VilleneuveJP,Hepatology 2000.Sponseller CA,LiverTransplan 2000.

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EvaluationofImprovementofDecompensationwithDAATherapy

• Retrospectiveanalysisfrom4trialsofSOF-basedtherapyinpatientswithdecompensatedcirrhosis– 502CPTB,120CPTC– Excluded:

• HBV,HIV,orHCC• PriorNS5Aexposure• Plts <30,liverenzymes≥10xULN,tbili >5or>10,orGFR<30

El-Sherif O,Gastroenterology,2018.

EvaluationofImprovementofDecompensationwithDAATherapy

• Retrospectiveanalysisfrom4trialsofSOF-basedtherapyinpatientswithdecompensatedcirrhosis– 502CPTB,120CPTC– Excluded:

• HBV,HIV,orHCC• PriorNS5Aexposure• Plts <30,liverenzymes≥10xULN,tbili >5or>10,orGFR<30

• Primaryendpoint:proportionachievingaclinicallymeaningfultreatmentbenefit– Sustaineddown-stagingtoCPTA


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“Recompensation”CanOccurinPatientswithChildPughBorCCirrhosiswhoAchieveSVR

Post-SVRimprovementtoCPTA:32%baselineCPTB,12%CPTC


WhatifmypatientremainsdecompensateddespiteSVR?

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IndicationsforLiverTransplant• Complicationsofcirrhosis(ChildPughBorC)

– Ascites– Portalhypertensivebleeding– Hepaticencephalopathy– Spontaneousbacterialperitonitis(SBP)– Syntheticfunctionabnormalities:bilirubin,albumin,INR

• HCCwithincriteriafortransplant• Waitinglistpriorityisbasedonliverdiseaseseverity(MELD-Na)NOTwaitingtime– PatientswithHCCgetMELD-Naexceptionpoints

ContraindicationstoLiverTransplant• Ongoingsubstanceuse

– Alcoholabstinenceof6monthsrequired• ConsiderationinpatientswithhighMELDand<6monthsobrietyvariesbytransplantcenter

– Non-marijuanarecreationaldruguse• Requireddurationofabstinencevariesbytransplantcenter

– Prescriptionnarcotics- policiesvarybycenter– Cigarettesmoking- wouldnotdelaytransplantevaluation

• Lackofsocialsupport• Severe,irreversibleco-morbidmedicalconditionsthatadverselyimpactshort-termlifeexpectancy

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HIVOrganPolicyEquity(HOPE)Act

1) HIV-infectedbeforereceivingsuchanorgan

2) ParticipatinginclinicalresearchapprovedbyanIRBuntilparticipationinsuchresearchisnolongerwarranted

• USfederallawprohibitedtransplantoforgansfromHIV-infecteddonors(NationalOrganTransplantActof1984)

• HOPEActNovember21,2013:organsinfectedwithHIVmaybetransplantedintoindividualswhoare:

HOPEconsentsandtransplants

LIVER

ConsentedN=57

KIDNEY

ConsentedN=289

HIVD-/R+N=31

HIVD+/R+N=22

HIVfalsepositiveD/R+N=23

ReceivedtransplantN=76

HIVD-/R+N=9

HIVD+/R+N=16

HIVfalsepositiveD/R+N=10

ReceivedtransplantN=35

Slidecredit:ChristineDurand

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TransplantCentersParticipatinginHOPE

Additionalinformation:https://optn.transplant.hrsa.gov/learn/professional-education/hope-act/

Slidecredit:ChristineDurand

Summary• Pre-HCVtreatmentfibrosisestimationisessentialtodeterminepost-SVRmanagementplan– Sendthework-upbeforeyoutreat

• Patientswith≥F3fibrosispre-treatmentrequireq6monthHCCsurveillance

• Patientswithcirrhosisrequirevaricesscreeningunless:– Compensated,nohistoryofvarices,liverstiffness<20kPa,ANDplatelets>150

• Focusonmodifiableriskfactorsfordiseaseprogression– CounselingandharmreductionforHCVreinfection– Vaccinations– Alcohol– Metabolicfactors:obesity,insulinresistance/diabetes

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Summary• Withmoreadvancedcirrhosis,thelikelihoodofclinicallymeaningfulbenefitofSVRdecreases– UnderscoresimportanceofdiagnosingandtreatingHCVearlierinthediseasestage

– Importantinformationforpre-treatmentcounselingandexpectationsettingforpatientswithadvancedcirrhosis

Questions?

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ACTHIV2019:AState-of-the-ScienceConferenceforFrontlineHealthProfessionals

care of patients post svr including those with cirrhosiscirrhosis hcv cure decreases mortality and...

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