Hepatitis C: Pre-treatment Evaluation · 2019. 4. 17. · Risk of HBV Reactivation in with DAA’s •November 2013 –July 2016: 24 cases of HBV Reactivation •Reactivation typically

4/12/19

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ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

ACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

Hepatitis C: Pre-treatment Evaluation

Jody Gilmore, ANP-BC, MSNViral Hepatitis Coordinator

Division of Infectious DiseasesPenn Presbyterian Medical Center

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Learning Objectives

Upon completion of this presentation, learners should be better able to:– Identify HCV pre-treatment needs for patients with HIV/HCV

co-infection– Explain importance of staging liver fibrosis– Review current HCV treatment options – Identify drug-drug interactions in the treatment of HIV/HCV patients


FacultyandPlanningCommitteeDisclosuresPleaseconsultyourprogrambookortheConferenceApp.

Off-LabelDisclosureThere will be no off-label/investigational uses discussed in this presentation.

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Treatment of HIV/HCV Coinfection: Factors to Consider

• HCV workup if starting DAA:– HCV genotype– HCV RNA – Staging of liver disease– Previous DAAs– HBV status

• HIV work-up if starting/switching ART:– HIV-1 RNA level– HLA B-5701 status– CD4+ cell count– Resistance testing

• All patients– Creatinine Clearance– Non-ART, non-DAA comedications– Comorbidities

AASLD/IDSAHCVGuidelines.2018.

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Case 1: 33 yo Male with HIV and Chronic HCV Genotype 1a

• Past History: – Type 1 diabetes mellitus, insulin-dependent since age 7– HIV dx: 2012 (CD4=525 cells/mm3; HIV= 46 copies/mL)– Depression– Hepatitis C –recent screening due to elevated transaminases

• Medications:– Insulin– Elvitegravir/cobicistat//emtricitabine/tenofovir(TDF)– Sertraline



• Social History:– Works full-time, excellent private insurance– Past use IV methamphetamines- last used 2016– Denies alcohol intake, occasional marijuana– Husband also HIV+, suppressed viral load, plans to get tested

for hepatitis C

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WHENTODOHCVSCREENING?ENTRYINTOHIVCAREAND….

RecommendationforHCVTestingforPersonsWithOngoingRiskFactors

RECOMMENDED RATING

AnnualHCVtestingisrecommendedforpersonswhoinjectdrugsandforHIV-infectedmenwhohaveunprotectedsexwithmen.

PeriodictestingshouldbeofferedtootherpersonswithongoingriskfactorsforHCVexposure.

IIa,C

Available at: www.hcvguidelines.org. Accessed April 28, 2016.


Source: CDC, National Notifiable Diseases Surveillance System (NNDSS)

0

0.5

1

1.5

2

2.5

3

Repo

rted

cases/100

,000

pop

ulation

0-19yrs20-29yrs30-39yrs40-49yrs50-59yrs>60yrs

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• Physical exam:– African American– Ht 5’ 11”, Weight 165 lbs– No hepatomegaly, stigmata of liver disease

• Laboratory data:– ALT 196; AST 205– Total bilirubin 0.8; Alb 4.0; INR 1.0– HCV RNA quant 5,134,675 copies/mL



• Laboratory data (cont)– WBC 4.5; Hgb 12.9 – Platelets 325– Creat 0.86– Hemoglobin A1c- 11.3 – HBsAg (-)– anti-HBc (-)– anti-HBs (+)– HAV IgG (+)– HLA B5701 negative

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Question:What would you do next?

A. Obtain AFP

B. Stage his liver fibrosis

C. Initiate sofosbuvir/ledipasvir, Genotype 1a

D. Post-pone treatment until Hgb A1c in normal range


How to Determine Liver Fibrosis Stage

Liver Biopsy Serum Markers TransientElastographyHCV FibroSure

age (years) x AST (U/L)platelets (109/L) x ÖALT (U/L)

AST (U/L) / AST (upper limit normal)platelets (109/L)

FIB-4 =

APRI =

Liver stiffness (kPa)

Liver fibrosisSterling RK. Hepatology 2006;43:1317-25.Kirk GD et al. Clin Infect Dis 2009;48:963-72.Chou R. Ann Intern Med 2013;158:807-20.

X 100

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Liver Stiffness Measurement (LSM) Ranges in Chronic Liver Disease

METAVIRScore

F0– F1 F2 F3 F4

Liver Fibrosis

Mild Moderate Severe Cirrhosis

LSM 2.5– 7.0kPa à MildorabsentfibrosisislikelyLSM>12.5kPa à Cirrhosisislikely

2.5 7.0 9.5 12.5 12.5 kPa

Castera L, et al. J Hepatol. 2008;48(5):835-847


Vibration Controlled Transient Elastography

Strengths• Potential for assessing hepatic

steatosis with CAP• Validated technology• Excellent at determining

advanced fibrosis and cirrhosis• Low sampling error

Limitations• Cut-off uncertain• Reduced accuracy in obese

patients• Limited availability

Kim, et. al. Radiology 2013; Adams, L. Non-invasive. Determination of Advanced Diseases in NAFLD. Web. 2017Copyright © 2018 by the AASLD

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• Fibroscan results: Stiffness 8.1 kPa (F2), CAP score 253• Ultrasound of liver: no masses, hepatic steatosis • Change ART in anticipation of initiating HCV treatment

– Current ART: Elvitegravir/cobicistat//emtricitabine/tenofovir (TDF)– Not recommended with DAAs– Switch antiretrovirals to…


HIV/HCV Drug–Drug InteractionsARV(s) GLE/PIB GZR/EBR SOF/LDV SOF/VEL SOF/VEL/VOX

ATV + (RTV or COBI) X X ü* ü* X

DRV + (RTV or COBI) X X ü* ü* ü*†‡

LPV + RTV X X ü* ü* X

EFV X X ü* X X

RPV ü ü ü* ü ü

BIC ‒§ ‒§ ü† ü† ü†

DTG ü ü ü* ü ü

RAL ü ü ü ü ü

EVG/COBI/FTC/TDF ü*† X X ü* ü*†

EVG/COBI/FTC/TAF ü† X ü ü ü†

3TC/ABC ü ü ü ü ü

TAF or TDF ü ü ü* ü* ü*

DHHSGuidelines.2018.

*Monitorfortenofovir toxicityifusedwithTDF.‡Guidelinesrecommendmonitoringliverenzymesowingtolackofclinicalsafetydata

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• Discussed care with PCP/HIV provider• Changed ART to dolutegravir/lamivudine/abacavir• 4 weeks later: Wait to assess tolerance and HIV suppression

– No complaints on new regimen– Tolerating without adverse effects– HIV RNA suppressed


Factors to Consider in Selection of a DAA Regimen

• HCV genotype: determines selection of DAA …and insurance!

• Cirrhosis: duration of treatment

• Prior treatment experience (Interferon, Ribavirin, DAAs): Resistance testing

• Drug-drug interactions: statins, PPI, ART(boosted/TDF)

• Renal impairment: glecaprevir/pibrentasvir and elbasvir/grazoprevir can be used safely

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• Switch ART to dolutegravir/lamivudine/abacavir • Initiated sofosbuvir/ledipisvir, on insurer’s formulary • Treat for 8 weeks or 12 weeks?

– HCV RNA 5.1 million IU/mL– African American – HIV +– Fibrosis stage F2



Regimens Not Recommended for Patients With HIV/HCV Coinfection

NOT RECOMMENDED RATING

Ledipasvir/sofosbuvir for 8 weeks is not recommended, regardless of baseline HCV RNA level.

IIb, C

www.hcvguidelines.org

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AASLD/IDSA Recommendations for First-line HCV Treatment in HCV/HIV Coinfection

AASLD/IDSAHCVGuidelines.2018

*IfGT1awithBLNS5ARASsforEBR,12wks notrecommended;canincreasedurationto16wks withRBV(alternative).†Somedatatosupport8wks inGT1,but8wks notrecommendedinHCV/HIVcoinfection.‡Ifdecompensatedcirrhosis,donotuseHCVproteaseinhibitors.§IfBLY93HRASpresentinGT3,addRBVorconsiderSOF/VEL/VOX.‖Ifalsocirrhotic,increasedurationto12wks.

Duration,Wks NoCirrhosis CompensatedCirrhosis‡ eGFR <30mL/min

8 GLE/PIB – GLE/PIB‡‖

12 GZR/EBR,*SOF/LDV,† SOF/VEL

GLE/PIB,GZR/EBR,*SOF/LDV,SOF/VEL

GZR/EBR


12 SOF/VEL GLE/PIB,SOF/VEL§ –


12 SOF/LDV,SOF/VEL GLE/PIB,SOF/LDV,SOF/VEL

–

RegimenbyHCVGT

1,4

2,3

5,6


Drug-Drug Interactions BetweenHCV Antivirals and Other Drugs

Drugs G/P GZR/EZR SOF/LED SOF/VEL SOF/VEL/VOX

Statins

Atorvastatin Max:20mg/d Monitor

Lovastatin Monitor

Simvastatin Monitor

Rosuvastatin Max:10mg/d Max:10mg/d statin;Avoid Max:10mg/d

PravastatinDecrease

pravastatin doseby50%

Monitor

Methadone

Proton pumpinhibitors

Canbetakentogether;Max:

omeprazole20mg/d

orequivalent

TakeDAAw/food4hrs beforePPI;Max:omeprazole20 mg/d

orequivalent

Avoidcoadministrationwhen possible.

Ifnecessary:TakeDAAw/food4hrs beforePPI;Max:omeprazole20

mg/dorequivalent

hcvguidelines.org

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Followupcare:Refertoendocrinologist,repeatultrasoundofliverin6months

WeekofTreatment Lab.Results(HCVRNAQuant

copies/mL)

ALT AST

Week 0- Baseline >5millioncopies/mL ALT96 AST205

Week4 464copies/mL ALT37 AST29

Week8 Notdetected - -




RiskFactorsAssociatedwithFasterFibrosisProgressioninChronicHCV

Poynard A. Antivir Ther. 2010;15(3):281-291;Poynard, et al. Lancet. 1997;349(9055):825-832.

HCC

DiseaseStateFactors Host/ViralFactors• Male gender • Age • Obesity• Diabetes• Metabolic

syndrome• Heavy alcohol consumption• Tobacco use

LifestyleFactors

• Fibrosis stage• Inflammation grade• Persistently elevated ALT

CirrhosisNormalLiver

• HIV, HBV co-infection• Immune system

compromise• Steatosis• Iron overload• Genotype 3

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RiskofHBVReactivationinwithDAA’s• November2013– July2016:24casesofHBVReactivation

• Reactivationtypically4–8weeksafterHCVtreatmentinitiation• 2deaths,1livertransplant• BaselineHBVcharacteristics:

• 7HBsAg+andHBVDNA• 4HBsAg+undetectableHBVDNA• 3HBsAgandHBVDNAnegative;presumedisolatedcore+• 10HBVtestingnotreported/available

FDA. Drug Safety Communication. www.fda.gov/Drugs/DrugSafety/ucm522932.htm. Accessed 11/11/16.


Hepatitis B and HCVHBsAg Anti-HBs HB core AB Meaning Action

- + - Prior vaccination with immunity

No HBV infection

- + + Prior HBV infection with immunity

Monitor during DAAs

+ - + Active HBV infection Consider HBV Rx concurrent with DAAs

- - + Isolated HBV core antibody, prior

infection, no immunity

Consider HBV DNAprior to DAAs for

“occult” HBV, monitor during DAAs

Hcvguidelines.org Version May 24, 2018

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Risk of HBV reactivation during HCV treatment:Suggestions for HBV Management/Monitoring

• sAg+ and detectable HBV DNA– HBV treatment initiated 4-6 weeks prior to HCV therapy

• sAg+, undetectable HBV DNA• Close monitoring (ALT/AST q2weeks; HBV DNA monthly)• Duration?

• Isolated core +, HBV DNA negative• Close monitoring• Double dose vaccine?FDA.DrugSafetyCommunication.www.fda.gov/Drugs/DrugSafety/ucm522932.htm.Accessed11/11/16

Slide courtesy of David L Wyles, MD.


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Harm Reduction

www.hcvguidelines.org

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Take-Home Points…

• Liver fibrosis stage important pre-HCV therapy-Any method acceptableà just be sure to stage

• Consider drug-drug interactions with DAAs• DAAs efficacious, well tolerated in HIV/HCV

-genotype, cirrhosis, renal disease influence choice• Important to educate regarding reinfection

ACTHIV 2019: A State-of-the-Science Conference for Frontline Health ProfessionalsACTHIV 2019: A State-of-the-Science Conference for Frontline Health Professionals

Documents

Hepatitis C: Pre-treatment Evaluation · 2019. 4. 17. · Risk of HBV Reactivation in with DAA’s •November 2013 –July 2016: 24 cases of HBV Reactivation •Reactivation typically