Hepatitis B - seatec - Emory University

Management of Hepatitisand HIV CoinfectionDianne Weyer, FNP-BCOrientation to Adult HIV CareSoutheast AIDS and Education CenterSeptember 30, 2011

Faculty DisclosureDianne Weyer is on the speaker’s bureaufor both Bristol Myers Squibb andBoehringer Ingelheim

Hepatitis and the Alphabet Soup• Which of the following is a potential sexuallytransmitted infection leading to Hepatitis?• 1. HepatitisA• 2. Hepatitis B• 3. HepatitisC• 4. 1 & 2• 5. 2&3• 6. All of the above

THE LIVERHepatitis C Support Projectwww.hcvadvocate.org

The Liver◦ Approximately 3 lbs (men)◦ Size of a football◦ Located in upper right sidebeneaththe rib cage◦ 1.5 quarts of blood flow through it everyminuteHepatitis C SupportProjectwww.hcvadvocate.org

What Hepatitis Tests Do I Need?• Hepatitis A• HAV antibody test• Hepatitis B• HBVs Antibody (HBsAbHBsAb)• HBVc Antibody (HBcAb)• HBsAntigen• Hepatitis C• HCVantibody(HBsAg)Weyer 2011

• Transmission• contaminated food/water• oral/anal sex• High RiskHepatitis A• day care, institutions, military, MSM• Incubation period last 2 - 4 weeks• transmission occurs during this asymptomatic time• Lb Laboratory diagnosisi• HAV IgM indicates current or recent infection• HAV IgG indicates past infection or vaccinationWeyer - 2011

Hepatitis A• Infection is self-limited limited (8-12 weeks)• jaundice signals end of infectious period• vast majority recover with lifelong immunity (98-99%) 99%)• Treatment is supportive• post exposure immune globulin available• must give within 1-2 weeks of exposure• Vaccination i recommended:d• travelers to endemic areas, people with chronic liver disease(CLD) [including HCV], MSM, day care workers, foodhandlers, sewage workers, HIV infected• Prevention is key: WASH YOUR HANDS!!!CDC - 2011

CDC – Nov 10, 2010

Hepatitis B & HIV• 8 genotypes (A→H)• Genotype A• Most common in HIV/HBV in U.S.–75%• may respond best to pegIFN-α• • Genotype G• Least common in HIV/HBV in U.S. – 25%• Marker of rapid fibrosisK Lacombe and others. AIDS 20(3): 419-427, February 14, 2006.

• TransmissionHepatitis B• sexual, bloodborne, perinatal• more infectious than HIV• 90% recover with lifelong immunity• 50% among PLWHIVA• Those with chronic Hepatitis B• 10-20% will develop cirrhosis• 25% of these will decompensate• 6-15% of those with chronic disease will develophepatocellular carcinomaPeters M 9 th CROI Seattle, 2002

HBV/HIV Co-infection• Co-infected patientshave• Higher HBV DNAlevels• Lower ALT• Lower rate ofseroconversion (50%)• Higher risk of cirrhosis• IRIS• Reactivation withstopping ART• Hepatitis B vaccinationrecommended for all patientswith HIV151050Liver Mortaility by HIVand HBV Status00.81.714.1NoHBVHIVHIVHIV or only only andHBVHBVThio C et al. Lancet 2002;360:9349.

Active Hepatitis B InfectionWhich of the following set of labresults indicates active Hepatitis Binfection?a. HBsAg neg, HBsAb pos, HBeAg negb. HBSAg pos, HBsAb neg, HBeAg posc. HBsAg neg, HBsAb neg, HBeAg negd. All of the abovee. None of the above

Hepatitis B: Alphabet SoupAg – from the virus (bad)Ab – from the patient (good)E for EnvelopeC for CoreS for Surface*HBeAg – active viral replication*HBcAb – previous viral exposure*HBsAb - immunity*HBsAg – persistent virus

Acute Hepatitis B Virus Infection withRecoveryTypical Serologic CourseSymptomsHBeAganti-HBeTiterTotal anti-HBcHBsAgIgM anti-HBcanti-HBs0 4 8 12 16 20 24 28 32 36 52 100Weeks after ExposureCDC

Progression to Chronic Hepatitis B Virus InfectionTypical Serologic CourseAcute(6 months)HBeAgChronic(Years)HBsAganti-HBeTotal anti-HBcIgM anti-HBc0 4 8 12 16 20 24 28 32 36 52Weeks after ExposureCDC

Establishing a Baseline• HBeAg/anti-HBe status• HBV DNA level by PCR• ALT/AST elevation• Presence of Clinical Cirrhosis• By history/physical and lab work• Jaundice, ascites, palmar erythema, spider angiomas• Low platelets, prolonged coagulation parameters, lowalbumin• Compensated or decompensated• ?Histology from liver biopsyWeyer-2011

Hepatitis B Serologic DiagnosisHBsAgHBeAgAnti-HBsAnti-HBeAnti-HBcIgM anti-HBcHBVDNAALTAcutehepatitis B+ - + - + + + HighImmunity - + - +/- + - - NmlImmunity(infection)Immunity(vaccination)ChronicHepatitis B- + - - - - - Nml+ - + - + - +/- HighChroniccarrier+ - - + + - -orlowNmlBartlett 2009/2010

Hepatitis B Treatment in HIV/HBVHIV Therapy Indicated?CD4

Selecting Candidates for Treatment• AASLD Hepatitis B Treatment Guidelines• Hepatology February 2007• www.aasld.org• Recommendations from the HIV-Hepatitis Hepatitis B VirusInternational Panel• AIDS 2008; 22: 1399-14101410• European AIDS Clinical Society Guidelines forHBV/HIV• HIV Medicine 2008; 9: 82-8888

Risk Factors for HCC in HBV• • Cigarette smoking• • Older age• • Reversions from HBeAb+ to HBeAg+• • Presence of cirrhosis• • 30-50% HCC occur in absence of cirrhosisi• • HBV genotype C• • HCV coinfection• • Male gender• • FH of HCCAASLD Practice Guidelines; Hepatology, Vol.50, No. 3,SEP 2009

Chronic Hepatitis B: Treatment‣ Normalize transaminasesGoals‣ Eliminate/Suppress HBV replication‣ Loss of HBeAg with seroconversion to HBeAb(anti-HBe)‣ Loss of HBsAg with seroconversion to HBsAb(anti-HBs)‣ Prevent progression to end-stage liver disease(ESLD) and hepatocellular carcinoma (HCC)www.aasld.org

Medications to treat HBVMedication• Adefovir (Hepsera)• Tenofovir (VireadViread)• Lamivudine (Epivir)• Emtricitabine (Emtriva)• Entecavir (Baraclude)• Telbivudine (Tyzeka)Dosing• 10 mg po qd• 300 mg po qd• 150 mg po bid, or 300 mg po qd• 200 mg po qd• 1 mg po qd• 600 mg po qdPLUSPegylated or Standard interferongyHIV and Hepatitis Coinfections Management & Treatment Guidelines,Raymond Johnson, M.D.; 2007 Hepatitis C Support Project.2AASLD Practice Guidelines; Hepatology, Vol.50, No. 3, SEP 2009

Hepatitis B Vaccination• Seroconversion rates to primary vaccine serieslower in HIV+• May need alternative strategies in order forpatients to be protectedFonseca, Vaccine 2005; 23:2902-2908

Double Dose Vaccine in Primary SeriesStandard Dose(n=94)Double Dose(n=98)Overall seroconversion 32 (34.0%) 46 (46.9%) 0.07Stratified by CD4 countCD4

The majority of HIV-infected patientswith isolated anti-HBc are not immune toHBV infection i and should be vaccinatedwith a complete primary series of hepatitisB vaccine.Guidelines for Prevention and Treatment ofOpportunistic Infections in HIV-InfectedAdults and Adolescents - April 10, 2009

What about long standing immunity?• If vaccine recipient responds adequately to vaccine (anti-HBs > 10mIU/ml), long term protection is provided:• Immunity persists despite loss of anti-HBs• Documented protection up to 15 years, but lifelong protection islikely• Booster doses of vaccine are NOT recommended (except forselect groups, such as on hemodialysis)Fonseca, Vaccine 2005; 23:2902-2908

Another letter in theAlphabet Soup HepatitisiHEPATITIS C

CDC – Nov 10, 2010

Hepatitis C• In U.S., 4 million HCV+ → 85% chronic• If chronic → 20% cirrhotic @ 20 years• Once cirrhotic → 25% hepatocellularcarcinoma (HCC)(0.5% of total HCV+)• Alcohol (>20-50 g/d) & HIV worsen prognosis• Usually no symptoms• sometimes fatigue, RUQ ache, difficultyconcentrating or isolated d↑↑ ALT/ASTGuidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. MMWR; April 10, 2009,Vol. 58, No. RR-4

Natural HistoryAcute Hepatitis C20 0-30 yearsChronic Hepatitis75-85 %Cirrhosis 20 %Fasterprogression•older age atinfection•alcohol•HIV infection•post-transplantDi Bisceglie, Hepatology, 2000

Risk factors more common in casesthan controlsSexual risk factors• Unprotected insertive orreceptive anal intercourse• Lifetime # sex partners• Passive or active rimming• Insertive or receptive fisting• Use of sex toys• Lifetime STIs• Group sex participationp• Group sex practices• Rec/Ins UAI (unprotectedanal intercourse)• Rec/Ins fistingDrug risk factors• Rec drug use in last 12 m• Crystal meth• Ketamine• GHB• Amyl nitrites (poppers)• LSD• MDMA• Nasal route• Other route (rectal)Danta, AIDS 2007; 21:983-991)

Screening for HCV• Consider yearly HCV Ab in MSM, esp if riskfactors on previous slide present• Also think of acute HCV with any elevation ofliver enzymes, even in the absence of symptoms• Allows for early recognition i and interventioniCDC

Indications for Treatment forChronic HCV in HIV• CD4 count>350 ideal• HIV viral load

• Ongoing gsubstance useSocial Barriers• Psych history: depression, psychosis, etc.• Unstable living i situationti• Inability to afford treatments and monitoring• Poor adherence to HIV therapyWeyer - 2011

System barriers• Lack of provider expertise for treatment• No support staff• Need infrastructure• Assessing liver histology• Who does the biopsy?Weyer - 2011

Liver EnzymesTrue or falseIf liver enzymes are normal that means the liverdisease is mild and no further evaluation ortreatment is needed.d

The Pathway to a Sustained Viral ResponseSVRCompletes txStarts therapyCandidate for HCV therapyLiver diseaseAbsence of comorbiditiesInterested in treatment, viable payor sourceAppropriately referred to Hepatitis C specialistIdentified as hepatitis C positive through screening

Do you really need a liver biopsy• PROSbefore treatment?• Only reliable way to stage disease• Establish urgency of treatment• If therapy is difficult, helps NOto know how hard to pushonward• Evaluate for otherIndividualizeddiseases• CONSPatient inputRisk vs Benefit• Invasive procedure with risks• May not be availableOsborn 2008• Doesn’t change outcome• May not change decision about whether to treat• May not be readily availableM. Osborne, MD 2009

Current Standard Therapy:Pegylated Interferon + RibavirinPeg-interferon-α2b(PEG-INTRON)Linear configuration,12 kilodaltonsWeight-based: 1.5 μg/kg/wk IM for geno 2,3or 3 μg/kg/wk IM for other genosORPeg-interferon-α2a(PEGASYS)Branched chain configuration,40 kilodaltonsFixed dose of 180 μg IM per weekBoth used in combination with ribavirin 800-1200Both used in combination with ribavirin 800 1200mg divided bid depending on genotype and weight

Tue, March 15, 2011 9:33:02 PMFDA Hepatitis Update - FDA Advisoryboceprevir and telaprevir - for the treatment ofHepatitis CBoth drugs are Hepatitis C protease Inhibitorsto be used with peginterferon alfa and ribavirini ifda@service.govdelivery.comMarch 15, 2011

Two Protease Inhibitors – Genotype 1 onlyBoceprevir (BOC)Tl Telaprevir (TVR)• potent t inhibition of HCV genotype 1 replication• markedly improved SVR rates in• treatmentnaïvet t and -experienced patientst• both drugs are inhibitors of CYP3A4• Neither drug is approved for HIV/HCV coinfectionAn Update on Treatment of Genotype 1 ChronicAn Update on Treatment of Genotype 1 ChronicHepatitis C Virus Infection: 2011 PracticeGuidelines by the American Association for theStudy of Liver Diseases – August 26, 2011

Side Effects of TherapyRibavirin•Cough and dyspnea•Hemolytic anemia•Teratogenicity•Insomnia•Rash•Pruritusrit sPeg-IFN•Neuropsychiatric–Depression–Anxiety– Irritability•Neutropenia•Thrombocytopenia•AnorexiaAiNúñez. JAIDS. 2001;27:426.PDR. 2001;55:472,551,1365,2932.

Contraindications to IFN/RBV• Absolute Contraindications• pregnancy• decompensated liver disease• unstable tbl heart tdidisease• sickle cell• Relative contraindications• severe psychiatric problems• active substance abuse• untreated anemia/neutropenia• severe comorbid diseasesAASLD Guidelines: Strader et al.Hepatology 2004; 39: 1147-71

Reference material and Thanks• Melissa Osborn, MDAssistant ProfessorEmory University School of MedicineDivision of Infectious Disease

For providers:HCV Websites• www.cdc.gov/ncidod/diseases/hepatitisd/di /h i i• www.hivandhepatitis.com• www.va.gov/hepatitiscFor clients/patients:• www.thebody.com• www.hcvadvocate .org• www.hivandhepatitis.com

Helpful Resourceswww.HIVandHepatitis.comHepatitis i Info 1-800800-223223-0179NIH Consensus Statement1-888888-NIHNIH-Consensushttp://consensus.nih.gov