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HIV and viral hepatitis co-infection Wirach Maek-a-nantawat, MD. 11 July 2011 Contents • • • • • Epidemiology Natural history Lab for diagnosis and treatment Prevention and vaccination Postexposure prophylaxis for HCP Epidemiology • High prevalence of HBV infection in Thailand Prevalence (HBV) 4.6-8% Prevalence (HIV-HBV)= 8 – 10% Genotype C (58-87%) predominating genotypes B (11-24%) and A (1-5%) 2 Subtypes: adr (80%) and adw (20%) Genotype C significantly more common in HCC patients <40 years old Zone of High HBV prevelence (>8%) Duanthanorm T, J Sci Soc Thailand 2004 Suwqnnqkarn K, et al. 2005 Tangkijvanich P, et al. World J Gastroenterol 2005 Routes of transmission of HBV coinfection - IDU, MSM (high prevalence) - Perinatal esp. young age Prevalence of HCV/HIV co-infection in Thailand USA 16%* 89%† Spain 69%* 88%† Europe 34%* 75%† Asia 26% Australia 13%* * General HIV-infected population † IVDU population •HIV/HCV infection = 7-9% • Risk factor: IDU, MSM • Among IDUs, HCV 49.5% in HIV contrast with 2.2% in non-HIV • Among Pregnant women, HCV 3.8% in HIV VS 0.3% in non-HIV • Among military conscripts, HCV 8.4% in HIV VS 2.2% in non-HIV • Genotype 3 most prevalent (70%) - Genotype 6 30% Chanbancherd P, et al SEA J Trop Med Public Health 2003 Beyrer C, et al. AIDS 2005 Jamieson DJ, et al. Infec Dis Obstet Gynecol 2008 Jatapai A, et al. Am J Trop Med Hyg 2010 Natural History of Chronic HBV Non-replicative Reactivation Hepatic Flare Natural Progression of CHB 15%–40% of CHB patients may experience disease progression Liver Cancer (HCC) 5%–10% 10%–15% in 5 yr Chronic Infection 30% Cirrhosis Liver Transplantation Death 23% in 5 yr Acute flare Liver Failure Adapted from: Fattovich, et al. Gastroenterology. 2004;127:S35-S50. Torresi, et al. Gastroenterology. 2000;118:S83-S103. Fattovich, et al. Hepatology. 1995;21:77-82. Perrillo, et al. Hepatology. 2001;33:424-432. Factors Influencing Natural History of HBV HBV viral load Age at infection Host immune status Gender HBV infection -Perinatal -IDU, MSM -Heterosexual Viral mutations Disease progression HBeAg Alcohol status use Fattovich. Semin Liver Dis. 2003;23:47-58. Chen, et al. JAMA. 2006;295:65-73. Liver cirrhosis Hepatocarcinoma Liver failure Death Co-infection with HCV or HIV Influence of HIV on HBV • Longer period of acute infection with lower rates of clearance of HBeAg • Increased serum HBV DNA viral load • Less hepatic necroinflammation in immunocompromised • Reactivation of hepatitis in asymptomatic carriers • Increased liver injury associated CD4 cell counts • Faster fibrosis cirrhosis and HCC • Higher mortality and morbidity Gilson RJ, et al. AIDS 1997 Manegold C, et al. CID 2001 Thio C, et al. Lancet 2002 Di Martino V, Gastroenterology 2002 Hepatitis B Virus – Replication Export Viral entry Uncoating ER Assembly & budding Positive strand synthesis HBsAg Nuclear import Removal of pregenome cccDNA Repair Transcription Viral accessory proteins: HBeAg and HBX 5’ 5’ 3’ 3.5 kb RNA CL Thio, Clinical Update, August 2006. 3’ 2.4/2.1 kb RNA Translation Negative strand synthesis Encapsidation HBV Treatment Landscape in 2010 Peginterferon alfa-2a Entecavir Lamivudine 1990 Interferon alfa-2b 1998 2002 Adefovir 2005 2006 Tenofovir 2008 Telbivudine Undetectable* HBV DNA After 1 Yr of Treatment Undetectable* HBV DNA (%) Not head-to-head trials; different patient populations and trial designs HBeAg Positive 100 76 80 60 60 HBeAg Negative 100 80 67 88 90 93 60-73 63 51-63 60 40-44 40 40 20 0 25 13-21 LAM ADV 20 LdT ETV TDF PegIFN 0 LAM ADV LdT *By PCR-based assay (LLD ~ 50 IU/mL) except for some LAM studies. Lok AS, et al. Hepatology. 2007;45:507-539. Lok AS, et al. Hepatology. 2009;50:661-662. ETV TDF PegIFN Cumulative Rates of Resistance With Oral Agents in Nucleos(t)ide-Naive Patients Not head-to-head trials; different patient populations and trial designs Yr 5 Yr 6 Yr 1 Yr 2 Yr 3 Yr 4 1st LAM 24% 38% 49% 67% 70% ADV 2nd LdT ETV 3rd TDF 0% 3% 11% 18% 29% 1.2% 0% 1.2% 1.2% Drug Generation 4% 0.2% 0% 17% 0.5% 0% EASL. J Hepatol. 2009;50:227-242. Tenny DJ, et al. EASL 2009. Abstract 20. Marcellin P, et al. AASLD 2009. Abstract 481. Heathcote E, et al. AASLD 2009. Abstract 483. 1.2% Why treat HBV in HIV-infected persons • Co-infection is common-10% of HIV-infected • More rapid progression of liver disease • Increased risk of liver-related mortality • Increased risk of HAART-related hepatotoxicity • ?Immune reconstitution syndrome Strategies to treat HBV and HIV • All of the following should be used with HAART • LMV naive – First line: TDF plus LMV/FTC (emtricitabine) – Other considerations • Entecavir +/- TDF • PEG-IFN • LMV experienced – First line: Add TDF to LMV – Other considerations • Entecavir 1.0 mg- resistance with LMV-R HBV • Add ADV Natural history of HCV infection HCV infection 4% 20 yr Chronic infection 70-85% Hepatoma 17% 3.6% Death 15-25 yr 15-25% Cirrhosis Resolved Extrahepatic manifectations Arthritis Glomerulonephritis Mixed cryoglobulinemia 13% Complications and Liver failure Risk Factors Associated with Transmission of HCV Transfusion or transplant from infected donor Injecting drug use Hemodialysis (yrs on treatment) Accidental injuries with needles/sharps Sexual/household exposure to anti-HCV-positive contact Multiple sex partners Birth to HCV-infected mother Impact of HIV on HCV • HIV infection worsens HCV-related liver disease (in pre-HAART era) – ALT levels higher – Fibrosis more severe – Cirrhosis, liver failure, and HCC more common – Death rates higher – Vertical HCV transmission enhanced Predictors of liver death in 812 HIV+ : age adjusted HR for liver death of risk factors for liver injury according to Cox’s proportional hazards model Infectious Diseases Dept. – Brescia, Italy Variable HR 95% CI p HCVRNA+ 10.35 2.46- 43.57 0.0014 Alcohol abuse° 2.71 1.47- 4.99 0.0014 HBsAg 2.91 1.42-5.98 0.0036 LTH* 2.25 1.02-4.98 0.0453 *LTH life threatening hepatotoxicity; time dependent covariate °Daily alcohol consumption > 80 g (men) or 60 g (women) for > 5 years Impact of HCV on HIV • Impaired Th1 function in HIV infection affects appropriate immune response to HCV • Conflicting clinical results • More rapid progression to AIDS or death for HCV genotype 1 • Increasing HIV RNA and decreasing CD4 more likely in co-infected pts HCV Treatment Rationale • HCV is curable disease. • Treatment can improve HCV outcomes – Decrease fibrosis – Increase T-cell responsiveness to HCV antigens – Decrease rate of fatal hepatocellular carcinomas • Treatment may improve HIV outcomes – Reduce hepatic toxicity of ARVs HCV Treatment Options • Pegylated Interferon-ribavirin combination therapy – Trials ongoing – Preliminary findings encouraging – Short duration for genotype 2/3 • New protease inhibitors: Boceprevir, Telaprevir (combined with pegIFN+RBV for genotype 1) – No data Host IL28B genotype and other important characteristics to help predict response to therapy Reginal distribution of IL-28B polymorphism Thomas DL, et al. Nature 2009 Access to Therapy Only a minority of HCV-HIV and HBV-HIV coinfected are treated for their hepatitis. To increase the applicability and availability of treatment especially in vulnerable groups such as in immigrants, IDUs, prisoners, people with psychiatric illnesses and people with excessive use of alcohol Lower rate of screening for hepatitis virus infection • 58% were screened for HBV and 43% screened for HCV infection in tertiary care institutes • 9.7% had HBV infection and 8.8% had HCV infection • LEE prior to the initiation of ART and undetectable HIV RNA at screening significantly associated with the finding of HBV coinfection. • The limited resources for HIV, HBV and HCV treatment & care in a resource-limited setting and unawareness of long term complications may affect rate of screening for HBV and HCV infections. Sungkanuparph S, et al. Southeast Asian J Trop Med Public Health 2008 Chotiprasitsakul D, et al. J Infect Dis Antimicrob Agents 2010 HBV Virological Assessment A. Immunological Assays 1. HBsAg/Anti-HBs 2. HBeAg/Anti-HBe 3. Anti-HBc and Anti-HBc IgM B. Molecular or nucleic acid assays 1. Quantitative HBV-DNA 2. HBV Genotyping 3. HBV Resistance evaluation (sequencing Pol) Diagnosis • HBsAg - Used as a general marker of infection. • HBsAb - Used to document recovery and/or immunity to HBV infection. • anti-HBc IgM - Marker of acute infection. • anti-HBc IgG - Past or chronic infection. • HBeAg - Active replication of virus and therefore infectiveness. • Anti-HBe - No longer viral replication. However, the patient can still be positive for HBsAg which is made by integrated HBV. • HBV-DNA - Indicating active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy. Acute Hepatitis B with Recovery Incubation Acute infection Early recovery Recovery 4-12 weeks (2-12 weeks) (12-24 weeks) (24-48 weeks) Symptoms HBeAg HBV-DNA anti-HBe Total anti-HBc Titer 0 4 anti-HBs IgM anti-HBc HBsAg 8 12 16 20 24 28 32 Weeks after Exposure 36 52 100 Typical Serologic Course in Chronic HBV Infection Incubation 4-12 weeks Acute (6 months) Chronic (Years) HBeAg anti-HBe HBV-DNA HBsAg Total anti-HBc Titer IgM anti-HBc 0 4 8 12 16 20 24 28 32 36 52 Weeks after Exposure Years Isolated antibody to HB core antigen • Frequently detected in HIV/HBV co-infection (20%-30%) • IVDU (OR 30.8, p < 0.001) and anti-HCV seropositive (OR 6.7, p = 0.002) were independent risk factors • Low anamnestic response to hepatitis B vaccination (7%) Jongjirawisan Y, et al. J Med Assoc Thai 2006 Challenges in HBsAg Serological Diagnosis • Analytic sensitivity: WHO standard 0.028–0.156IU/ml Abbott ad standard 0.18–0.73 ng/ml Abbot ay standard 0.13–0.26 ng/ml • Clinical sensitivity: 89.3–99.8% • Specificity: 97.6–100% • Surface mutants • Detection of HBV serotypes Initial serologic assessment in HBV/HIV HBV history and markers in Thailand • Significant higher ALT in genotype C than B • HBeAg significantly more frequent in genotype C than B patients (50.8 VS 30.8%,p=0.03) • Levels of HBV DNA were comparable in both genotypes • Genotype C showed higher ALT levels and more necroinflammation activity and fibrosis of liver • Progression to cirrhosis and HCC trended to be younger in genotype C • Lower response rate to IFNα therapy in genotype C • The risk of development of HCC may not be different between genotypes B and C-related chronic liver disease. Tangkijvanich P, 2004 Tangkijvanich P, 2005 Available HBV DNA Assays Artus Biotech Real Art HBV LC PCR HBV Digene Hybrid-Capture I Digene Corp. HBV Digene Hybrid-Capture II Ultra-Sensitive Digene Hybrid-Capture II Roche Molecular Systems Amplicor HBV Monitor Cobas Amplicor HBV Monitor Cobas Taqman 48 HBV Bayer Corp. Versant HBV DNA 1.0 NA Versant HBV DNA 3.0 10 102 103 104 105 106 107 108 109 1010 HBV DNA IU/mL Other HBV DNA Assays not CE marked are NAXCOR and TMA-HPA Locarnini et al., Antiv.Therapy 2004 1 HBV DNA Log copies/mL HBV DNA levels in HBV chronic carriers 10 9 8 7 6 5 4 3 2 Chronic Chronic Hepatitis B Hepatitis B HBeAgHBeAg+ Liquid Hybridization bDNA - Hybrid Capture 1 Hybrid Capture 2 Amplicor PCR Inactive carriers COBAS PCR Villeneuve JP et al. Gastroenterology 1994; Martinot –Peignoux M et al. J.Hepatol 2002; Hsu et al Hepatology 2002; Mommeja-Marin H et al. Hepatology 2003; Manno, Gastroenterology 2004 Serum HBV DNA (copies/ml) HBV mono-infection: HBV DNA and CHB 1010 109 108 107 106 105 104 103 102 In HIV co-infected ? CHB HBeAg + CHB HBeAg – ~30% Virological objective Inactive Patients Villeneuve JP et al. Gastroenterology 1994. Martinot –Peignoux M et al. J.Hepatol 2002. Hsu YS et al. Hepatology 2002. Mommeja-Marin H et al. Hepatology 2003 Management plan Antiviral Treatment Effect Antiviral treatment effect is defined as a sustained ≥1 log10 IU/ml reduction of HBV DNA from baseline levels during therapy and within 3 months of starting therapy. A decrease of ≥1 log10 IU/ml can be used to assess the early virological response. Development of resistance while on treatment is characterized by a rise of ≥1 log10 IU/ml. Primary Antiviral Treatment Failure Log HBV DNA +1.0 0.0 Antiviral Drug 1 log -1.0 -2.0 -3.0 -4.0 Secondary Antiviral Treatment Failure Log HBV DNA +1.0 0.0 Antiviral Drug 1 log -1.0 -2.0 -3.0 -4.0 1 log Demonstration of HBV Resistance in Clinical Practice with Approved Anti-HBV Drugs 1. Diagnose primary or secondary treatment failure - HBV DNA assay 2. Eliminate non-HBV-related causes of failure - drug dosage 3. Demonstrate emergence of HBV mutant during therapy - direct sequencing Two options: • The selected mutant is known to be associated with viral resistance to the drug: HBV resistance is diagnosed • The selected mutant is not known to be associated with viral resistance: further characterization is needed Antiviral Resistance Testing • Genotypic Assays • Phenotypic Assays • Virtual Phenotyping Genotypic Assays Genotyping – Analysis of the nucleic acid sequence of the region of the HBV genome that is targeted by the antiviral of interest – Identify signature sequences and/or amino acid substitutions at specific positions Assays – Direct sequencing of PCR products (population) • Full sequence of the analysed fragment • Detect any mutation – Line Probe Assay (LiPA) • Detect selected known mutations associated with drug resistance – Sequencing molecular clones (quasispecies) Genotypic Assays TRUGENE HBV 1.0 Sequences a region of 507 nucleotides – RT codons 110 – 278 – S protein codons 100 – 227 Generates a genotype report (genotypes A–H) – Based on closest match to a panel of consensus reference sequences (% homology) Generates a mutation report – A list of observed changes when compared against the closest match reference sequence, sorted by published, unpublished and silent changes INNO-LiPA HBV DR v2 • Can detect: – Wild-type – Mutant motifs for LAM resistance and compensatory mutations: • M204V/I/S, L80V/I, V/G173L, L180M – ADV resistance mutations: • A181T/V and N236T INNO-LiPA HBV DR v2 prototype strip Doutreloigne J et al., AASLD 2004 600 500 - ALT (U/L) Example of a patient treated with LAM -7 200 - -6 150 - -5 100 50 - 01 INNO-LiPA assay: Results -8 148 325 407 450 519 -4 -3 542 Codon 180 L L L/M M M M M Codon 204 M M M M M M/V V Codon 207 V V V V V V V HBV DNA log copies:mLU/ml Lamivudine 100mg/day Days YMDD (V204) mutation is detected on day 450 INNO-LiPA HBV Genotyping Identification of HBV genotypes A to G Halfon et al., EASL 2003. Antiviral Resistance Testing Phenotypic Assays Phenotyping – Measure the ability of viruses to grow in various concentrations of antiviral drugs – Could predict the clinical response to these drugs Assays – – – – Cell-culture-based Enzymatic Animal models Patient-derived clones Antiviral Resistance Testing Phenotypic Assays IC50 – Concentration of drug that inhibits 50% of viral replication Fold increase in IC50 or fold resistance – Ratio of the IC50s of the tested virus and the reference virus (wt) % viral replication 100 75 50 25 0 0.001 0.01 0.1 1 IC50 Drug Concentration 10 HBV Phenotyping Using Patient-Derived HBV Clones Patient Serum PCR Cloning Whole genome HBV clones Transient Transfection (Fitness assay) Southern analysis HepG2 • Clones reliably obtained when viral load >105 • On average, 70% of clones replicate in vitro Yang H et al., EASL 2003 Virtual Phenotyping • Matching polymerase sequences from a HBV strain to (near) identical sequences with known antiviral drug phenotype held in a large database • A “virtual” phenotype is assigned by extrapolation – providing a mean IC50 of all matched sequences – and a fold change to wild-type • If insufficient matches are found in the database – a “rules-based” interpretation is provided • Virco, SeqHepB (VIDRL) The complex natural history of HBV serological markers Acute hepatitis B Immunological Immune response tolerance Chronic hepatitis B HBeAg (+) Resolution HBV DNA (+) ALT normal/raised Spontaneous Anti-HBe (+) HBV DNA (+) ALT raised Anti-HBe (+) HBV DNA (+) ALT raised Hepatitis Immune response Viral mutations Antiviral therapy HBsAg + Anti-HBe (+) HBV DNA (low) Immune response Cirrhosis Hepatic decompensation HCC Transplant Occult HBV Infection Persistence of HBV genomes in liver tissue (± serum) by PCR-based methods in the absence of HBsAg in serum Chronic hepatitis HCC Haemodialysis pts 32.8% 63.5% 3.5 - 36 % IDU 45 % Haemophiliac pts 51.2 % Cacciola et al, NEJM 1999 Pollicino et al, Gastroenterology 2004 Minuk et al, Hepatology 2004 Besissik et al, J Hepatol 2003 Torbenson et al, Hepatology 2004 Toyoda et al, J Med Virol 2004 Chronic hepatitis B: Criteria for HCC Surveillance • Evidence supports surveillance in: Cirrhosis Family history of HCC Asian men over 40 and women over 50 years age Africans over 20 years age >40 years age with high HBV DNA and high ALT • Frequency: Every 6 months • Method: Liver ultrasound +/- alpha-fetoprotein (Bruix & Sherman 2005) Thai Guidelines for HIV/HBV coinfection • All HIV/HBV infected individuals should be evaluated: LFT, αFP, HBe Ag, (±HBV DNA) advised: - alcohol abstinence, safe sex practices, Hep A vaccination (if HAV Ab neg) • If ART or HBV treatment (+hepatitis) is indicated, the prefered regimen should include TDF/3TC or FTC as a background regimen. • If TDF, 3TC or FTC is discontinued, need close monitoring for hepatic flare or consider using adefovir dipivoxil or telbivudine for preventing hepatic flares National guidelines on HIV/AIDS diagnosis and treatment: Thailand 2010 Hepatitis B vaccination • Thailand adopted the policy for HB immunization in 1988 • Universal HB vaccination of newborns has been integrated into the national expanded programme on immunization (EPI) since 1992. • Coverage of HBV immunization in group age<18 yrold estimated 71.7%-91.3% Chongsrisawan V, et al. 2006 Hepatitis B vaccination in HIV on ART • Serologic response 54.8-71.4% • CD4 counts or NNRTI may associate with response of surface seroconversion • Coverage of vaccine among HIV infection? - lower rates of antibody response in HIV - lower levels of antibody response in HIV • Flare of HBV in cases of occult infection with isolated core antibody HIV-NAT unpublished data Paitoonpong L, et al. 2008 Hepatitis C Virus Infection Typical Serologic Course Symptoms antiHCV Titre ALT Normal 2 3 4 0 1 2 3 4 5 6 1 Years Months Time after Exposure Hepatitis C Virus Infection: Diagnosis • • • • • HCV antibody HCV viral load HCV genotype Liver function tests Liver biopsy is gold standard for assessing disease status – ALT and AST do not predict liver histology – HCV RNA does not predict liver histology or outcomes Laboratory Diagnosis • HCV antibody - generally used for diagnosis Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. • HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy. • HCV-antigen - an EIA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out. Diagnostic tests http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2011. Antibodies do not identify the presence of the virus or distinguish between acute, chronic or resolved infection HCV Diagnosis • Enzyme immunoassays ( 2nd or 3rd gen EIA) – Initial screening test for patients with liver disease – False positives in low risk patients – Occasional false negatives, esp. With HIV+ • Recombinant immunoblot assays (RIBA) – Confirmatory test if EIA positive in low risk pt • HCV RNA by PCR – Confirmatory if RIBA is “indeterminant” OraQuick HCV Rapid Test » The first Rapid HCV Test Approved for Sale in the U.S. » uses whole blood drawn from a vein, does not require laboratory processing, and returns results in about 20 minutes Detection of antibodies to HCV (anti-HCV) in HIV/HCV co-infected individuals Anti-HCV screening with 3rd generation EIA 944 HIV-negative IDU 119 anti-HCV - 1 HCV-RNA + 825 anti-HCV + 118 HCV-RNA - 559 HIV-positive IDU 547 anti-HCV + 1 HCV-RNA + 12 anti-HCV - 11 HCV-RNA - * Both anti-HCV negative HCV-RNA positive individuals became anti-HCV positive on their next visit Thio et al, J Clin Microbiol 2000;38:575-7 Qualitative Detection of HCV-RNA HCV monoinfected vs. HIV/HCV coinfected HCV mono-infection Anti-HCV positive HCV/HIV co-infection Anti-HCV positive Confirm HCV clearance in acute hepatitis Confirm HCV clearance in acute hepatitis Confirm HCV replication if other causes of liver disease Confirm HCV replication if other causes of liver disease Confirm HCV clearance at the end of treatment and follow-up Confirm HCV clearance at the end of treatment and follow-up Anti-HCV negative Anti-HCV negative Acute hepatitis (window phase) Acute hepatitis (window phase) Severe immunosuppressed patients Liver test abnormalities HCV RNA Quantification Assays 10 102 103 104 105 106 107 Cobas Amplicor HCV Monitor v2.0 (Roche) LCx HCV RNA Assay (Abbott) Versant HCV RNA 3.0 (Bayer) SuperQuant (NGI) Cobas Taqman 48 (Roche) HCV Quant ASR (Abbott) 95% of untreated hepatitis C 108 Tests for treatment monitoring Quantitative HCV-RNA HCV mono-infection HCV/HIV co-infection HCV-RNA concentration HCV-RNA concentration Before therapy (predictor of response) Before therapy (predictor of response) Week 12 after treatment initiation Week 12 after treatment initiation Co-infected pregnant mother (risk of transmission) Which role for HCV genotypes ? • Independent predictors of response to therapy • Some correlation with liver disease outcome in HIV-negative patients G3 steatosis G2 hepatitis flares Lonardo, Gastroenterology 2004; Rumi, Gut 2005 Predictors of Response Patients infected with genotype 2 and 3. low viral load (< 800,000 IU/ml). Absence of cirrhosis. Age <40 years. High ALT levels (>3x ULN). RVR at week 4 after RX Thai Guidelines for HIV/HCV co-infection • All HIV/HCV infected individuals should be encouraged to get early ART and HCV treatment • If ART is indicated, should avoid using NVP, d4T, ddI (NRTIs). • Avoid using AZT, d4T, ddI in a case treated with RBV • Should monitor AST, ALT after ART at 1 mo and every 3 mo. • Elevation of ALT ≥ 5 times ULN, investigate for HAV, HBV, alcohol, liver disease, and may discontinue ART if suspecting drug related causes. National guidelines on HIV/AIDS diagnosis and treatment: Thailand 2010 PEP for HCP Concentration of Hepatitis B Virus in Various Body Fluids High Moderate blood serum wound exudates semen vaginal fluid saliva Low/Not Detectable urine feces sweat tears breastmilk Occupational Blood-borne Exposures Relative Risk of Seroconversion with Percutanous Injury Seroconversion % 50 50% 40 30 30% 20 10 2% 0.3% 0 HIV HCV . From: CDC. MMWR 2001;50 (RR11):1-42. HBsAg+ HBeAg- HBsAg+ HBeAg+ Risk for HBV in HCP • Needle injuries with blood containing HBs Ag+ and HBe Ag+ – Developing clinical hepatitis 22-31% – Seroconversion 37-62% • Needle injuries with blood containing HBs Ag+ and HBe Ag – Developing clinical hepatitis 1-6% – Seroconversion 23-37% Werner BG, Grady GF. Ann Intern Med 1982 Hepatitis B can be prevented! If you have never had hepatitis B, you can get 3 shots . . . 1 2 3 . . . and get long lasting protection. How Is HCV Transmitted? • Infected blood – Needlestick – Needle sharing – Transfusion • ?Infected body fluids – Amniotic fluid – Breast milk – semen Risk for HCV in HCP • Percutaneous exposure from an HCV person is 1.8% • Limited data on survival of HCV in the environment • Risk for transmission from exposure to fluids other than blood expected to be low MMWR 2001 Who Should Be Tested? • Drug users • Recipients of blood products or organ transplant before 1992 • Long-term partners of infected individuals • Persons with occupational exposures • Children born to HCV-infected mothers • HIV-infected individuals Consider Testing For • Persons with tattoos or body piercing • Persons with multiple sexual partners • Tissue transplant recipients Take Home • HBV/HCV + HIV is common Screen For HBV in HIV infection • HBV vaccination for all HIV+ patients who are HBsAg• Treat HBV where indicated and carefully select your nucleotides Screen for HCV in selected patients with risks • Treat HCV where indicated/possible • Beware of hepatotoxicity and dangerous combinations