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Viral Hepatitis Medicine Student Lecture
1. Viral Hepatitis Medicine Student Lecture David R Nelson, M.D. Associate Professor of Medicine Director, Hepatology and Liver Transplantation University of Florida
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3. Causes of Acute Hepatitis Acute Hepatitis Viral Hepatitis A, B/D, C, E EBV CMV & HSV Drugs Ethanol Tylenol Halothane Toxins Jamaica Bush Tea Mushrooms Vascular Hypotension Budd-Chiari Autoimmune Hepatitis Metabolic Wilson's Disease A1AT
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5. Causes of Chronic Hepatitis Abbreviations: NAFLD: nonalcoholic fatty liver disease; AIH: autoimmune hepatitis; PBC: primary biliary cirrhosis PSC: primary sclerosing cholangitis, A1AT: alpha-1 antitrypsin deficiency, HHC:hereditary hemochromotosis Chronic Hepatitis Viral Hepatitis Hep B Hep C Drugs MTX INH Amiodarone Alcohol NAFLD Autoimmune AIH PBC PSC Metabolic A1AT HHC Wilson's
6. 47% 34% 16% 3% Hepatitis A Hepatitis B Hepatitis C Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis Acute Viral Hepatitis by Type, USA: 1982-1993
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8. HAV Prevalence High Intermediate Low Very Low Global Prevalence of Hepatitis A Infection
15. Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ο³ 8% - High 2-7% - Intermediate <2% - Low > 350 million carriers (HBsAg + > 6 months) 10th cause of death (1 million / year) Cirrhosis in 20% (75 - 100 million) HCC in 5 - 10% (20 - 40 million)
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17. HBV Sources of Infection Household, 3% Other, 23% IDU, 20% Multiple sex partners, 24% Sex contact, 23% MSM, 23% Centers for Disease Control and Prevention. Hepatitis B. In: Atkinson W et al, eds. Epidemiology & Prevention of Vaccine-Preventable Diseases . 8th ed Washington DC: Public Health Foundation; 2005:191-212. Many patients do not reveal IDU as source of infection
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19. Hepatitis B - Clinical Features Incubation period Average: 60 β 90 days Range: 45 β 180 days Clinical illness (jaundice) < 5 yrs of age: <10% ο³ 5 yrs of age: 30 β 50% Acute case-fatality rate 0.5 β 1% Chronic infection < 5 yrs of age: 30 β 90% ο³ 5 yrs of age: 2 β 10% Mortality from chronic liver disease 15 β 25%
20. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Weeks after Exposure Titer IgM anti-HBc Total anti-HBc HBsAg Acute (6 months) HBeAg Chronic (Years) anti-HBe 0 4 8 12 16 20 24 28 32 36 52 Years HBV DNA
21. Interpretation of Serologic Markers Acute hepatitis B Recovery from acute hepatitis B Chronic HBeAg + disease Chronic HBeAG β disease Successful Vaccination Resistance to antiviral agents HBsAg ο (may clear) ο ο Anti-HBs ο ο Anti-HBc IgM ο Anti-HBc ο ο ο ο HBeAg ο ο Anti-HBe ο (in some cases) ο DNA (PCR if required) ο (may be only marker during window period) ο ο ο (sequence pol region)
22. Hepatitis B: Disease Progression Acute Infection Chronic Infection Cirrhosis Death 1. Torresi J et al. Gastroenterology . 2000. 2. Fattovich G et al. Hepatology . 1995. 3. Moyer LA et al. Am J Prev Med . 1994. 4. Perrillo R et al. Hepatology . 2001. 5%-10% 1 10-30% 1 23% within 5 years Liver Cancer (HCC) Chronic HBV is the 6th leading cause of liver transplantation in the US 4 Liver Transplantation Liver Failure (Decompensation) 2-6% 90% in perinatal 30-90% in children<5yrs old 5% in healthy adults Higher in HIV, immune suppressed
32. ALT Elevations Are Not Indicative of Chronic HCV Infection Inglesby TV, et al. Hepatology. 1999;29:590-596. 42 43 15 0 20 40 60 80 100 Persistently Normal ALT Intermittently Elevated ALT Persistently Elevated ALT Patients* With HCV infection (%)
33. Diagnostic Tests for HCV Infection CDC Morbidity Mortality Weekly Report. 1998;16(RR-19):1-33. NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002. Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html. Accessed April 10, 2007. Diagnostic Test Type Specifications Serologic Virologic Mode of detection Antibodies Virus Sensitivity > 95% > 98% Specificity Variable > 98% Detection postexposure 2-6 mos 2-6 wks Use Screening Confirmation
34. Molecular Virologic Assays Quantitative assays Detection cutoff > qualitative How much HCV is present? Qualitative assays High sensitivity ( ο£ 50 IU/mL) Is HCV present? Genotype assays What type of HCV is present?
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37. Prevalence of HCV Infection: United States Alter et al. N Engl J Med . 1999;341:556-562. Anti-HCV+ (%) 0 1 2 3 4 5 6 7 Age (yr) Mexican American Caucasian 3.5% 1.1% African American 3.2% 6β11 12β19 20β29 30β39 40β49 50β59 70+ 60β69
38. HCV: Disease Progression 1. NIH Consensus Development Conference Statement; March 24-26, 1997. 2. Davis GL et al. Gastroenterol Clin North Am . 1994;23:603-613. 3. Koretz RL et al. Ann Intern Med . 1993;119:110-115. 4. Takahashi M et al. Am J Gastroenterol . 1993;88:240-243. HCV infection Chronic HCV Cirrhosis Hepatic Failure Liver Cancer Liver Transplant Candidates 60-85% 1 ~20% 4 ~ 20% 3 20%-50% 2 Time: 20-30 years
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41. Improvements in Therapy of HCV Sustained Virologic Response (%) IFN 6m IFN/RBV 6m Peg-IFN/ RBV 12m IFN 12m IFN/RBV 12m Peg-IFN 12m Strader DB et al. Hepatology 2004;39:1147-1171 1991 1998 2001 2002
42. Current standard treatment duration is 48 or 24 weeks according to genotype HCV genotyping HCV-1 (4,5,6) Quantitative HCV RNA HCV-2,3 Peg-IFN + RBV 800 mg/day for 24 weeks Peg-IFN+ RBV 1000/1200 mg/day Quantitative HCV RNA at week 12 <2 log decline Stop or re-evaluate therapy ο³ 2 log decline or HCV RNA (β) 48 weeks