The Alphabet Soup of Viral Hepatitis

1. The Alphabet Soup of Viral Hepatitis Stephen J. Gluckman, M.D.

2. Hepatitis • “itis” in the “hepar”

3. Hepatitis: causes Infectious Drugs Bacterial Toxins Parasitic Vasculitis Fungal Vascular Rickettsial CHF Viral Shock EBV CMV Metabolic A,B,C,D,E,(f),G

4. Estimates of Acute and Chronic DiseaseBurden for Viral Hepatitis, United States HAV HBV HCV HDV Acute infections (x 1000)/year* 125-200 140-320 35-180 6-13 Fulminant deaths/year 100 150 ? 35 Chronic 1-1.25 3.5 0 infections million million 70,000 Chronic liver disease deaths/year 0 5,000 8-10,000 1,000 * Range based on estimated annual incidence, 1984-1994.

5. Viral Hepatitis • Transmission • Clinical disease • Diagnosis • Treatment • Prevention • Health care risk

6. HEPATITIS A VIRUS

7. GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION Anti-HAV Prevalence High High/Intermediate Intermediate Low Very Low

8. Hepatitis A: transmission • Fecal-Oral • Contaminated food and water • Person to Person • Minimal or no risk factor • Blood • Maternal-Fetal • Needle stick

9. HEPATITIS A, UNITED STATES • Most disease occurs in the context of community-wide outbreaks • Infection is also transmitted from person to person in households and extended family settings • facilitated by asymptomatic infection among children • No risk factor identified for 40%-50% of cases

10. Hepatitis A: clinical disease • Often sub-clinical • Incubation period: 2 - 6 weeks • Average 30 days • Acute, self-limited illness • Rarely fulminant • No chronic sequellae

11. EVENTS IN HEPATITIS A VIRUS INFECTION Clinical illness Infection ALT IgM IgG Viremia Response HAV in stool 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Week

12. Hepatitis A: diagnosis, treatment and prevention • Diagnosis: IgM for acute infection • IgG for past infection • Treatment: supportive • There is no specific anti-viral for hepatitis A • Prevention • Safe water • Hand washing • Pre-exposure: vaccine • Post-exposure: vaccine has replaced immune globulin

13. Health Care Workers and HAV • Minimal risk • Fecal-oral: therefore • The most important thing for the patient to do is to use the bathroom and wash hands • The most important thing for the HCW to do is wash hands • Prevention recommendation for HCW • Know your HAV antibody status • IF (+): protected • IF (-): get vaccinated

14. Hepatitis B Virus

15. Hepatitis B: transmission • Incubation period: 6 weeks to 6 months • Perinatal • The most common mode of transmission in the developing world • Sexual • The most common mode of transmission in developed countries • Parenteral • Blood products • IVDA

16. Hepatitis B: natural history Acute HBV Infection in Adults 90% 10% Chronic Resolves 30% 70% Cirrhosis HCC Benign Death

17. HBsAg Prevalence ³ 8% - High 2-7% - Intermediate < 2% - Low Geographic Distribution of Chronic HBV Infection

18. Hepatitis B: testingWhat do they all mean? • HBsAG: surface antigen • Anti-HBsAG • HBcAG: core antigen • Anti-HBcAG • IgM • IgG • HBeAG: e antigen • Anti-HBeAG • HBV DNA (viral load)

19. Hepatitis B Serology

20. Hepatitis B: diagnosis Clinical Disease ANTI-HBSAG HBSAG “Window” Titer IGM ANTI-HBCAG Time (month) Exposure

21. Hepatitis B: treatment • There are many effective options • Lamivudine (Emtricitabine) • Tenofovir • Adefovir • Entecavir • Telbivudine • Interferon

22. Hepatitis B: prevention • Pre-exposure (A MUST FOR ALL!) • Vaccine made by recombinant technology • Only HBsAG – no risk of transmission • Post-exposure • HBIG • Vaccinate

23. Eliminating HBV in the United States: Strategy • Prevent peri-natal HBV transmission • Routine vaccination of all infants • Vaccination of adolescents • Vaccination of adults in risk groups

24. Hepatitis B and Pregnancy • No need to avoid pregnancy • Neonate should get HBIG and Vaccine • No need to alter mode of delivery

25. Hepatitis B and Sexual Partners • If monogamous • Partner should be tested • If (-) vaccinate • If non-monogamous • Condoms

26. Health Care Workers and HBV • Potentially high risk from needle stick type injury • THERE IS NO REASON FOR ANY RISK! • Recommendation: Get tested (anti-HBsAG) and get immunized (or just get immunized if test not available)

27. Hepatitis BHCW Needle Stick Management • Check titer • If (+) nothing else is necessary • If (-) • History of vaccination • Give a single booster • No history of vaccination • HBIG and Vaccine

28. Hepatitis C Virus

29. Hepatitis CTransmission • IVDA • Major cause in the USA • % (+) after 1 year of using • HCV 65, HBV 50, HIV 14 • Blood transfusion • Very low risk today • Sex • Very low risk: 0.1%/yr for spouse of known positive • Higher risk with more partners • Unknown: up to 40% • HCW Needle stick: 1.8% • Perinatal: 5% • Higher with HIV co-infection • Breast Milk: no identified risk

30. Hepatitis C: natural history Acute Infection 80 % 20 % Chronic Infection Rate of Progression Resolution Slow Intermediate Rapid 30% of all with chronic infection Cirrhosis 2-5 % DEATH HCC

31. Hepatitis C: clinical course • Incubation period: 4 - 8 weeks • Acute disease generally sub-clinical or mild • Poor correlation between liver transaminases and histology • Prognosis best based on histology

32. Chronic Hepatitis C Factors Promoting Progression or Severity • Alcohol intake • Even a little alcohol intake • Miniscule amounts of alcohol intake • Age > 40 years at time of infection • HIV co-infection • Other • Male gender • Chronic HBV co-infection

33. Laboratory Pattern of Acute HCV Infection with Progression to Chronic Infection anti-HCV Exposure Symptoms +/- HCV RNA Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Years Months Time after Exposure

34. Hepatitis C • Diagnosis • IgG screen • Can take months to become positive • If IgG is (+) then must get viral load • Management • Vaccinate for Hepatitis A and B • Counsel about alcohol avoidance • Consider treatment with pegylated interferon and ribavirin • Response rates about 50% • Prevention • No vaccine • Clean needles

35. Hepatitis C and Pregnancy • No need to avoid pregnancy or breast feeding • Post exposure prophylaxis is not available • No need to alter mode of delivery • Test infant and 15-18 months

36. Hepatitis C and Sexual Partners • If one long-term steady partner • No need to change sexual practices • May choose to use condoms • If multiple partners • Remind them that they are at risk for other STD’s • Use condoms

37. Occupational Transmission of HCV • Inefficient transmission by occupational exposure • Prevalence 1-2% among health care workers • Not higher than adults in the general population • Average incidence 1.8% following needle stick from HCV-positive source • Associated with hollow-bore needles • Case reports of transmission from blood splash to eye; one from exposure to non-intact skin

38. Hepatitis CHCW Needle Stick Management • No post-exposure prophylaxis available • Check HCW HCV Antibody • If HCV antibody (-) • Recheck antibody at 3 and 6 months • OR • Check HCV PCR at 1 month • If either (+) consider treatment with pegylated interferon and ribavirin

39. Other Transmission Issues • HCV not spread by kissing, hugging, sneezing, coughing, food or water, sharing eating utensils or drinking glasses, or casual contact • Do not exclude from work, school, play, child-care or other settings based on HCV infection status

40. Hepatitis D (delta) Virus d antigen HBsAg RNA

41. Hepatitis D (HDV) • Defective pathogen that REQUIRES co-infection with hepatitis B • Simultaneous acute infection • Severe acute disease • Low risk of chronic disease • Superimposed on chronic HBV infection • Usually develop chronic hepatitis D also • Severe chronic liver disease

42. Geographic Distribution of HDV Infection Taiwan Pacific Islands HDV Prevalence High Intermediate Low Very Low No Data

43. Hepatitis D • Transmission: Sex, blood • Clinical: acute and chronic, but only in the presence of co-infection with hepatitis B • Diagnosis: serology • Treatment: treat B • Prevention: prevent B • Health care risk: unclear

44. Hepatitis E Virus

45. Geographic Distribution of Hepatitis E

46. Hepatitis E – Clinical Features • Transmission: fecal-oral • Drinking water • USA cases have history of travel to endemic areas • Incubation period • 15-60 days • Fatality 1% • *Pregnant women 15%-25% • Chronic Sequellae: none in most people • Case reports of chronic hepatitis in organ transplant recipients

47. Hepatitis E • Diagnosis: serology • Treatment: supportive • Prevention: avoid unsafe water • No evidence that IgG works • No vaccine • Health care worker risk: minimal

48. Hepatitis G • Global distribution • Spread similar to HCV • 30% homology with HCV • Not pathogenic in humans • Protective if co-infection with HIV • Decreased mortality • In vitro decreased HIV production

49. Viral Hepatitis - Summary Type of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

50. Summary • Patient • Consider Hepatitis A and B immunization for all patients • HCW Risks From a Needle Stick • HAV: minimal • HBV: 30% • HCV: 1.8% • HDV: ? • HEV: minimal • HGV: none known • (HIV: 0.3%)