Viral Hepatitis

1. Viral Hepatitis Susanne Burger, M.D. Jacobi Medical Center North Central Bronx Hospital

2. Viral Hepatitis - Overview Type of Hepatitis

3. Case 1 A 21 y/o female college student has a 1-week h/o malaise, anorexia, nausea, and vomiting. Three weeks ago, she returned from Guatemala, where she had engaged in missionary work. PE: T 101, mild jaundice and a palpable, tender liver. Labs: HCT 48% WBC 9000/μl INR 1.0 Alk Phos 110 U/L AST 1100 U/L ALT 1700 U/L Total Bili 3.0 mg/dl

4. Which of the following laboratory tests is most likely to establish the diagnosis? (A) Ab to hepatitis B surface antigen (anti-HBs) (B) Ab to hepatitis C virus (anti-HCV) (C) Indirect hemagglutination test for Entamoeba histolytica (D) IgM antibody to hepatitis A virus (IgM anti-HAV) (E) Ebstein-Barr virus DNA

5. Hepatitis A Virus • RNA picorna virus, incubation period ~ 30 days • Transmission: close personal contact, contaminated food or water • Jaundice by age group: <6 years <10% 6-14 yrs 40-50% >14 yrs 70-80% • Rare complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis • Chronic sequilae: None • Treatment: symptomatic

6. Geographic Distribution OfHepatitis A Virus Infection

7. Reported Cases Of Hepatitis A,United States, 1952-2002 Hepatitis A Vaccine

8. Events in Hepatitis A Virus Infection

9. Hepatitis A vaccine • Highly immunogenic • 97-100% have protective levels of antibody within 1 month of receiving first dose; essentially 100% have protective levels after second dose • Post vaccination testing NOT recommended • Commercially available assay not sensitive enough to detect lower (protective) levels of vaccine-induced antibody • Provides protection even when administered following exposure to the virus – now preferred approach in between 1 – 40 years of age

10. Case 2 A 25 y/o woman is brought to the ER by her husband for yellowing of the eyes and increasing confusion and somnolence. The pt is 30 wks pregnant and just returned from visiting her parents in Africa. She has been previously healthy and only takes prenatal vitamins. She has been a social drinker until her pregnancy. PE: T 99.0 ºF, BP 90/40, HR 100, BMI 20 Exam reveals a gravid uterus and asterixis.

11. Laboratory Studies Hb 14g/dl HAV IgM neg WBC 15,000/µl HBV SAg neg PLT 450K HBV DNA neg INR 4.7 HCV Ab neg Bili (total) 12.0 mg/dL ANA neg Bili (direct) 9.0 mg/dl Anti smooth neg AST 3000 U/L Antimitochondrial Ab neg ALT 2870 U/L Alcohol neg Alk phos 400 U/L Herpes simplex virus (PCR) Alb 2.3 g/dl neg Ammonia 120 µg/dL

12. What is the most likely cause of this patient’s fulminant hepatic failure?

13. What is the most likely cause of this patient’s fulminant hepatic failure? HEV • Single most important cause of acute hepatitis in Central/S Asia and second only to HBV in Middle East and N Africa. • Transmission by fecal-oral exposure to contaminated water • In developed countries HEV related to international travel • 5 domestic US cases, likely zoonotic spread

14. Hepatitis E NEJM 2004,351;23

15. Case 3 A 30 y/o man comes to the emergency department because of a 1-week h/o of N/V, arthralgias, and dark urine. The pt has a h/o multiple sexually transmitted diseases. He drinks ~ 2 glasses of wine/d and denies the use of illicit drugs and over-the-counter prescription medications. PE reveals jaundice and a tender, enlarged liver. There are no other stigmata of chronic liver disease. Labs: HCT 49% ALT 1550 U/L WBC 11,000/μL Total Bili 6.5 mg/dL INR 1.1 Alk Phos 90 U/L AST 850 U/L

16. Which of the following laboratory studies is most likely to establish the correct diagnosis? • IgM antibody to hepatitis B core antigen (HBV cor Ab IgM) • IgG antibody to cytomegalovirus (CMV Ab IgG) • Antibody to hepatitis B surface antigen (HBV S Ab) • Antibody to hepatitis B e antigen (HBV e Ab) • IgG antibody to hepatitis A virus (HAV IgG Ab)

17. Hepatitis B • 5% of the world’s population is chronically infected with hepatitis B (~350 million cases) • Hepatitis B is the 10th leading course of death globally leading to more than 600,000 premature deaths annually • Half of all deaths are attributed to HCC

18. Routes of Transmission of HBV and Risk of Chronic Infection by Age

19. Prevalence

20. HBV vaccine efficacy

21. Acute Hepatitis B Virus Infection with Recovery - Typical Serologic Course

22. Progression to Chronic Hepatitis B Virus Infection - Typical Serologic Course

23. Natural Course of Hepatitis B

24. Stages of chronic hepatitis B: Summary Adapted from Lok AS, Hepatology. 2001;34:1225; Keeffe EB, Clin Gastroenterol Hepatol. 2004; 2;87

25. Stages of chronic hepatitis B: Summary Adapted from Lok AS, Hepatology. 2001;34:1225; Keeffe EB, Clin Gastroenterol Hepatol. 2004; 2;87

26. Stages of chronic hepatitis B: Summary Adapted from Lok AS, Hepatology. 2001;34:1225; Keeffe EB, Clin Gastroenterol Hepatol. 2004; 2;87

27. Stages of chronic hepatitis B: Summary Adapted from Lok AS, Hepatology. 2001;34:1225; Keeffe EB, Clin Gastroenterol Hepatol. 2004; 2;87

28. Stages of chronic hepatitis B: Summary Adapted from Lok AS, Hepatology. 2001;34:1225; Keeffe EB, Clin Gastroenterol Hepatol. 2004; 2;87

29. Replication cycle of Hepatitis B

30. HBV Disease Progression Liver cancer (HCC) 5 – 10%1,3 Death Chronic infection Cirrhosis Liver transplantation 30%1 Acute infection 90% of children < 5% of adults1 23% in 5 yrs2 Chronic HBV is the 5th leading cause of liver transplantation In the US4 Liver failure (decompensation) • Torres J, Gastroenterology. 2000;118:83 • Fattovich G, Hepatology. 1995;21:77 • Moyer LA, Am J prev med. 1994;10:45 • Perillo R, Hepatology. 2001;33:424

31. Therapy for chronic HBV approved by the FDA • Interferon alfa-2b (1992) • Lamivudine (1998) • Adefovir dipivoxil (2002) • Entecavir (2005) • Peginterferon alfa-2a (2005) • Talbivudine • Viread

32. Treatment endpoints in chronic HBV

33. Cumulative Probability of LAM and ADV Resistance

34. Case 4 A 34 y/o nurse reports a needle stick injury. After drawing blood from a pt, the nurse inadvertently stuck the needle into his own finger. The source pt is known to be HBsAg +. The nurse was vaccinated against HBV when he was hired 3 yrs ago. He completed the series of three injections but has never had a serologic confirmation of his response.

35. Which of the following post-exposure options is mostappropriate for this health care worker? • Administer hepatitis B immune globuline immediately and restart his immunization sequence • Check his antibody response to the hepatitis B vaccination; if antibodies are inadequate, administer hepatitis B immune globulin and restart his immunization sequence. • Check his antibody response to the hepatitis B vaccination; if antibodies are adequate, administer only hepatitis B immune globulin • (D) As the nurse has completed his hepatitis B vaccination series, no intervention is necessary

36. Case 5 A 44 y/o male IDU has a 5 day h/o malaise, N/V, RUQ discomfort, and jaundice. He takes no medications and drinks ~ 6 cans of beer/d. He has not had any sexual contact for the past 18 months and has never traveled outside the United States. Review of his medical records shows normal serum aminotransferase values despite having repeated pos tests for HBsAg. Labs 8 weeks ago: AST 24 U/L ALT 28 U/L HBV DNA undetectable HBsAg positive

37. Physical examination today discloses jaundice. The liver is mildly tender; liver span is 15 cm. Current labs: CBC normal Coags normal Alk Phos 117 U/L AST 900 U/L ALT 1050 U/L Total bili 7.8 mg/dl HBV DNA undetectable HBsAg positive HBeAg negative HbeAb positive

38. Which of the following is most likely the cause of this patient’s current clinical presentation? • Hepatitis D virus infection • Hepatitis E virus infection • Acute Ebstein-Barr virus hepatitis • Granulomatous hepatitis • Alcoholic hepatitis

39. Case 6 A 25 y/o female IDU comes to the ER because of a 10-day h/o progressive fatigue, anorexia, and abdominal discomfort. The pt uses daily heroin and drinks ~ 2-3 cans of beer/d. PE: jaundice, tender, enlarged liver Labs: CBC WNL HBsAg negative INR 1.1 Hep A Ab IgM negative Alk Phos 120 U/L Hep C Ab negative AST 1250 U/L Hep B cor Ab IgM negative ALT 2120 U/L Total bili 3.5 mg/dl

40. Which of the following tests is the most likely to establish the diagnosis? • Hep A Ab IgG • Hep B cor Ab IgG • HCV RNA • HBsAb • Antimitochondrial antibody titer

41. Diagnostic approach to hepatitis C virus infection

42. Diagnostic approach to hepatitis C virus infection

43. Diagnostic approach to hepatitis C virus infection

44. Diagnostic approach to hepatitis C virus infection

45. Diagnostic approach to hepatitis C virus infection

46. Who should be tested?CDC Recommendations • Test: • h/o IVDU • Received clotting factors before 1987, blood/organs before 1992 • Chronic hemodialysis • Evidence of liver disease • Intranasal cocaine users • h/o tattooing, body piercing • h/o STDs or multiple sex partners • Long-term steady sex partners of HCV-positive persons • Do not test: • Healthcare workers • Pregnant women • Household (non-sexual) contacts of HCV-positive persons • General population

47. Serologic Pattern of Acute HCV Infection with Progression of Chronic infection

48. Natural Course of Hepatitis C

49. Treatment of chronic Hepatitis CEvolution of HCV therapy 1990s 2004 Mc Hutchinson et al., Lindsay et al. Zeuzem et al. Manns et al. Fried et al.

50. Response Patterns 2-log decline Limit of detection SVR