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August 14, 2008 HIV and Hepatitis Chia Wang, MD

August 14, 2008 HIV and Hepatitis Chia Wang, MD. Hepatitis B and C. Chia C. Wang, MD, MS Clinical Assistant Professor of Medicine University of Washington. Outline. Quick review of Hepatitis B Staging infection Cases and Quiz---stage the infection Hepatitis C case

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August 14, 2008 HIV and Hepatitis Chia Wang, MD

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  1. August 14, 2008 HIV and Hepatitis Chia Wang, MD

  2. Hepatitis B and C Chia C. Wang, MD, MS Clinical Assistant Professor of Medicine University of Washington

  3. Outline • Quick review of Hepatitis B • Staging infection • Cases and Quiz---stage the infection • Hepatitis C case • New therapies for hepatitis C

  4. HBV Serologies

  5. Viral envelope Viral surface Viral DNA Viral core Using blood tests to stage hepatitis B infection

  6. Slide courtesy of Ray Kim, Mayo clinic HBV Markers Anti-HBs+ HBV Infection present Immunity HBsAg+ Exposure to HBV Anti-HBc+

  7. What is the significance of hepatitis B eAg? • The presence of HBeAg signifies a high circulating HBV DNA • The clearance of HBeAg is an important endpoint of treatment • Patients without HBeAg are not infectious • HBeAg is a protein secreted by the hepatitis B virus

  8. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  9. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  10. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  11. Asymptomatic Titer HBsAg HBV DNA HBeAg 32 24 0 8 4 12 20 28 36 52 100 16 Inactive chronic hepatitis B 10,000 copies/ml or 2,000 IU/ml

  12. Inactive chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg- • HBV DNA <2000 IU/ml (10,000 copies/ml)

  13. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  14. 32 52 36 28 24 20 100 12 4 8 0 16 Active eAg+ chronic hepatitis B May be symptomatic Titer HBsAg HBV DNA HBeAg 10,000 copies/ml or 2,000 IU/ml

  15. Active eAg+ chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg+ • HBV DNA >2000 IU/ml (10,000 copies/ml)

  16. 1 6 2 4 5 20 3 8 9 10 30 7 Chronic hepatitis B Sx Sx Sx Sx HBsAg Titer HBV DNA and ALT Years

  17. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  18. Core promoter and precore mutants Core promoter mutation Down regulation of eAg production Precore mutation Abolishment of eAg production

  19. 32 52 36 28 24 20 100 12 4 8 0 16 Active eAg- chronic hepatitis B May be symptomatic Titer HBsAg HBV DNA 10,000 copies/ml or 2,000 IU/ml HBeAg

  20. Active eAg- chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg- • HBV DNA >2000 IU/ml (10,000 copies/ml)

  21. Asymptomatic Titer HBsAg HBV DNA HBeAg 10,000 copies/ml or 2,000 IU/ml 12 100 52 36 24 28 36 16 52 32 4 8 28 20 32 100 20 16 24 4 8 0 0 12 Active versus inactive chronic hepatitis B May be symptomatic Titer HBsAg HBV DNA 10,000 copies/ml or 2,000 IU/ml HBeAg

  22. 3 categories of hepatitis B • Acute hepatitis B • HBsAg+, HB core IgM Ab+, HBsAb- • Resolved hepatitis B • HBsAb+, HB total core Ab+, HBsAg- • Chronic hepatitis B • Inactive hepatitis B • Active hepatitis B • eAg positive hepatitis B • eAg negative hepatitis B • Hepatitis B and cirrhosis

  23. Chronic hepatitis B and cirrhosis • Any patient with cirrhosis who is HBsAg+ and has a detectable HBV DNA should be treated

  24. Cases

  25. Case 1 • A 16 year old Ethiopian boy is being evaluated for immigration to the United States • He is HIV negative, but HBsAg positive • His liver enzymes and synthetic function are normal

  26. Which of the following tests do you need to stage his infection? • Hepatitis B core Ab • Hepatitis B surface Ab • Hepatitis B eAg and eAb • HBV DNA

  27. Case 1 lab results • Hepatitis B eAg negative • Hepatitis B eAb positive • HBV DNA 100 IU/ml

  28. What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B

  29. Which of the following is true for this patient? • He needs no treatment for his hepatitis B infection • His risk of liver cancer is lower than someone with HBeAg+ hepatitis B • His risk of liver cancer is higher than someone with HBsAb+ hepatitis B • He does not need to be screened for liver cancer, because he has inactive disease

  30. Liver Cancer

  31. AASLD recommendations for screening for liver cancer • HBsAg positive Africans starting at age 20 • HBsAg positive Asian men starting at age 40 • HBsAg positive Asian women at age 50 • Any HBsAg positive patient with cirrhosis • Any HBsAg positive patient with a family history of liver cancer • Genotype C----- start screening earlier?

  32. Case 2 • A 44 year old man with HIV is being evaluated • HIV positive • CD4 300, HIV viral load 100,000 copiesml • HBsAg positive • HBeAg negative, HBeAb positive

  33. Which of the following tests do you need to stage his infection? • Hepatitis B core Ab • Hepatitis B surface Ab • Hepatitis B eAg and eAb • HBV DNA

  34. Case 2 lab results • HBV DNA 1million IU/ml • ALT 120, AST 80 • Albumin 4.0 • Total bilirubin 1.0

  35. What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B

  36. Which of the following is true for this patient? • He needs no treatment for his hepatitis B infection • He needs a liver biopsy before deciding about hepatitis B treatment • When choosing treatment for HIV infection, antivirals that also treat Hepatitis B should be selected • Screening for liver cancer should be initiated immediately

  37. Which of the following HIV meds also treat hepatitis B? • Tenofovir • Abacavir • Lamivudine • AZT

  38. Case 3 • A 38 year old woman is found to be HIV positive and HBsAg+ • CD4 count = 250, HIV viral load 80,000 copies/ml • Hepatitis B • HBsAg + • HBeAb+ • HBV DNA 1000 IU/ml

  39. What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B

  40. Case 3 lab results • ALT=60 • AST=80 • Albumin 3.0 • T. Bilirubin 2.0 • Platelet count 80,000

  41. Gross pathology of cirrhosis Normal liver Fibrotic liver Courtesy of: http://www.meddean.luc.edu/lumen/MedEd/orfpath/cirhosis.html

  42. Which of the following is true for this patient? • She needs no treatment for his hepatitis B infection because she is in the inactive stage of infection • She is at high risk to develop liver cancer • When selecting treatment for HIV, antiviral medications should be chosen that also are effective against HBV

  43. Hepatitis C

  44. Case 4 • A 48 year old HIV-negative man is found to be Hepatitis C antibody positive • Hepatitis C viral load is 1 million IU/ml • Hepatitis C genotype is genotype 1

  45. Case 4, continued • Therapy for hepatitis C is initiated with pegylated interferon/ribavirin • At 12 weeks, hepatitis C viral load is 100,000 IU/ml • In addition, the patient suffers from terrible side effects • Nausea • Hair loss • Itching • Depression/irritability • Fatigue • Insomnia

  46. Responses to therapy • Sustained virologic response • Negative viral load 6-months after completing treatment • Relapse • -- Recurrence of viral load after initial disappearance • Non-response/partial response • -- Viral load never drops or drops by > 2 logs but never disappears

  47. RELAPSE NON-RESPONSE SUSTAINED RESPONSE Lower limit of detectable virus 6 months 12 months 18 months Hepatitis C: Patterns of Response to Treatment *

  48. Evolution of treatment for hepatitis C McHutchinson, et al. NEJM 1998;339:1485-92 Zeuzem, et al. NEJM 2000;343:1666-1672 Manns, MP et al. Lancet 2001;358:958-865

  49. Pegasys Prefilled Syringe

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