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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
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 • New therapies for hepatitis C
Viral envelope Viral surface Viral DNA Viral core Using blood tests to stage hepatitis B infection
Slide courtesy of Ray Kim, Mayo clinic HBV Markers Anti-HBs+ HBV Infection present Immunity HBsAg+ Exposure to HBV Anti-HBc+
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
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
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
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
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
Inactive chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg- • HBV DNA <2000 IU/ml (10,000 copies/ml)
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
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
Active eAg+ chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg+ • HBV DNA >2000 IU/ml (10,000 copies/ml)
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
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
Core promoter and precore mutants Core promoter mutation Down regulation of eAg production Precore mutation Abolishment of eAg production
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
Active eAg- chronic hepatitis B • HBsAg+ • HB total core Ab+ • HBeAg- • HBV DNA >2000 IU/ml (10,000 copies/ml)
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
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
Chronic hepatitis B and cirrhosis • Any patient with cirrhosis who is HBsAg+ and has a detectable HBV DNA should be treated
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
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
Case 1 lab results • Hepatitis B eAg negative • Hepatitis B eAb positive • HBV DNA 100 IU/ml
What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B
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
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?
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
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
Case 2 lab results • HBV DNA 1million IU/ml • ALT 120, AST 80 • Albumin 4.0 • Total bilirubin 1.0
What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B
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
Which of the following HIV meds also treat hepatitis B? • Tenofovir • Abacavir • Lamivudine • AZT
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
What stage of hepatitis B is the patient in? • Chronic inactive hepatitis B • Chronic eAg positive hepatitis B • Chronic eAg negative hepatitis B
Case 3 lab results • ALT=60 • AST=80 • Albumin 3.0 • T. Bilirubin 2.0 • Platelet count 80,000
Gross pathology of cirrhosis Normal liver Fibrotic liver Courtesy of: http://www.meddean.luc.edu/lumen/MedEd/orfpath/cirhosis.html
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
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
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
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
RELAPSE NON-RESPONSE SUSTAINED RESPONSE Lower limit of detectable virus 6 months 12 months 18 months Hepatitis C: Patterns of Response to Treatment *
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