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Hepatitis B

Hepatitis B. Patricia D. Jones, M.D. November 13, 2009. Hepatitis B. Prototype member of the Hepadnaviridae family DNA virus Outer lipoprotein envelope with 3 glycoproteins – Hep B surface antigens (HBsAg) Viral nucleocapsid protein - Hep B core antigen (HBcAg)

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Hepatitis B

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  1. Hepatitis B Patricia D. Jones, M.D. November 13, 2009

  2. Hepatitis B • Prototype member of the Hepadnaviridae family • DNA virus • Outer lipoprotein envelope with 3 glycoproteins – Hep B surface antigens (HBsAg) • Viral nucleocapsid protein - Hep B core antigen (HBcAg) • Soluble nucleocapsid protein-Hepatitis B e antigen (HBeAg) http://pathmicro.med.sc.edu/virol/hep-b5.jpg

  3. Epidemiology • Worldwide: • Affects 350-400 million persons • Endemic areas: Asia, Africa • 1 million worldwide deaths per year • Acquired perinatally and in childhood • United States: • Affects 1.25 million persons • 4000-5000 deaths per year • Acquired via sexual activity, then IVDU and occupational exposure http://liver.stanford.edu/images/education/world_incidence.jpg

  4. Primary Infection • Incubation Period 4-10 weeks • During the prodromal period, patient may have a serum sickness-like syndrome. • Constitutional symptoms, anorexia, nausea, RUQ discomfort and jaundice. • 30 % develop icteric hepatitis. • 70% develop anicteric or subclinical hepatitis. • 0.5-1% develop fulminant liver failure. • Symptoms and jaundice disappear in 1-3 months, though fatigue may persist.

  5. Infection in Children vs. Adults • Children • In neonates, the immature immune system does not recognize a difference between the virus and the host. • Cellular immune responses to hepatocyte-membrane HBV proteins do not occur. • Risk of developing chronic HBV infection is 90% in infants born to HBeAg positive mothers. In children under 5, risk is 25-30%. • Adults: • Tend to have a more vigorous immune response. • Less than 5% of those infected develop continual viremia and persistent infection.

  6. Serologic Diagnosis

  7. http://www.haps.nsw.gov.au/userData/img//hepB1.jpg

  8. Chronic Hepatitis B Infection • Early Replicative Phase: Immune Tolerance • Perinatally acquired infection • High levels of HBV DNA, HBeAg present • No liver disease—normal ALT, asymptomatic, Stage 0-1 fibrosis • Lasts 10-30 years • Replicative Phase: Immune Clearance • Spontaneous clearance of HBeAg • Often characterized by periods of increased HBV DNA and increased ALT due to immune-mediated lysis of infected hepatocytes, i.e. flares • Nonreplication Phase: Inactive Carrier State • HBeAg negative, anti-Hep B e positive, HBV DNA undetectable • ALT levels normalize, however some patients may have active inflammation

  9. Chronic Hepatitis B Infection • HBeAg-negative Chronic Hepatitis • Precore/Core Promoter Mutations • Moderate levels HBV DNA • Active liver disease and elevated ALT • Older patients • Resolution • Hallmark is the clearance of HbSAg • Does not preclude development of cirrhosis, HCC or failure. • Patients may still produce HBV DNA, which has implications in the immunosuppressed

  10. Sequelae of Chronic HBV Infection • Cirrhosis • Hepatocellular Carcinoma • Hepatic Decompensation • Extrahepatic Manifestations • Death • Prognosis is worse in endemic areas: • Prolonged replicative phase • Clearance of HBeAg causes a 2 fold decrease in death rate. • Patients who reactivate have worse prognosis. http://pathmicro.med.sc.edu/lecture/images/hepato-b.jpg

  11. Extrahepatic Manifestations • Occur in 10-20% of patients with Chronic Hep B. • Serum Sickness • Polyarteritis Nodosa • Membranous and Membranoproliferative Glomerulonephritis

  12. Genotypes • Genotype B associated with HBeAg seroconversion at an earlier age, more sustained remission, less active hepatic necroinflammation, a slower rate of progression to cirrhosis and lower rate of HCC development when compared with Genotype C. • Genotypes A and B are associated with higher rates of seroconversion with pegIFN-alpha than C and D.

  13. Indications for Therapy Acute Hepatitis • One trial demonstrated no biochemical or clinical benefit in patients treated with Lamivudine vs. placebo in 12 months. • General Rule: • Coagulopathy INR>1.5 • Persistent symptoms or marked jaundice (bilirubin >10 mg/dl) for more than 4 weeks after presentation • Fulminant Hepatic Failure • Concomitant infection with Hep C or D

  14. Indications for Therapy HBeAg-positive patients: • HBeAg-positive patients with persistently normal ALT should be tested for ALT at 3-6 month intervals • HBeAg status should be checked every 6-12 months. • HBeAg positive with HBV DNA levels >20,000 IU/mL after a 3-6 month and ALT 1-2 x ULN OR are >40 years liver biopsy w/ treatment if biopsy shows moderate/severe inflammation or significant fibrosis. • Patients who remain HBeAg positive with HBV DNAlevels>20,000 IU/mL after a 3-6month period of elevated ALT levels >2 ULN should be considered for treatment. HBeAg-negative patients: • HBeAg-negative patients with normal ALT and HBV DNA <2,000 IU/mL: Tested ALT q 3months during the first year to verify true “inactive carrier state” and then every 6-12 months. http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Chronic_Hep_B_Update_2009%208_24_2009.pdf

  15. http://knol.google.com/k/-/-/1w026jckgcwg2/18ad7q/slide4%20(1).jpghttp://knol.google.com/k/-/-/1w026jckgcwg2/18ad7q/slide4%20(1).jpg

  16. References: • Dienstag JL. Hepatitis B Virus Infection. N Eng J Med 2008;359: 1486-500. • Ganem D, Prince AM. Hepatitis B Virus Infection—Natural History and Clinical Consequences. N Eng J Med 2004; 350: 1118-29. • Liaw YF, Chu CM. Hepatitis B Virus Infection. Lancet 2009;373:582-592. • Lok ASF, McMahon BJ. Chronic Hepatitis B: Update 2009. Hepatology 2009; 3: 1-36. • Lok ASF. Clinical manifestations and natural history of hepatitis B virus infection. UpToDate

  17. Inspiration

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