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Hepatitis B The Basics

Hepatitis B The Basics. David Wong University of Toronto March 2005. Objectives. Learn about the various tests used to assess hepatitis B infection Understand the natural history of hepatitis B Use what you learned to manage patients with hepatitis B. What we know about HBV.

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Hepatitis B The Basics

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  1. Hepatitis BThe Basics David Wong University of Toronto March 2005

  2. Objectives • Learn about the various tests used to assess hepatitis B infection • Understand the natural history of hepatitis B • Use what you learned to manage patients with hepatitis B

  3. What we know about HBV • Viral infection that can cause chronic hepatitis, cirrhosis, cancer • Ranks as top 10 infectious killer in the world • HBV can live in host for decades • Virus can adapt through mutations • Immune system can adapt to virus • Vaccine can prevent infection • Cure of chronic infection unlikely

  4. Global HBsAg Prevalence ³8% - High: Early childhood infection, lifetime risk of infection 60% 2-7% - Intermediate: Infection at all ages, lifetime risk of infection 20%-60% <2% - Low: Infection as adult, lifetime risk of infection <20%

  5. HBV in body fluids Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk

  6. Transmission risk factorsUSA 1992-1993 Heterosexual* (41%) Injecting Drug Use (15%) Homosexual Activity (9%) Household Contact (2%) Health Care Employment (1%) Unknown (31%) Other (1%) * Includes sexual contact with acute cases, carriers, and multiple partners. Source: CDC Sentinel Counties Study of Viral Hepatitis

  7. Outcome of HBV infection by age 100 80 60 Chronic Infection 40 20 Symptomatic Infection 0 1-6 months 7-12 months Older Children Birth 1-4 years Age at Infection

  8. Immunity after Twinrix Data from Glaxo Smithkline

  9. Objectives • Learn about the various tests used to assess hepatitis B infection • Understand the natural history of hepatitis B • Use what you learned to manage patients with hepatitis B

  10. SerologyAntigens and Antibodies Antibodies Test for antibody Antibodies can bind to specific antigen Test for antigen Circulating protein

  11. Nucleic Acid TestingHybridization vs Amplification Hybridization: Visualization of unamplified probe Amplification (PCR) Visualization of amplified product

  12. Assays of HBV viral load 1010 108 Copies/ml 106 104 1 pg/mL ~ 283,000 copies/mL 5 pg/mL ~ 1.4E6 copies/mL 1 IU ~ 5.6 copies/mL  102 Qual Quant PCR bDNA Liquid Hybrid capture PCR hybridization Pawlotsky JM. Gastroenterology 2002;122:1554-68

  13. Interpreting viral loads Old Scheme DW Scheme High High Low Moderate Low Negative Negative

  14. HBV Life Cycle

  15. HBsAg – Envelope antigenGood test indicating infection

  16. HBeAg – nucleocapsid protein Old test for viral load

  17. SummaryTests for hepatitis B • Infection • HBsAg: ongoing infection • Anti-HBs: infection resolved • Viral load or infectivity • Indirect tests • HBeAg: high viral load • Anti-HBe: low viral load • Direct tests • Nucleic acid testing

  18. Objectives • Learn about the various tests used to assess hepatitis B infection • Understand the natural history of hepatitis B • Use what you learned to manage patients with hepatitis B

  19. Immune responses to HBV

  20. Natural History of HBV

  21. Immune Tolerance • No immune attack on virus • Viral load very high • HBV DNA > 1010 copies/mL • HBeAg-positive • ALT levels normal • Liver biopsy • No inflammation • No fibrosis • Lots of HBV in liver • Treatment - NO HBeAg HBV DNA ALT

  22. Immune Clearance • Immune attack on virus • Viral load getting lower • HBV DNA 10(4)5-10 copies/mL • HBeAg-positive to negative • ALT levels high • Liver biopsy • Inflammation • Fibrosis increasing • Moderate levels HBV in liver • Treatment - YES HBeAg HBV DNA ALT

  23. Inactive carrier • Immune control • Viral load low • HBV DNA <10(4)5 copies/mL • HBeAg negative • ALT levels normal • Liver biopsy • No Inflammation • Fibrosis established • Low levels HBV in liver • Treatment - NO HBeAg HBV DNA ALT

  24. Reactivation • Loss of immune control • Viral load fluctuating or high • HBV DNA <10(4)5 to >10(4)5-10 • HBeAg negative • ALT levels fluctuate • Liver biopsy • Inflammation • Fibrosis increasing • Fluctuating levels HBV in liver • Treatment - YES HBeAg HBV DNA ALT

  25. Review: History of HBV

  26. Acute infection with recovery Symptoms anti-HBe HBeAg Total anti-HBc Titer anti-HBs IgM anti-HBc HBsAg 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure

  27. HBV evolving to chronicity Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titer IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

  28. Objectives • Learn about the various tests used to assess hepatitis B infection • Understand the natural history of hepatitis B • Use what you learned to manage patients with hepatitis B

  29. True, *False or Don’t know? • Patient A has been told he probably needs treatment of his HBV • ALT 125, HBeAg-positive • HBV DNA 5 x 107 copies/mL • Patient A is reluctant to start therapy and wants another test done in 2-3 months • ALT 85 • HBV DNA tripled 1.5 x 108 copies/mL • This patient must start therapy right away as his hepatitis B has gotten worse

  30. Patient A – Answer: FALSE • Active disease • ALT 125, HBeAg-positive • HBV DNA 5 x 107 copies/mL • Increase viral load to 1.5 x 108 copies/mL • 7.70 log copies to 8.18 log copies • Increase viral load by 0.48 log copies • STABLE VIRAL LOAD • Treatment? • Yes or wait

  31. Patient B • 45 year old man • ALT 25, HBeAg-POS, HBV DNA 5.8x1010 copies/mL (10.8 log copies) • This patient’s status is: • *A. Immune Tolerant – treat • B. Immune Tolerant – don’t treat • C. Inactive Carrier – treat • D. Inactive Carrier – don’t treat

  32. Patient C • 45 year old man, hepatitis B for a long time, not being followed, asymptomatic • ALT 22, HBeAg-negative, HBV DNA 8.2 x 104 copies/mL (4.91 log copies) • Patient management is: • A. Inactive carrier, follow-up family physician • *B. Status unknown • C. Immune Tolerance: yearly follow-up

  33. Risk of ALT flare HBV Viral Load 2x105 cp/mL VL<2E5 P<.0001 VL>2E5

  34. True or *False? • Patient D with HBeAg-negative CHB • 0-48 wks: Rx PegIFN treatment • 72 wks: HBV DNA is negative (<400 copies/mL) • This is an SVR and his hepatitis B is either cured or will remain inactive

  35. Reactivation • Loss of immune control • Viral load fluctuating or high • HBV DNA <10(4)5 to >10(4)5-10 • HBeAg negative • ALT levels fluctuate • Liver biopsy • Inflammation • Fibrosis increasing • Fluctuating levels HBV in liver • Treatment - YES HBeAg HBV DNA ALT

  36. True, *False or Don’t know? • Patient A with HBeAg-positive CHB • 0-48 wks: Rx PegIFN treatment • 72 wks: HBV DNA is negative (<400 copies/mL) • Also HBeAganti-HBe, HBsAganti-HBs • This is a cure of hepatitis B infection

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