1 / 36

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.

evea
Download Presentation

Hepatitis B The Basics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related