1. Understanding Hepatitis-B Prof Arif M. Siddiqui MBBS(KE);MRCP(UK);FRCP(London) FRCP(Edin);FRCP(Glasg) AllamaIqbal Medical College/Jinnah Hospital Lahore

2. Prologue There has been an explosion of information on Hepatits B in the last few years and this many doctors have not been able to grasp fully. New management guidelines have emerged. I will, in this short time, try to explain few basic important facts on which the understanding and management of this disease is based.

3. PAKISTAN 151 millionpopulation 35% Urban 65% Rural 22 millionchildren under 5 years 6.6 million childreninfected by HBV before the age of 5 years go on to develop Chronic Hepatitis B infection. Hepatitis 2.6% prevalence among general public 3.8% prevalence among pregnant women Ref: WHO/MDG

4. HBV worldwide distribution, 2000sWHO2003 WHO 2003

5. HBV by age at infection

6. Global distribution of HBV genotypes (A to H) A, D B,C G A, C, B, D, G B, C A,D F, H E F A * Defined by divergence in the entire genome sequence > 8%.

7. Hepatitis B Source: Centers for Disease Control and Prevention, USA Revised December 2003

9. Anti-HBe

11. Albumin

13. HBeAg

15. AST

16. BilirubinHBV

17. Hepatitis-B HBsAg Anti-HBsAg HBe Anti-HBe HBc (does not appear in blood) Anti-HBc IgG & IgM HBV-DNA by PCR

18. Hepatitis-B HBsAg Anti-HBsAg HBe-Ag Anti-Hbe (Hbe-Ab) HBc (does not appear in blood) Anti-HBcIgG & IgM HBV-DNA by PCR

19. Hepatitis-B HBsAg Anti-HBsAg Hbe-Ag Anti-HBe HBc (does not appear in blood) Anti-HBcIgG & IgM HBV-DNA by PCR

20. Hepatitis-B HBsAg Anti-HBsAg HBe-Ag Anti-HBe HBc (does not appear in blood) Anti-HBcIgG & IgM HBV-DNA by PCR

21. Hepatitis-B HBsAg Anti-HBsAg HBe Anti-HBe HBc (does not appear in blood) Anti-HBc IgG & IgM HBV-DNA by PCR

22. Hepatitis-B HBsAg Anti-HBsAg Hbe Anti-Hbe HBc (does not appear in blood) Anti-HBc IgG & IgM HBV-DNA by PCR

23. Hepatitis-B HBsAg Anti-HBsAg Hbe Anti-Hbe HBc (does not appear in blood) Anti-HBc IgG & IgM HBV-DNA by PCR

24. Hepatitis-B HBsAg Anti-HBsAg Hbe Anti-Hbe HBc (does not appear in blood) Anti-HBc IgG & IgM HBV-DNA by PCR

25. Acute HBV Infection: Appearanceand Disappearance of Viral Markers viraemia (HBV-DNA, DNA-polymerase) ALT HBeAg HBsAg anti-HBc anti-HBs ALT anti-HBe 8 10 12 2 4 6 2 4 6 Months Years HBV

26. Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course 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. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (years) HBeAg anti-HBe HBsAg Total anti-HBc Titer IgM anti-HBc 0 4 8 16 20 24 28 36 12 32 52 Years Weeks after exposure

28. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (years) HBeAg anti-HBe HBsAg Total anti-HBc Titer IgM anti-HBc 0 4 8 16 20 24 28 36 12 32 52 Years Weeks after exposure

29. Natural Course of CHB Immune Tolerance Immune Clearance Phase Late/Residual Pre-C mutant Reactivation HBV-DNA anti-HBe(+) HBeAg(+) HBsAg Clearance Cirrhosis HCC ALT/Grading HBeAg Nuclear Cytoplasm (++ ~) (-) (+++) Membrane (++ ~) HBsAg/preS Membrane Cytoplasm (++ ~) Cytoplasm (+++) (+++) Membrane (++ ~) HLA-1 (-) (++) (++) 20 40 60 Age

30. Treatment When to treat With what to treat How to monitor How long to treat