Research on HBV in SCDC

1. Research on HBV in SCDC Xi Zhang, Ye Lu Shanghai Municipal Center for Disease Control and Prevention May, 2008

2. Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC

3. Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC

5. Ratio of HBsAg carrier ---7.18% • Population of HBsAg carrier --- 93 million (by the year of 2006)

6. HAV HBV HCV HEV Untyped NANB 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year Percentage of different types of virus in virus hepatitis in China from 1990-2004

7. Percentage of different types of virus in virus hepatitis in Shanghai in 2007

8. Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC

9. 1. Electron Microscope Photo of HBV Dane Particle Globular Particle Tubal Particle

10. 2. Dane Particle • Complete particle, infective HBV • Spherical, double capsid outer capsid HBsAg inner capsid HBcAg, HBeAg internal DNA ---circular, double stranded DNA polymerase

11. Gene production (protein) Gene pre-S1 pre-S1 pre-S2 pre-S2 S HBsAg pre-C HBeAg C HBcAg P DNAP X HBxAg 3. Genome of HBV pre-s2 S pre-s1 编码 P HBV DNA 3.2 kb C pre-c X

12. 4. Clinical Significance of HBV Related Antigen and Antibody • HBsAg Time of Appearance --- 2 to 6 months after HBV infection Time of Lasting --- less than 6 months for acute infection or life time for chronic infection

13. HBsAg HBV Hepatic Cell DNA Integrate S Gene Persisted Express Produce of HBsAg adr North of Yangzhi River Subtype of HBsAg adw South of Yangzhi River ayr West area of China ayw

14. Anti-HBs Time of Appearance --- late stage of acute infection or after clearance of HBsAg The appearance of anti-HBs implies the recovery from HBV infection.

15. HBcAg HBcAg is expressed ---in the HBV infected hepatitis cells or on inner capsid of Dane particle HBcAg cannot be detected in serum.

16. Anti-HBc Time of Lasting --- 6 -18 months Type of antibody ---IgM: indicate the recent infection or activity of chronic infection IgG: indicate previous infection

17. HBeAg: the degradation product of HBcAg HBV C gene C Pre C Gene Expression preC / C protein split、process HBcAg HBeAg Secreted outside cell HBeAg can be detected in serum, implies strong virus replicate and infectivity.

18. Anti-HBe Time of Appearance --- after clearance of HBeAg The appearance of anti-HBs implies the reduction of virus replicate and infectivity.

19. Clinical Implication of Antigen & Antibody of HBV

20. Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC

21. Progression from HBV infection to cancer Exposure to HBV ?% ?% No infection Infection 90% 10% Acute infection (HBV clearance) Chronic infection ~25% Asymptomatic carriers Cirrhosis Slowly Progressive HCC Death Years

22. Transmission of HBV Infection Maternal-neonatal Iatrogenic Sexual

24. The younger the infection age , The worse the prognosis • Infected at birth, almost all will develop into chronic hepatitis • Infected at 1-2 year old, 80% will develop into chronic hepatitis • Infected at 3-6year old, 50% will develop into chronic hepatitis • Infected at adult, only 2-6% will develop into chronic hepatitis

25. HBV Vaccine Immunization in China Immunized object • New born • Juvenile • High risk population

26. HBV Vaccine Immunization in China Immunized object • New born • Juvenile • High risk population

27. 2002.01.01 2005.06.01 1992.01.01 Immunization of new born was administered under immunization program. Immunization of new born was free, with only ￥10 fee. Immunization of new born was totally free.

28. 12 11.3 10.2 9.7 10 2002 8 1992 Percentage of HBsAg Carrier (%) 7.1 6 4.8 4 3.1 2 0 1~ 5~ 10~ 15~ 20~ 30~ 40~ 50~ 60~ Effect of HBV Immunization in China In 2006, the data are 0.96% and 2.42% Age

30. Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Distribution and Immunization of HBV • Research on HBV Related Fibrosis in SCDC

31. (Disease process) Healthy CLD HCC Exposure to HBV Chronic infection Chronic inflammation Metastasis Fibrosis Cirrhosis HCC • Liver fibrosis is the middle stage in the course of chronic hepatitis B virus infection. • Liver fibrosis is reversible. • Liver fibrosis will develop into cirrhosis and eventually HCC if not treated at early stage.

32. Reversible of liver fibrosis Ramón Bataller and David A. Brenner, J. Clin. Invest,2005, 115:209–218

33. DIGE SELDI Research on early diagnosis of HBV related liver fibrosis Clinical feature of subjects Table 1 Table 2

34. DIGE Result 12 up-regulated 18 down-regulated Data analysis in process SELDI Result 7 up-regulated 13 down-regulated Peptide identification in process

35. Conclusion • HBV infection is the most important pathogen of virus hepatitis in China. • Antigen and antibody against HBV infection are useful in clinical diagnosis. • Immunization of HBV vaccine can prevent HBV infection in children. • Research on HBV related disease is highly interested in China.

36. Acknowledgement • Laboratory of Microbiology, SCDC • Department of Molecular Biology for Public Health, SCDC • Department of Immunization, SCDC • Department of Acute Infectious Disease Prevention, SCDC • China CDC

37. Thank you for your attention !