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Research on HBV in SCDC. Xi Zhang, Ye Lu Shanghai Municipal Center for Disease Control and Prevention May, 2008. Content. Situation of Chronic HBV Infection Immunology of HBV Infection Immunization of HBV Research on HBV Related Fibrosis in SCDC. Content.
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Research on HBV in SCDC Xi Zhang, Ye Lu Shanghai Municipal Center for Disease Control and Prevention May, 2008
Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC
Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC
Ratio of HBsAg carrier ---7.18% • Population of HBsAg carrier --- 93 million (by the year of 2006)
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
Percentage of different types of virus in virus hepatitis in Shanghai in 2007
Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC
1. Electron Microscope Photo of HBV Dane Particle Globular Particle Tubal Particle
2. Dane Particle • Complete particle, infective HBV • Spherical, double capsid outer capsid HBsAg inner capsid HBcAg, HBeAg internal DNA ---circular, double stranded DNA polymerase
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
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
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
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.
HBcAg HBcAg is expressed ---in the HBV infected hepatitis cells or on inner capsid of Dane particle HBcAg cannot be detected in serum.
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
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.
Anti-HBe Time of Appearance --- after clearance of HBeAg The appearance of anti-HBs implies the reduction of virus replicate and infectivity.
Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Immunization of HBV • Research on HBV Related Fibrosis in SCDC
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
Transmission of HBV Infection Maternal-neonatal Iatrogenic Sexual
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
HBV Vaccine Immunization in China Immunized object • New born • Juvenile • High risk population
HBV Vaccine Immunization in China Immunized object • New born • Juvenile • High risk population
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.
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
Content • Situation of Chronic HBV Infection • Immunology of HBV Infection • Distribution and Immunization of HBV • Research on HBV Related Fibrosis in SCDC
(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.
Reversible of liver fibrosis Ramón Bataller and David A. Brenner, J. Clin. Invest,2005, 115:209–218
DIGE SELDI Research on early diagnosis of HBV related liver fibrosis Clinical feature of subjects Table 1 Table 2
DIGE Result 12 up-regulated 18 down-regulated Data analysis in process SELDI Result 7 up-regulated 13 down-regulated Peptide identification in process
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.
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