Research on HBV in SCDC

Xi Zhang, Ye LuShanghai 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)

Percentage of different types of virus in virus

hepatitis in China from 1990-2004

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Year

HAV HBV HCV HEV Untyped NANB

Percentage of different types of virus in virus

hepatitis in Shanghai in 2007

9%

49%

7%

12%

23%

HAVHBVHCVHEVUntyped

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

internalDNA ---circular, double strandedDNA polymerase

3. Genome of HBV

pre-s1

pre-s2S

P

C

pre-cX

HBV DNA 3.2 kb

编码

pre-S1 pre-S1

pre-S2 pre-S2

S HBsAg

pre-C HBeAg

C HBcAg

P DNAP

X HBxAg

Gene Gene production(protein)

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

Persisted

Express

HBsAgHBV

S Gene

IntegrateHepatic Cell

DNA

Subtype of HBsAg adr

adw

ayr

ayw

North of Yangzhi River

North of Yangzhi River

South of Yangzhi River

South of Yangzhi River

West area of China West area of China

Produce of HBsAg

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 is expressed ---in the HBV infected hepatitis cells

or on inner capsid of Dane particle

HBcAg

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 genePre C C

preC / C protein

HBeAg HBcAg

Gene Expression

split 、 process

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 red

uction of virus replicate and infectivity.

IgM IgG

－ － － － － ＋Previously infected with HBV or vaccinated byHBV bacterin, has immunity against HBV

＋ － － － －／＋ －HBV carrier with normal liver function or HBVpatients with abnormal liver function

＋ － － ＋ ＋ － Convalescent HBV patient with infectivity

＋ ＋／－ － ＋ ＋ － Convalescent HBV patient with infectivity

＋ ＋ ＋／－ － － － HBV patient with strong infectivity

－ － － ＋／－ ＋ ＋ Convalescent HBV patient without infectivity

Anti HBs Clinical Implication Anti HBc

HBsAg HBeAg Anti HBe

Clinical Implication of Antigen & Antibody of HBV

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

Exposureto HBV

No infection

Chronic infection

CirrhosisAsymptomaticcarriers

SlowlyProgressive

HCC

?% ?%

10%

Years

Infection

Acute infection(HBV clearance)

90%

Death

~25%

Iatrogenic

Sexual

Maternal-neonatal

Transmission of HBV Infection

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

1992.01.01 2002.01.01 2005.06.01

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.

1~ 5~ 10~ 15~ 20~ 30~ 40~ 50~ 60~0

2

4

6

8

10

12

Per

cen

tag

e o

f H

BsA

g C

arri

er (

%)

2002

1992

3.1

4.8

7.1

9.710.2

11.3

Effect of HBV Immunization in China

In 2006, the data are 0.96% and 2.42%

Age

0-4 year 5-9 year 10-14 year 15-19 year whole

1990 2. 11 1. 27 2. 72 6. 20 10. 531991 1. 61 1. 38 2. 41 8. 53 9. 371992 1. 36 0. 57 2. 85 7. 64 9. 121993 0. 65 0. 83 2. 02 6. 14 6. 621994 0. 32 0. 71 1. 29 3. 99 5. 581995 0. 32 0. 24 1. 29 3. 55 5. 011996 0. 00 0. 24 0. 35 2. 95 4. 961997 0. 00 0. 14 0. 55 3. 53 4. 891998 0. 59 0. 28 0. 33 3. 79 5. 141999 0. 29 0. 00 0. 22 3. 52 5. 652000 0. 88 0. 56 0. 54 7. 81 18. 202001 0. 64 0. 42 0. 59 5. 37 14. 362002 0. 95 0. 41 0. 94 5. 24 18. 642003 0. 94 0. 21 0. 47 5. 01 16. 872004 0. 65 0. 86 0. 97 6. 08 16. 01

Incidence of HBV（/100,000）

Incidence of HBV in Shanghai

Year

Content

• Situation of Chronic HBV Infection

• Immunology of HBV Infection

• Distribution and Immunization of HBV

• Research on HBV Related Fibrosis in SCDC

Healthy CLD HCC (Disease process)

Exposureto HBV

MetastasisChronic

inflammationChronic

infection Cirrhosis HCCFibrosis

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

Research on early diagnosis of HBV related liver fibrosis

Milder Significantfibrosis fibrosis

Number 7 5 10 7Mean±SD 35.7±4.1 40.5±10.5 35.1±9.8 37.6±14.5

Gender(Male/Female) 7/0 5/0 10/0 7/0

Screening study

Healthy Cirrhosis

DIGE

SELDI

Milder Significantfibrosis fibrosis

Number 48 32 48 23Mean±SD 33.0±9.0 36.4±10.3 35.4±12.5 38.8±13.1

Gender(Male/Female) 43/5 25/7 37/11 17/6

Validation study

Healthy Cirrhosis

Clinical feature of subjects

Table 1

Table 2

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

2527

2930

2628

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

7 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

7 8

12

12 3 45 6

9 10

11

7 8

12

12 3 45 6

9 10

7 8

12

12 3 45 6

7 8

12

12 3 47 8

12

7 87 8

12

12 3 45 6

9 10

11

13 1415

16 17 18 19

20 21 22 23

24

2527

2930

2628

DIGE Result

12 up-regulated

18 down-regulated

SELDI Result

7 up-regulated

13 down-regulated

Peptide identification in process

Data analysis 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

Thank you for your attention !