1. Hepatitis viruses

2. 5 hepatitis viruses:
Hepatitis A virus(HAV)
Hepatitis B virus(HBV)
Hepatitis C virus(HCV)
Hepatitis D virus(HDV)
Hepatitis E virus(HEV)

3. Characteristic properties of hepatitis
item
HAV
HBV
HCV
HDV
HEV
Classification
Picorna-
viridae
Hepadnaviridae
Flavi-v
iridae
Defective virus
Caliciviridae
Diameter(nm) 27 42
36-62 36 32
Nucleic acid
+ssRNA
dsDNA
-ssRNA
Transmission
Fecal-oral
Blood
transfusion,
Vertical
Blood transfusion,
Chronic hepatitis — +
Hepatoma
Vaccine

4. sectionⅠ Hepatitis A virus ( HAV )
ⅠBiological properties
1.spherical, 27nm, icosahedral, non-enveloped, VP1-VP4.
2.One serotype.
3.+ssRNA, 7500bp.

5. ⅠBiological properties
4.Chimpanzee and marmoset are susceptible.
5.Culture: difficult, no CPE, grow slowly.IFA.
6.Resistance: strong, resistant to acid;liposoluble agents, dry, inactivated at 100℃ 5min.

6. Hepatitis A virus particles found in fecal extracts by immunoelectron microscopy.

7. Ⅱ.Pathogenesis and immunity
1.Source of infection: patients, subclinical infected person.
2.Transmission: fecal-oral route.
3.Pathogenic mechanism: HAV----mouth----intestine----blood----liver
Mechanism of hepatocyte damage:
viral direct effect
immune injure
4.Immunity: anti-HAV IgG are protective, can neutralize viral infectivity.

9. Clinical findings: Incubation period:10-50days(30days)
acute hepatitis A, rarely chronic
Some infected people are asymptomatic
Rarely fatal

10. Ⅲ.Microbiological detection
1.Detect HAV virion, antigen or RNA in feces: IEM, ELISA or RT-PCR.
2.Detect anti-HAV IgM in serum: ELISA.
Ⅳ.Control
1.γ-globulin for urgent prevention.
2.Vaccine: attenuated or inactivated vaccines are commonly used.
Ⅴ.treatment
No special treatment is need because Hepatitis A is self-limiting disease. Supportive care.

11. SectionⅡ Hepatitis B virus ( HBV )
belong to Hepadnaviridae
Ⅰ.Biological properties
1.structure:
Partly dsDNA, circular, 3200bp, the long strand(negative strand) is complete, there is a gap in the short strand(positive strand).
2 layer capsids:
the inner capsid: icosahedral, carry HBcAg, HBeAg
the outer capsid: carry HBsAg, pre-S1 Ag, pre-S2 Ag.

12. 2. 3 different particles can be seen in the blood in HBV infection
1)Dane particle: intact, mature, and infectious virion, 42nm.
2)Small spherical particle: 22nm, carry HBsAg.
3)Tubular particle: 22nm in diameter, nm in length, mainly consists of HBsAg.

16. 大球形颗粒模式图

17. 3.Gene and encoded proteins
4.ORF: S, C, P, X regions, located in the long strand.
S region: HBsAg, pre-S1 protein, pre-S2 protein.
C region: HBcAg, HBeAg.
P region: DNA polymerase.
X region: X protein.

19. 4.Replication
There are some parallels between the hepadnaviruses and the retroviruses, in that:
1)Both synthesize DNA from an RNA template
2)There is base sequence homology between the enzymes involved.

21. 5.Ags & Abs
1)HBsAg: 4 subtypes: adr, adw, ayr, ayw;
HBsAg ( + ): indicates that the patient is infected with HBV, either as a recent acute infection or as a carrier;
anti-HBs: protective.

22. 2) HBcAg: not easily detective in serum
anti-HBc: not protective
anti-HBc ( + ): viral multiplication, active infection.
3) HBeAg: is correlated strongly with the detection of viral DNA, virions and viral DNA polymerase in the serum; variable.
HBeAg ( + ): viral multiplication, active infection.
anti-HBe: protective

23. 4)pre-S1 Ag, pre-S2 Ag: be related to the adsorption of virus;
enhance the antigenicity of S protein.
6.Can not grow in any cell culture.
7.Chimpanzee is susceptible to HBV.
8.Resistance:low temperature, dry, UV, alcohol, stable 60℃1h, 100℃10min.
Sensitive to autoclaving, sodium hypochlorite

24. Ⅱ.Pathogenesis & immunity
1.Source of infection: patients, HBsAg-carrier.
2.Transmission way:
① By blood or blood products;
② Sexual transmission;
③ Vertical transmission: from mother to child.
④ close contact
3.Mechanism of pathogenesis: hepersensitivity reactions ( type Ⅱ, Ⅲ,Ⅳ ).

25. Clinical Findings
Clinical types: acute, chronic, severe hepatitis, hepatocirrhosis, chronic carrier
Carcinogenesis: hepatocellular carcinoma

26. Carcinogenesis The evidence
Hepatoma incidence in hepatitis B patients is higher than that in non- hepatitis B patients.
The possibility of detection of HBV infection in hepatoma patients is higher than that of normal people.
Integrated HBV DNA (X region) can be found in hepatocyte nucleus of hepatoma.
Animal hepatitis viruses can induce hepatoma in animals, and integrated viral DNA can also be found in hepatocyte nucleus.

27. Ⅲ.Microbiological detection
Detecte Ags & Abs: HBsAg, anti-HBs, anti-HBc, HBeAg, anti-Hbe.

28. Applications of antigen-antibody detection
Screen blood donor
Help diagnose hepatitis B
Help judge the prognosis and outcome
Investigate epidemiology of hepatitis B and detect chronic carriers or asymptomatic carriers.
Judge people’s immunity level and effect of vaccination.

29. Interpretation of antigen and antibody
HBsAg
the presence of HBV infection
anti-HBs
previous HBV vaccination or previous infection which has recovered
the individual obtains protection against re-infection.

30. Interpretation of antigen and antibody
HBeAg
the multiplication of HBV virion
the patient serum is highly infectious
Persistent high titer indicates chronic conversion
anti-HBe
patient is recovering and get some immunity to HBV

31. Interpretation of antigen and antibody
anti-HBc IgM
acute hepatitis B or a recent HBV infection in which replication of virion presents
anti-HBc IgG
previous HBV infection or chronic HBV infection

32. Prevention and Treatment
Cutting transmission way
Treatment
Supportive care: major

33. CONTROL Passive immunization Active immunization
Hyperimmune hepatitis B immunoglobulin
HBIG
Active immunization
Vaccine
HBsAg

34. Hepatitis B can be prevented!
If you have never had hepatitis B, you can get 3 shots . . . 3 2 1
. . . and get long lasting protection.

35. if the mother has Hepatitis B
Baby Shots
for Hepatitis B
if the mother has Hepatitis B
Birth
1 - 2 months old +
Hepatitis B
Vaccine
Hepatitis B
Vaccine
H-BIG
6 months old
Hepatitis B
Vaccine

36. Geographic Distribution of Chronic HBV Infection
HBsAg Prevalence
³8% - High
2-7% - Intermediate
<2% - Low 36

37. sectionⅢ Hepatitis C virus ( HCV )
Ⅰ.Biological properties
1 +ssRNA, 9.4kb.
2 50nm.
3 lipo-enveloped.
4 Human and chimpanzee are susceptible to HCV.
5 Can not culture.
6 easy variation.

38. Ⅱ.Pathogenesis
1 Transmission: transmitted mainly by blood and blood products.
2 The disease is usually mild. Chronic infection occurs in 80% of cases.
3 HCV is closely related to cirrhosis, hepatoma.

39. Ⅲ.Microbiological detection
1 Detect anti-HCV: ELISA.
2 Detect viral RNA: RT-PCR.
Ⅳ.Control
Neither active nor passive immunization is available.

40. sectionⅣ Hepatitis D virus ( HDV )
Spherical, 35-37nm.
–ssRNA, circle, 1700bp.
Outer capsid is HBsAg.
One serotype.
Defective virus.
Human and chimpanzee are susceptible to HDV.

41. Transmission: same as HBV.
Infecious mode: Coinfection
and Superinfection
Detect HDAg & anti-HDV.

42. sectionⅤ Hepatitis E virus ( HEV )
Ⅰ.Biological properties
1 Spherical, 27-38nm.
2 +ssRNA, 7.2kb.
3 Not grow in cell culture.

43. Ⅱ.Pathogenesis
1 Transmission: fecal-oral route.
2 Mainly involve young and adults.
3 Incubation period: average 40 days.
4 Cause acute hepatitis, 4-6 weeks recovery, no chronic.
5 Mortality 1-2%, pregnant woman 10-20%.
Ⅲ.Microbiological detection
1 Detect viral Ag in faeces: IEM.
2 Detect anti-HEV IgM in serum: ELISA.