3. Etiology
Hepatitis B virus (HBV)
HBV is a kind of hepadnavirus
Three particles in serum:
spherical particles and tubular particles with a
diameter of 20 nm, composed of HBsAg
large particles with a diameter of 42 nm, named Dane
particle. It consists of an outer protein shell (envelope,
contain HBsAg) and an inner body ( core, contain
HBcAg, HBeAg, HBV-DNA and DNAP )
5. pathology
Three antigen-antibody system
HBsAg-- anti-HBs system:
HBsAg appears 1-2 weeks (late up to 11-12 weeks)
after exposure, persists for 1-6 weeks( even 5 months)
in acute hepatitis B.
In chronic patients or carrier, HBsAg persist many
years
HBsAg is the marker of infectivity
HBsAg can be found in blood and secretions: saliva,
urine, semen, tears, sweat and breast milk
Anti-HBs appear after HBsAg disappear several weeks
(or months) anti-HBs is protective antibody, can persist
for many years
6. pathology
HBcAg—anti-HBc system
HBcAg can be found in the nuclei of liver cells, no free
HBcAg in serum
HBcAg is the marker of replication of HBV
The stage called window phase
Anti-HBc IgM is a marker of acute infection and acute
attack of chronic infection of HBV. Anti-HBc IgG is the
marker of past infection, high titer means low level
replication of HBV
7. pathology
HBeAg—anti-HBe system
HBeAg is a soluable antigen
HBeAg is a reliable indicator of active replication of
HBV
Anti-HBe is a marker of reduced infectivity. If exist
long may be a marker of integration of HBV into liver
cell
8. Pathogenesis
Hepatitis B:
HBV invades into the human body by skin and
mucosa, Via blood flow enters the liver and other
organs such as pancreas, bile ducts, vessels, WBC,
bone marrow, glomerular basement membrane
HBcAg,HBsAg,HBeAg and HLA-Ⅰ appear on the
liver cells infected with are recognized by CTL
simultaneously and lead to the cytolysis of liver cells
9. Pathogenesis
Helper T cell are activated by the receptor of HLAon its surface combing with HBsAg, HBcAg and
HLA- antigen on the B cells promote B cell to
release anti-HBs and clear HBV
The representation of HBcAg on the liver cells may
cause cytopathy
10. Hepatitis B - Clinical Features
Incubation period:
Clinical illness (jaundice):
Acute case-fatality rate:
Chronic infection:
Premature mortality from
chronic liver disease:
Average 60-90 days
Range 45-180 days
<5 yrs,
<10%
5 yrs,
30%-50%
0.5%-1%
<5 yrs,
30%-90%
5 yrs,
2%-10%
15%-25%
11. Spectrum of Chronic Hepatitis B Diseases
1.Chronic Persistent Hepatitis 2.Chronic
Active
Hepatitis
exacerbations of hepatitis
3.Cirrhosis of Liver
4.Hepatocellular Carcinoma
asymptomatic
-
symptomatic
12. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg
anti-HBe
Total anti-HBc
Titre
0
4
anti-HBs
IgM anti-HBc
HBsAg
8
12 16 20 24 28 32 36
Weeks after Exposure
52
100
13. Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titre
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
Weeks after
52
Years
14. Outcome of Hepatitis B Virus Infection
by Age at Infection
100
100
80
) %
(
c no h C no t cef nI
i r
i
60
40
Chronic Infection
60
40
Chronic Infection (%)
20
20
Symptomatic Infection
0
Birth
1-6 months
7-12 months
Age at Infection
1-4 years
0
Older Children
and Adults
Symptomatic Infection (%)
80
15. Global Patterns of Chronic HBV
Infection
High (>8%): 45% of global population
lifetime risk of infection >60%
early childhood infections common
Intermediate (2%-7%): 43% of global population
lifetime risk of infection 20%-60%
infections occur in all age groups
Low (<2%): 12% of global population
lifetime risk of infection <20%
most infections occur in adult risk groups
16.
17. Concentration of Hepatitis B
Virus in Various Body Fluids
High
Moderate
blood
serum
wound exudates
semen
vaginal fluid
saliva
Low/Not
Detectable
urine
feces
sweat
tears
breast milk
18. Hepatitis B Virus
Modes of Transmission
Sexual - sex workers and homosexuals are
particular at risk.
Parenteral - IVDA, Health Workers are at
increased risk.
Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
19. .
Diagnosis
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or immunity to HBV
infection.
anti-HBc IgM - marker of acute infection.
anti-HBcIgG - past or chronic infection.
HBeAg - indicates active replication of virus and therefore
infectiveness.
Anti-Hbe - virus no longer replicating. However, the patient can
still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate
than HBeAg especially in cases of escape mutants. Used mainly
for monitoring response to therapy.
20. Treatment
In acute hepatitis B the treatment is basically
symptomatic
Rest
Ant emetics to control vomiting
Plenty of fluids and carbohydrates
Hepatotropic agents
21. Treatment
Chronic Hepatitis B
Interferon - for HBeAg +ve carriers with chronic active
hepatitis. Response rate is 30 to 40%.
Lamivudine - a nucleoside analogue reverse
transcriptase inhibitor. Well tolerated, most patients
will respond favorably. However, tendency to relapse
on cessation of treatment. Another problem is the rapid
emergence of drug resistance.
Successful response to treatment will result in the
disappearance
of
HBsAg,
HBV-DNA,
and
seroconversion to HBeAg.
22. Prevention
Vaccination - highly effective recombinant vaccines are
now available. Vaccine can be given to those who are at
increased risk of HBV infection such as health care
workers. It is also given routinely to neonates as
universal vaccination in many countries.
Hepatitis B Immunoglobulin - HBIG may be used to
protect persons who are exposed to hepatitis B. It is
particular efficacious within 48 hours of the incident. It
may also be given to neonates who are at increased risk
of contracting hepatitis B i.e. whose mothers are
HBsAg and HBeAg positive.
Other measures - screening of blood donors, blood and
body fluid precautions.
24.
Hepatitis C virus (HCV)
HCV is a member of flavivirus family.
HCV genome is a single stranded positive-sense RNA
and contains 9.4kb
HCV genome may be divided into many types and
subtypes.
Resistance
Antigen-antibody system
The concentration of HCV in blood is low, HCV Ag has
not be detected, anti-HCV is the indicator of infection
and the marker of infectivity
HCV-RNA
HCV-RNA may be detected from blood or liver tissue,
it’s the direct evidence of infectivity
25. Hepatitis C - Clinical Features
Incubation period:
Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice):
30-40% (20-30%)
Chronic hepatitis:
70%
Persistent infection:
Immunity:
85-100%
No protective
antibody
response identified
26. Chronic Hepatitis C Infection
The spectrum of chronic hepatitis C infection is
essentially the same as chronic hepatitis B infection.
All the manifestations of chronic hepatitis B infection
may be seen, albeit with a lower frequency i.e. chronic
persistent hepatitis, chronic active hepatitis, cirrhosis,
and hepatocellular carcinoma.
27. Hepatitis C Virus Infection
Typical Serologic Course
antiHCV
Symptoms
Titr
e
ALT
Normal
0
1
2
3 4 5 6
Mont
hsTime after
Exposure
1
2 3
Years
4
28. Risk Factors Associated with
Transmission of HCV
Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-positive
contact
Multiple sex partners
Birth to HCV-infected mother
29.
30. Laboratory Diagnosis
HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at
least 4 weeks after infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR
and branched DNA. May be used to diagnose HCV
infection in the acute phase. However, its main use is in
monitoring the response to antiviral therapy.
31. Treatment
Acute infection
Chronic infection
Interferon - may be considered for patients with
chronic active hepatitis. The response rate is around
50% but 50% of responders will relapse upon
withdrawal of treatment. However addition of
Ribavirin – Improves the response rate to almost 70%.
32. Treatment
Different genotypes of HCV have been identified and
have been named as genotype 1 to 8 and there are still
many which presently are untypeable.
Many different types of interferons are also available
including conventional, pegylated, and consensus
interferon.
Genotype 2 & 3(common subtypes in Pakistan) respond
well to conventional interferon
33. Prevention of Hepatitis C
Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions
35.
Hepatitis D virus (HDV)
HDV (Delta hepatitis virus) is a kind of defective virus
HDV is found in the nuclei of infected hepatocytes and replicate
HDV genome is a circular single strand RNA and contains 1.7kb
The replication of HDV depends on HBV or other hepadnavirus,
coated by HBsAg in blood
HDV has one antigen-antibody system
No free HDAg is detected in blood, it’s in the nuclei of
hepatocytes; anti-HDV can be detected by RIA or ELISA in
serum
HBV and HDV co-infection or superinfection may make the
disease exacerbation and may lead to fulminant hepatitis
HDV RNA may be detected from liver cells, blood or humor.
37. Hepatitis D - Clinical Features
Co-infection
– severe acute disease.
– low risk of chronic infection.
Super-infection
– usually develop chronic HBV infection.
– high risk of severe chronic liver disease.
– may present as an acute hepatitis.
38. Hepatitis D Virus Modes of
Transmission
Percutaneous exposures
injecting drug use
Per mucosal exposures
sex contact
39. HBV - HDV
Coinfection Course
Typical Serologic
Symptoms
ALT
Elevated
Titre
IgM anti-HDV
anti-HBs
HDV RNA
HBsAg
Total antiHDV
Time after Exposure
40. HBV - HDV
Typical Serologic
Superinfection Course
Jaundice
Symptoms
Titre
Total anti-HDV
ALT
HDV RNA
HBsAg
IgM anti-HDV
Time after
41.
42. Hepatitis D - Prevention
HBV-HDV Co-infection
Pre or post-exposure prophylaxis to prevent
HBV infection.
HBV-HDV Super-infection
Education to reduce risk behaviors among
persons with chronic HBV infection.