Hepatitis b,c, &d

1. Hepatitis B, C & D Viruses
Dr. Masood Ahmad

2. Viral hepatitis B

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 )

4. Hepatitis B Virus

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- appear on the
Ⅰ
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 HLA-
on 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. Incubation period: Average 60-90 days
Range 45-180 days
Clinical illness (jaundice):<5 yrs, <10%
5 yrs, 30%-50%
Acute case-fatality rate:0.5%-1%
Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
Premature mortality from
chronic liver disease: 15%-25%
Hepatitis B - Clinical Features

11. Spectrum of Chronic Hepatitis B Diseases
1.Chronic Persistent Hepatitis - asymptomatic
2.Chronic Active Hepatitis - symptomatic
exacerbations of hepatitis
3.Cirrhosis of Liver
4.Hepatocellular Carcinoma

12. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
04812162024283236 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre

13. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0481216202428323652 Years
Weeks after
Exposure
Titre
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course

14. Symptomatic Infection
Chronic Infection
Age at Infection
Chronic Infection (%)
S
y
m
p
t
o
m
a
t
i
c

I
n
f
e
c
t
i
o
n

(
%
)
Birth 1-6 months7-12 months 1-4 yearsOlder Children
and Adults
0
20
40
60
80
100100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
C
h
r
o
n
i
c

I
n
f
e
c
t
i
o
n

(
%
)

15. 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
Global Patterns of Chronic HBV
Infection

17. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breast milk
Concentration of Hepatitis B
Virus in Various Body Fluids

18. 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.

Hepatitis B Virus
Modes of Transmission

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.

23. Hepatitis C Virus

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. Incubation period: Average 6-7 wks
Range 2-26 wks
Clinical illness (jaundice):30-40% (20-30%)
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective
antibody
response identified
Hepatitis C - Clinical Features

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. Symptoms
anti-
HCV
ALT
Normal
01234561234
Hepatitis C Virus Infection
Typical Serologic Course
Titr
e
Mont
hs
Years
Time after
Exposure

28. 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
Risk Factors Associated with
Transmission of HCV

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. Screening of blood, organ, tissue donors
High-risk behavior modification
Blood and body fluid precautions

Prevention of Hepatitis C

34. Hepatitis D (Delta) Virus

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.

36. HBsAg
RNA
d antigen
Hepatitis D (Delta)
Virus

37. 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.

Hepatitis D - Clinical Features

38. Percutaneous exposures
injecting drug use
Per mucosal exposures
sex contact

Hepatitis D Virus Modes of
Transmission

39. anti-HBs
Symptoms
ALT
Elevated
Total anti-
HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV
CoinfectionTypical Serologic Course
Time after Exposure
Titre

40. Jaundice
Symptoms
ALT
Total anti-HDV
IgM anti-HDV
HDV RNA
HBsAg
HBV - HDV
SuperinfectionTypical Serologic Course
Time after
Exposure
Titre

42. 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.

Hepatitis D - Prevention

43. Thanks