Download Epidemiology and transmission

Hepatitis B
Properties:
HBV is a member of hepadnavirus family. It is 42 nm enveloped virion
(also known as "Dane particles") contain a partially circular doublestranded DNA genome. The envelope contains a protein called surface
antigen (HBsAg). Within the core is a DNA-dependent DNA polymerase.
Also there are two other antigens: core antigen (HBcAg) and e antigen
(HBeAg). Electron microscopy of HBsAg-positive serum reveals three
morphologic forms (figure 1). The most numerous are spherical particles
measuring 22 nm in diameter and small particles are made up
exclusively of HBsAg––as are tubular or filamentous forms, which have
the same diameter but may be over 200 nm long.
Figure (1): Hepatitis B virus.
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Replication:
After the HBV has attached to the cell surface receptor, the viral
membrane fuses with the cell membrane releasing the core into the
cytoplasm. The core proteins dissociate from the partially double
stranded DNA. DNA polymerase now completes the DNA so that it is
completely double stranded. The double stranded DNA enters the
nucleus and the viral DNA associates with host nuclear histones, then it
is transcribed by cellular RNA polymerase II into mRNAs. In contrast to
the situation with retroviruses, however, the DNA form of HBV is usually
not integrated into cellular DNA. The mRNA codes for the polymerase
and core HBcAg and HBeAg proteins. Inside the core, the RNA is
transcribed to minus strand DNA by the same DNA polymerase (reverse
transcriptase) that completed the double stranded DNA. The virus now
buds through the endoplasmic reticulum and/or Golgi Body membranes
(or perhaps a novel pre-Golgi compartment) of the host cell from which
it acquires HBsAg. At this stage or later, the minus stand of DNA is partly
transcribed into a plus strand. When the viral DNA polymerase is used to
transcribe RNA to DNA, it is acting as a reverse transcriptase similar to
that found in retroviruses; in fact, HBV DNA polymerase and retroviral
reverse transcriptase are very similar, and may have evolved from a
common ancestor.
Epidemiology and transmission:
World-wide in distribution, there are 450 million persistent carriers of
hepatitis B, 50 million of which are in Africa. Carriage rates vary
markedly in different areas. There are three mains mode of transmission
are: via blood (blood transfusions, serum products, sharing of needles,
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razors, acupuncture and organ donation); sexual intercourse and
horizontal transmission (in children, families, 'close personal contact) or
vertical transmission (perinatal transmission from a carrier mother to
her baby).
Pathogenesis
Infection is parenterally transmitted. The virus replicates in the liver and
virus particles, as well as excess viral surface protein, are shed in large
amounts into the blood. Viraemia is prolonged and the blood of infected
individuals is highly infectious. Following acute infection, approximately
5% of infected individuals fail to eliminate the virus completely and
become persistently infected. The virus persists in the hepatocytes and
on-going liver damage occurs because of the host immune response
against the infected liver cells.
Chronic infection may take one of two forms:
Chronic persistent Hepatitis - the virus persists, but there is minimal liver
damage
Chronic Active Hepatitis - There is aggressive destruction of liver tissue
and rapid progression to cirrhosis or liver failure.
Patients who become persistently infected are at risk of developing
hepatocellular carcinoma (HCC).
Clinical Features:
Insidious onset of symptoms tends to cause a more severe disease than
Hepatitis A. Many HBV infections are asymptomatic infections. The
incubation period is 10-12 weeks. The clinical appearance of acute
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hepatitis B tends to be sever, and life threatening hepatitis can occur
(figure 2).
Symptoms
anti-HBe
HBeAg
Total anti-HBc
Titre
0
4
anti-HBs
IgM anti-HBc
HBsAg
8
12 16 20 24 28 32 36
52
100
Weeks after Exposure
Figure (2): acute hepatitis B with recovery (typical serological course).
Diagnosis:
Serological tests are used for the diagnosis of acute and chronic hepatitis
B infection.
 HBsAg - used as a general marker of infection.
 HBsAb - used to document recovery and/or immunity to HBV
infection, is not found in chronic carriers.
 Anti-HBc IgM - marker of acute infection.
 Anti-HBcIgG - past or chronic infection.
 HBeAg - indicates active replication of virus and therefore
infectiveness.
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 Anti-Hbe - virus no longer replicating. It indicates low infectivity in
a carrier.
Treatment and prevention:
Alpha interferon is clinically useful for the treatment of chronic active
hepatitis. Lamivudine - a nucleoside analogue reverse transcriptase
inhibitor, reduce hepatic inflammation and lower the levels of HBV in
chronic carriers.
Prevention by; highly effective recombinant vaccines are now
available, or hepatitis B immunoglobulin - HBIG may be used to
protect persons who are exposed to hepatitis B.
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