Page 357 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART IV Clinical Virology
346
In chronic HBV infection, a carrier state occurs and
progeny HBV continues to be made. In this carrier state,
gen–antibody complexes cause some of the early symptoms
(e.g., arthralgias, arthritis, and urticaria) and some of the
most of the circular HBV DNA is found free in the nucleus
complications in chronic hepatitis (e.g., glomerulonephri-
as an episome. A small amount of HBV DNA is integrated
into host cell DNA. How episomal HBV DNA is main-
tis, cryoglobulinemia, and vasculitis).
tained in the carrier state for many years is unclear.
About 5% of adult patients with HBV infection become
Transmission & Epidemiology
become chronic carriers (see later). A chronic carrier is
someone who has HBsAg persisting in their blood for
The three main modes of transmission are via blood, dur- chronic carriers. In contrast, 90% of infected newborns
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6 months or longer. The chronic carrier state is attributed
ing sexual intercourse, and perinatally from mother to
to a persistent infection of the hepatocytes, which results
newborn. The observation that needle-stick injuries can
in the prolonged presence of HBV and HBsAg in the
transmit the virus indicates that only very small amounts of
blood are necessary. HBV infection is especially prevalent
the infection or becomes a chronic carrier is the adequacy
in addicts who use intravenous drugs. Screening of blood
of the cytotoxic T-cell response. HBV DNA exists primar-
for the presence of HBsAg has greatly decreased the num-
ily as an episome in the nucleus of persistently infected
3
ber of transfusion-associated cases of hepatitis B.
cells; a small number of copies of HBV DNA are integrated
However, because blood transfusion is a modern proce-
into cell DNA.
dure, there must be another, natural route of transmission.
A high rate of hepatocellular carcinoma (HCC) occurs
HBV is found in semen and vaginal fluids, so it is likely that
sexual transmission is important. Transmission from
because the HBx protein inactivates the p53 tumor sup-
mother to child during birth is another important natural
pressor protein (see Chapter 43). In addition, HCC may be
route. Transplacental transmission, if it occurs, is rare. in chronic carriers. The HBx gene may be an oncogene
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the result of persistent cellular regeneration that attempts to
There is no evidence that transmission of HBV occurs dur-
replace the dead hepatocytes. Alternatively, malignant
ing breast feeding.
transformation could be the result of insertional mutagen-
Note that enveloped viruses, such as HBV, are more
sensitive to the environment than nonenveloped viruses
the hepatocyte DNA. Integration of the HBV DNA could
and hence are more efficiently transmitted by intimate con-
activate a cellular oncogene, leading to a loss of growth
tact (e.g., sexual contact). Nonenveloped viruses, such as
control. Almost all HCC cells have HBV DNA integrated
HAV, are quite stable and are transmitted well via the envi-
into the cell DNA.
ronment (e.g., fecal–oral transmission).
Chronic carriage is more likely to occur when infection
Hepatitis B is found worldwide but is particularly preva-
lent in Asia. Globally, more than 300 million people are
newborn’s immune system is less competent than that of an
chronically infected with HBV, and about 75% of them are
adult’s. Approximately 90% of infected neonates become
Asian. There is a high incidence of hepatocellular carci-
chronic carriers. Chronic carriage resulting from neonatal
noma (hepatoma) in many Asian countries—a finding that occurs in a newborn than in an adult, probably because a
infection is associated with a high risk of HCC.
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indicates that HBV is a human tumor virus (see Chapter
43). Immunization against HBV has significantly reduced
Some chronic carriers make e antigen (they are said to
be e antigen positive) and therefore have a high probability
the incidence of hepatoma in children. It appears that the
HBV vaccine is the first vaccine to prevent a human
cancer.
disease. The e antigen is the indicator of transmissibility
because it is encoded by the same gene that encodes the
Pathogenesis & Immunity
core protein indicating that the HBV DNA genome is pres-
ent. Some chronic carriers do not make e antigen (they are
After entering the blood, the virus infects hepatocytes, and
said to be e antigen negative) and therefore have a low
viral antigens are displayed on the surface of the cells. Cyto-
probability of making infectious virions and are less likely
toxic T cells mediate an immune attack against the viral
antigens, and inflammation and necrosis occur. Immune
Lifelong immunity occurs after the natural infection
attack against viral antigens on infected hepatocytes is
and is mediated by humoral antibody against HBsAg. Anti-
mediated by cytotoxic T cells. The pathogenesis of hepatitis B to transmit the disease.
body against HBsAg (HBsAb) is protective because it binds
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is probably the result of this cell-mediated immune injury,
to surface antigen on the virion and prevents it from inter-
acting with receptors on the hepatocyte. Another way of
3
In the United States, donated blood is screened for HBsAg and antibod-
Note that antibody against the core antigen (HBcAb) is not
ies to HBcAg, HCV, HIV-1, HIV-2, and HTLV-1. Two other tests are also
performed: a VDRL test for syphilis and a transaminase assay, which, if
protective because the core antigen is inside the virion and
elevated, indicates liver damage and is a surrogate marker of viral
the antibody cannot interact with it.
infection.
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