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Serological markers of HBV infection

During HBV infection, the serological markers vary depending on


whether the infection is acute or chronic.11, 23, 31

Antigens Antibodies

HBsAg
Hepatitis B surface antigen is the earliest
indicator of acute infection and is also
indicative of chronic infection if its presence
persists for more than 6 months. It is useful
for the diagnosis of HBV infection and for
screening of blood.
Its specific antibody is anti-HBs.


anti-HBs
This is the specific antibody to hepatitis B
surface antigen. Its appearance 1 to
4 months after onset of symptoms indicates
clinical recovery and subsequent immunity to
HBV. Anti-HBs can neutralize HBV and
provide protection against HBV infection.


HBcAg
Hepatitis B core antigen is derived from the
protein envelope that encloses the viral
DNA, and it is not detectable in the
bloodstream. When HBcAg peptides are
expressed on the surface of hepatocytes,
they induce an immune response that is
crucial for killing infected cells. The HBcAg is
a marker of the infectious viral material and it
is the most accurate index of viral
replication.
Its specific antibody is anti-HBc.

anti-HBc
This is the specific antibody to hepatitis B
core antigen. Antibodies to HBc are of class
IgM and IgG. They do not neutralize the
virus. The presence of IgM identifies an early
acute infection. In the absence of HBsAg
and anti-HBs, it shows recent infection. IgG
with no IgM may be present in chronic and
resolved infections. Anti-HBc testing
identifies all previously infected persons,
including HBV carriers, but does not
differentiate carriers and non-carriers.


HBeAg
Hepatitis B e antigen appearing during
weeks 3 to 6 indicates an acute active
infection at its most infectious period, and
means that the patient is infectious.
Persistence of this virological marker beyond
10 weeks shows progression to chronic
infection and infectiousness. Continuous
presence of anti-HBe indicates chronic or
chronic active liver disease. HBeAg is not
incorporated into virions, but is instead
secreted into the serum. Mutant strains of
HBV exist that replicate without producing
HBeAg. HBeAgs function is uncertain.
Its specific antibody is anti-HBe.

anti-HBe
This is the specific antibody to hepatitis B e
antigen. During the acute stage of infection
the seroconversion from e antigen to e
antibody is prognostic for resolution of
infection. Its presence in the patients blood
along with anti-HBc and in the absence of
HBsAg, anti-HBs and core HBV mutants
indicates low contagiousness and
convalescence. 31


HBxAg
Hepatitis B x antigen is detected in HBeAg
positive blood in patients with both acute and
chronic hepatitis. HBxAg is a transcriptional
activator. It does not bind to DNA.
Its specific antibody is anti-HBx.


anti-HBx
This is the specific antibody to hepatitis B x
antigen. It appears when other virological
markers are becoming undetectable.



HBV DNA
HBV DNA is detectable by hybridization
assays or PCR as soon as 1 week after
initial infection. The tests are generally
performed for monitoring of antiviral
treatment or to detect mutants that escape
detection by current methods.



HBV DNA polymerase
Tests for the presence of HBV DNA
polymerase, detectable within 1 week of
initial infection, are only performed for
research purposes.




HBV serological markers in hepatitis patients


The three standard blood tests for hepatitis B can determine if a
person is currently infected with HBV, has recovered, is a chronic
carrier, or is susceptible to HBV infection.15, 23, 31
Assay results
Interpretation HBsAg anti-HBs anti-HBc

+


-


-


Early acute HBV infection

+


+/-

+

Acute or chronic HBV infection.
Differentiate with IgM-anti-HBc
. Determine level of infectivity with
HBeAg or HBV DNA.


Indicates previous HBV infection and
-

+ + immunity to hepatitis B.

-

-

+

Possibilities include: past HBV infection;
low-level HBV carrier; time span
between disappearance of HBsAg and
appearance of anti-HBs; or false-
positive or nonspecific reaction.
Investigate with IgM anti-HBc, and/or
challenge with HBsAg vaccine. When
present, anti-HBe helps validate the
anti-HBc reactivity.


-


-

-

Another infectious agent, toxic injury to
the liver, disorder of immunity,
hereditary disease of the liver, or
disease of the biliary tract.


-


+

-

vaccine-type response.


From: Hollinger FB, Liang TJ. Hepatitis B Virus. In: Knipe DM et al., eds. Fields
Virology, 4th ed., Philadelphia, Lippincott Williams &Wilkins, 2001:2971-3036,15
with permission (http://lww.com).
Interpretation of HBV serologic markers in patients with hepatitis.15
Serological test findings at different stages of HBV infection and in
convalescence


anti-HBc
Stage of infection HBsAg anti-HBs Ig
G
IgM HBeA
g
anti-
HBe

late incubation
period


+

-

-

-

+ or -

-

acute hepatitis B or
persistent carrier
state


+

-

+

+

+

-

HBsAg-negative
acute hepatitis B
infection


-

-

-

+

-

-

recovery with loss
of detectable anti-
HBs


-

-

+

-

-

-

healthy HBsAg

++

carrier

+ - + + or - - +

chronic hepatitis B,
persistent carrier
state


+

-

++
+

+ or -

+

-

HBV infection in
recent past,
convalescence


-

++

++

+ or -

-

+

HBV infection in
distant past,
recovery


-

+ or -

+
or
-

-

-

-

recent HBV
vaccination,
repeated exposure
to antigen without
infection, or
recovery from
infection with loss
of detectable anti-
HBc


-

++

-

-

-

-

From: Robinson WS. Hepatitis B virus and hepatitis D virus. In: Mandell GL,
Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 4th ed.
New York, Churchill Livingstone, 1995:1406-1439,31 with permission.

Discordant or unusual hepatitis B serological profiles requiring
further evaluation


Repeat testing of the same sample or possibly of an additional sample
is advisable when tests yield discordant or unusual results.15



HBsAg positive / anti-HBc
negative

An HBsAg-positive response is accompanied
by an anti-HBc negative reaction only during
the incubation period of acute hepatitis B,
before the onset of clinical symptoms and
liver abnormalities.


HBsAg positive / anti-HBs
positive / anti-HBc positive


Uncommon, may occur during resolution of
acute hepatitis B, in chronic carriers who
have serious liver disease, or in carriers
exposed to heterologous subtypes of HBsAg.


anti-HBc positive only


Past infection not resolved completely

HBeAg positive / HBsAg
negative

Unusual


HBeAg positive / anti-HBe
positive


Unusual


anti-HBs positive only in a
nonimmunized person


It may be a result of passive transfer of anti-
HBs after transfusion of blood from a
vaccinated donor, in patients receiving
clotting factors, after IG administration, or in
newborn children of mothers with recent or
past HBV infection.
Passively acquired antibodies disappear
gradually over 3 to 6 months, whereas
actively produced antibodies are stable over
many years.
Apparently quite common when person has
forgotten his/her immunization status!



Mutant proteins from mutant HBV strains may escape diagnostic
detection. The presence of different serological markers should
therefore be tested for a correct diagnosis. Diagnostic kits should
contain antibodies against a variety of mutant proteins, if perfection is
the goal.