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Interpretation of Hepatitis B Serologic Test Results


 Hepatitis B serologic testing involves measurement of several hepatitis B virus (HBV)-specific antigens and antibodies. Different serologic “markers” or combinations of markers are used to identify different phases of Hepatitis B Virus (HBV) infection and to determine whether a patient has acute or chronic HBV infection, is immune to HBV as a result of prior infection or vaccination, or is susceptible to infection.

Hepatitis B Surface Antigen (HBsAg)  is the most important serological marker for identifying infection with Hepatitis B Virus.

HBsAg is present early in acute infection, disappears with resolution of infection and persists in chronic infection.

IgM anti-HBc (IgM class antibody, against Hepatitis B Core Antigen) is essential for the diagnosis of acute infection, but is also seen occasionally in very active chronic hepatitis. Anti-HBc antibodies develop and persist after all HBV infections.

The loss of HBsAg and development of anti-HBc signals resolution of acute infection.

Anti-HBs also occurs post vaccination, but anti-HBc will not be present in such cases. Chronic infection is manifested by persistent HBsAg.

Markers of viral replication such as HBeAg and HBV-DNA (non-PCR method) are detectable during the early high replication phase, but are not detectable during the later quiescent low replication phase. HBeAg is not a reliable marker of HBV replication when a precore variant is responsible for the infection. Such cases will be HBeAg negative, anti-HBe positive, but HBV-DNA (by a non-PCR method) positive.

Antigen/Antibody tested
Test result
Inference
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Negative
Susceptible
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Positive
Immune due to natural infection
HBsAg
anti-HBc
anti-HBs
Negative
Negative
Positive
Immune due to hepatitis B vaccination
HBsAg
anti-HBc
IgM anti-HBc
anti-HBs
Positive
Positive
Positive
Negative
Acutely infected
HBsAg
anti-HBc
IgM anti-HBc
anti-HBs
Positive
Positive
Negative
Negative
Chronically infected
HBsAg
anti-HBc
anti-HBs
Negative
Positive
Negative
Interpreatation unclear; four possibilities:
1.       Resolved infection (most common)
2.       False-positive anti-HBc, thus susceptible
3.       “Low level” chronic infection
4.       Resolving acute infection
Hepatitis B surface antigen (HBsAg): A protein on the surface of hepatitis B virus; it can be detected in high levels in serum during acute or chronic hepatitis B virus infection. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. HBsAg is the antigen used to make hepatitis B vaccine.
Hepatitis B surface antibody (anti-HBs): The presence of anti-HBs is generally interpreted as indicating recovery and immunity from hepatitis B virus infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.
Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with hepatitis B virus in an undefined time frame.

IgM antibody to hepatitis B core antigen (IgM anti-HBc): Positivity indicates recent infection with hepatitis B virus. Its presence indicates acute infection.
Table source: DEPARTMENT OF HEALTH & HUMAN SERVICES Centers for Disease Control and Prevention Division of Viral Hepatitis