HEPATITIS B
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-HBsThis is the specific antibody to hepatitis B surface antigen. Its appearance 1 to 4 monthsafter onset of symptoms indicates clinical recovery and subsequent immunity to HBV.Anti-HBs can neutralize HBV and provide protection against HBV infection. |
| HBcAgHepatitis B core antigen is derived from theprotein 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-HBcThis is the specific antibody to hepatitis B coreantigen. Antibodies to HBc are of class IgM andIgG. 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. |
| HBeAgHepatitis 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 ofanti-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. HBeAg’s function is uncertain.
Its specific antibody is anti-HBe. |
anti–HBeThis is the specific antibody to hepatitis B eantigen. During the acute stage of infection theseroconversion from e antigen to e antibody is prognostic for resolution of infection. Its presence in the patient’s blood along withanti-HBc and in the absence of HBsAg, anti-HBsand 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 xantigen. 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-HBcDetermine level of infectivity with HBeAg or HBV DNA. |
| – | + | + | Indicates previous HBV infection and immunity to hepatitis B. |
| – | – | + | Possibilities include: past HBV infection; low-level HBVcarrier; 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 | IgG | IgM | HBeAg | 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 toantigen 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.
Hepatitis B virus serological markers in different stages of infection and convalescence.23, 31, 52
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 incarriers 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 anonimmunized 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 containantibodies against a variety of mutant proteins, if perfection is the goal.
Prevalence of hepatitis B in various areas
| % of population positive for | infection | |||
| Area | HBsAg | anti-HBs | neonatal | childhood |
| Northern, Western, and Central Europe,North America,Australia | 0.2-0.5 | 4-6 | rare | infrequent |
| Eastern Europe, theMediterranean,Russia and theRussian Federation,Southwest Asia, Central and South America | 2-7 | 20-55 | frequent | frequent |
| Parts of China, Southeast Asia, tropical Africa | 8-20 | 70-95 | very frequent | very frequent |
Source: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index3.html
HEPATITIS
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