Review
Occult hepatitis B

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Summary

Worldwide, chronic hepatitis B virus (HBV) infection is the primary cause of cirrhosis and hepatocellular carcinoma and is one of the ten leading causes of death. Traditionally, people with chronic HBV infection have been identified with blood tests for HBV antigens and antibodies. Recently, another group of patients with chronic HBV infection has been identified by sensitive, molecular testing for HBV DNA. Members of this group are often referred to as having occult hepatitis B because they are HBV-DNA positive, but hepatitis B surface antigen negative. Occult hepatitis B occurs in a number of clinical settings. In this review, we examine occult hepatitis B in people co-infected with hepatitis C, in whom occult hepatitis B has been associated with advanced fibrosis and diminished response to interferon α. Although much more research is needed, existing reports justify a heightened awareness of the medical importance and means of testing for occult hepatitis B.

Section snippets

Overview

Individuals with occult hepatitis B by definition are HBsAg negative. HBeAg is detectable only rarely. Individuals are variably positive for surface and core antibody, though about 20% are negative for all markers of past HBV infection aside from HBV DNA. Since viral DNA levels in occult hepatitis B are very low, the identification of occult hepatitis B is strongly dependent on both the sensitivity and specificity of the assay.

Whereas this is generally true for all laboratory-based diagnoses,

Overview

Although the presence of occult hepatitis B in chronic HCV infection is well established, the clinical relevance is still being assessed. Nevertheless, occult hepatitis B has been associated with advanced fibrosis/cirrhosis in cross-sectional studies and with poor interferon α response in several treatment studies (table 6). Occult hepatitis B has likewise been reported in a high proportion of HCV-infected patients who develop hepatocellular carcinoma. Although only limited clinical and

Possible mechanisms

The molecular/immunological mechanisms underlying occult hepatitis B infection remain incompletely defined and are probably multifactorial. On the one hand, occult hepatitis B could merely show the greater sensitivity of the PCR-based testing used to detect HBV DNA, compared with the enzyme immunoassay tests used to detect serum antigens. In some cases, mutations in the hepatitis B surface gene could substantially reduce the sensitivity of the HBsAg assays by making the surface protein less

Conclusions

Occult hepatitis B is defined by the presence of HBV DNA in the serum or liver of people without HBsAg. Occult hepatitis B can be identified in a substantial subset of HCV-infected people, especially in those who are positive for HBcAb. Serum HBV DNA levels are characteristically low, but despite the low replication rate, HBV DNA detection can be associated with ALT flares and is associated with advanced fibrosis/cirrhosis. In addition, occult hepatitis B is associated with decreased interferon

Search strategy and selection criteria

Data for this review were obtained by searching Medline using the terms “occult hepatitis B” as well as the related terms: “inapparent HBV infection”, “serologically silent hepatitis B”, “silent hepatitis B”, and “surface antigen negative carriers”. Only English language articles were selected. Article abstracts were then reviewed to identify studies in HCV-infected patients. In addition, reference lists of the selected articles were examined to identify additional studies. References

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