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Topic Outline
INTRODUCTION
The diagnosis of hepatitis B virus (HBV) infection was revolutionized by the discovery of Australia antigen, now called hepatitis B surface antigen (HBsAg). During the ensuing two decades, serologic assays were established for HBsAg and other HBV antigens and antibodies. Advances in molecular biology techniques led to the development of hybridization and polymerase chain reaction (PCR) assays for direct determination of hepatitis B virus DNA (HBV DNA). The diagnosis of HBV infection can also be made by the detection of HBsAg or hepatitis B core antigen (HBcAg) in liver tissues by immunohistochemical staining and of HBV DNA by Southern hybridization, in-situ hybridization, or PCR.
This topic review will focus on the changes in hepatitis B antigens, antibodies, and DNA levels that occur during acute and chronic infection and how these tests can be used clinically. A diagnostic algorithm will be presented for using these tests to diagnose acute hepatitis, past infection, and chronic infection.
SEROLOGIC MARKERS
Infection with HBV is associated with characteristic changes in the serum levels of hepatitis B antigens and antibodies (table 1A-B and figure 1). These markers are used to define different clinical states (table 2).
Hepatitis B surface antigen and antibody — Hepatitis B surface antigen (HBsAg) is the serologic hallmark of HBV infection. It can be detected by radioimmunoassays (RIA) or enzyme immunoassays (EIA).
HBsAg appears in serum 1 to 10 weeks after an acute exposure to HBV, prior to the onset of hepatitic symptoms or elevation of serum alanine aminotransferase (ALT) (figure 1). In patients who subsequently recover, HBsAg usually becomes undetectable after four to six months. Persistence of HBsAg for more than six months implies chronic infection. It is estimated that less than 1 percent of immunocompetent adult patients with genuine acute hepatitis B progress to chronic infection [1]. Among patients with chronic HBV infection, the rate of clearance of HBsAg is approximately 0.5 percent per year [2].
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