Hepatitis B Surface Antigen (HBsAg) Assays—Are They Good Enough for Their Current Uses?

Abstract

Hepatitis B virus (HBV) is the most common significant chronic viral infection world-wide. Approximately 350–400 million people have active HBV infections, and as many as one third of the world’s population has evidence of exposure to HBV. Spread of the virus occurs primarily through contact with infected serum, sexual contact with infected individuals, and vertical transmission from mother to infant. Since shortly after its discovery as the “Australia antigen” (1), hepatitis B surface antigen (HBsAg) has been the principal target for laboratory testing to identify active infection by HBV. Accumulating evidence, including the article by Chen and Kaplan (2) in this issue of Clinical Chemistry , calls into question the degree to which HBsAg assays can be used as the “gold standard” for detecting HBV infection. The increasing availability of automated assays for viral markers on instruments traditionally found in immunochemistry laboratories makes it imperative for those working in such laboratories to be familiar with issues in HBsAg testing. Exposure to HBV has a variable outcome that is largely determined by the age and immune status of an infected individual. In healthy adolescents and adults, the most common population exposed to HBV in northern Europe and most of North America, exposure to HBV typically leads to acute hepatitis, followed by loss of detectable HBsAg and loss of circulating HBV DNA (as measured by most assays). Chronic infection, identified by persistence of HBsAg, may follow infections in infants, persons with immunosupression, and a small number of otherwise healthy individuals. Such chronic infection may be associated with active viral replication (detected by circulating HBV DNA), or with “nonreplicating” infection, in which HBsAg continues to be produced but HBV DNA is undetectable (by most assays) in the circulation. Replicating forms of infection can convert to nonreplicating forms, either spontaneously (5%–10%/year) or after treatment …