Diagnostic Tests for Hepatitis C: Where Are We Now?

Non-A, non-B hepatitis was recognized during the early 1970s in studies of transfusion-associated hepatitis through detection of abnormal serum enzyme levels, especially alanine aminotransferase (ALT) [1-3]. The primary cause for the illness was not established until 1989, when hepatitis C virus (HCV) was identified by molecular cloning techniques [4, 5]. Diagnostic tests for HCV were developed soon after the disease was identified, the first of which was directed at detecting antibody to a single epitope that had been cloned as a fusion protein (5-1-1) on an enzyme-linked immunosorbent assay (ELISA) format [4]. Although a critical first step, the test had poor sensitivity, delayed appearance of antibody to hepatitis C (anti-HCV) after acute infection, and a substantial frequency of false-positive results [6]. The latter problem was only partially overcome by the development of a supplementary recombinant strip immunoblot assay (RIBA) that is based on the detection of anti-HCV antigens immobilized on membranes; with this assay, nonspecific binding of serum immunoglobulins onto antigen-coated microwells is avoided [7]. However, to further improve sensitivity and specificity, second-and third-generation ELISAs and RIBAs were devised through modification of previously used antigens and the incorporation of an increasing number of new HCV antigens in each succeeding assay. The third-generation format has not yet been approved for commercial use in the United States.