Current issues in the diagnosis of hepatitis B and C virus infections.
Diagnostic tests for hepatitis B virus infection are well established, although development of format and components continues. Variants of HBV with amino acid changes in the major antigenic determinant of the surface protein (HBsAg), and which may escape neutralisation by anti-HBs, have been described in many countries. The increasing reliance on monoclonal antibodies in the formulation of new assays for HBsAg raises the question of whether these surface variants may escape detection. The prevalence of variants which are unable to synthesise the e antigen (precor mutants), especially in certain geographical areas, means that the absence of HBeAg in carriers, with or without anti-HBe, does not necessarily indicate clearance of viraemia. The discovery of hepatitis C virus was followed rapidly by evidence of considerable sequence variation among different isolates. At least six major genotypes of HCV are recognised worldwide. Nonetheless, current assays seem reliable for detection of antibodies to this diverse virus. Assays for antigen are not available and diagnosis of viraemia requires sensitive detection of the viral genome, for example using reverse transcription and the polymerase chain reaction (RT-PCR). Evaluation of the efficacy of anti-viral therapy requires quantitative assays, adding a further degree of complexity. Other tests, such as the branch DNA (bDNA) assays are available, but lack sensitivity. Whether different genotypes of HCV vary in their pathogenicity and response to therapy remains contentious and convenient methods for determination of the genotype (or equivalent serotyping assays) are required to resolve this issue.
Harrison
T J
TJ
Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK. tjh@rfhsm.ac.uk