Advances in the molecular diagnosis of hepatitis C and their clinical implications.

Serologic assays for diagnosis of hepatitis C infection may yield indeterminate results despite improvements in sensitivity and specificity through second- and third-generation assays. Direct detection of hepatitis C virus (HCV) RNA based on qualitative reverse transcription-polymerase chain reaction or transcription-mediated amplification allows diagnosis in the early stages of acute infection and in patients unable to mount an antibody response. Quantitative HCV RNA assays are useful for selecting appropriate antiviral therapies, but until recently they have lacked comparability between tests. More sensitive qualitative assays should be used for determining duration of treatment or recognizing a sustained virologic response to therapy. Hepatitis C virus genotyping can be performed from a limited sequence analysis of the viral genome by using various techniques. Although newer genotyping methods are relatively practicable and are satisfactory for the discrimination of the majority of genotypes, discrimination between subtypes can be challenging. Serologic typing of HCV lacks sensitivity and specificity compared with molecular-based techniques. Recent advances in serologic assays and nucleic acid detection techniques allow physicians to make accurate diagnoses, and these assays serve as important tools in treatment planning.