Hepatitis C virus variants and the role of genotyping.

Hepatitis C virus demonstrates considerable divergence in nucleotide sequence. This variation may affect virus detection, disease outcome, and the effectiveness of interferon treatment. For example, infection with genotype 1 is associated with a lower response rate to interferon treatment. Hepatitis C virus can be classified into six distinct types, comprising at least 74 different subtypes. Both types and subtypes are subject to geographical differences in distribution, presumably reflecting the epidemiological history of the virus. However, because this history may be blurred by migration and by commerce in blood products between regions, screening and typing assays must recognize both the major indigenous and more exotic virus genotypes. Little information exists about the role of virus sequence variation in screening for hepatitis C virus antibodies, but there is some evidence that the reactivity of current serological screening assays for hepatitis C virus is genotype dependent. In the future, screening assays may need to include antigens specific for different virus types or may need to be designed with regard to the particular types found in a certain area. Antigenic variation may also mean that an effective vaccine needs to be multivalent to protect against all genotypes present in a given region. There are several polymerase chain reaction-based methods of distinguishing between hepatitis C virus variants. These methods must be continually updated, however, as new sequence variants are discovered. Alternative genotyping assays are based on the host's serological response to virus infection, but these cannot distinguish between virus subtypes and are unsuitable for immunocompromised patients. As more countries are sampled, it is likely that more genotypes will be identified and this may help elucidate the origins of hepatitis C virus. Detailed epidemiological studies may delineate past and current routes of transmission.