Characterization of anti-hepatitis C virus-positive sera not genotyped by restriction fragment length polymorphism or serology.

BACKGROUND: The hepatitis C virus genome is extremely heterogeneous and has been classified into six major genotypes. Genotyping of hepatitis C has been achieved through both direct molecular approach and indirect detection of host genotype-specific antibodies by serological methods. The purpose of this study was to characterize anti-hepatitis C positive sera samples that were not genotyped either by restriction fragment length polymorphism or by serology.
METHODS: Two hundred and two patients from northern California with established chronic hepatitis C virus infection were studied by restriction fragment length polymorphism analysis of the 5'-untranslated region amplicon. A serological genotyping assay, based on synthetic peptides derived from non-structural region 4 of the hepatitis C virus genome, was used to determine serological genotype.
RESULTS: Of the 202 patients studied, 187 (93%) were polymerase chain reaction-positive. One hundred and eighty-six patients were able to be genotyped by restriction fragment length polymorphism, compared with 144/202 (71%) of patients genotyped by serology (P < 0.0001). Only two of 202 samples showed discordant genotyping results. The distribution of hepatitis C virus genotypes in northern California was found to be type 1a, 41%; 1b, 35%; 2a, 3%; 2b, 10%; 3a, 11%; and 4, < 1%. There was no association between hepatitis C genotypes and age, gender distribution, ethnic origin, presumptive mode of transmission, serum alanine aminotransferase levels and the proportion of patients with cirrhosis. Of the 15 patients who were not genotypable by the molecular assay, four patients were genotyped by serology, with hepatitis C virus genotypes 1, 2 and 3 represented. Of the 58 samples that were not genotyped by serology, 47 were genotyped based on the molecular assay, and the distribution of hepatitis C virus genotypes was similar to that of the overall study population.
CONCLUSIONS: These data showed that: (i) molecular genotyping assay based on 5'-untranslated region is more sensitive than serologic genotyping based on the non-structural-4 region but the results were highly concordant; (ii) hepatitis C virus genotypes 1-4 are present in northern California, with genotype 1 being the most prevalent; and (iii) the failure to determine hepatitis C virus genotype based on molecular or serological genotyping assay does not appear to be related to specific hepatitis C genotypes.