cDNA Sequencing of the 5′ Noncoding Region (5′ NCR) to Determine Hepatitis C Genotypes in Patients with Chronic Hepatitis C

Reports suggest that response tointerferon-alpha therapy is influenced by both hepatitisC viral genotype and titer. Our aim was to determine ifdirect, automated, cycle sequencing of the PCR productfrom an HCV RNA detection assay could be used toreliably determine HCV genotype. In addition, theapproach was used to determine the HCV genotypedistribution in our patient population and to learn ifthere was a correlation between HCV genotype and RNAtiter that could be used to predict response totreatment. In all 143 consecutive patients were testedfor both HCV RNA titer and genotype. Automated, cycle sequencing of PCR product was highly effectiveand failed to yield a genotype in only 3 (2%) patients.The distribution of HCV genotypes was: 1a (40%), 1b(39%), 2a (2%), 2b (6%), 3a (4%). There were significant differences in the median HCV RNA titersbetween genotypes 1, 2, and 3. 6 High HCV RNA titers>4.4 × 106 copies/ml were only seenin genotype 1. However, the HCV RNA level should not beused as a surrogate marker of genotype because of a significantoverlap of titers within the genotypes.