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Reports suggest that response to interferon-alpha therapy is influenced by both hepatitis C viral genotype and titer. Our aim was to determine if direct, automated, cycle sequencing of the PCR product from an HCV RNA detection assay could be used to reliably determine HCV genotype. In addition, the approach was used to determine the HCV genotype distribution in our patient population and to learn if there was a correlation between HCV genotype and RNA titer that could be used to predict response to treatment. In all 143 consecutive patients were tested for both HCV RNA titer and genotype. Automated, cycle sequencing of PCR product was highly effective and 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 titers between genotypes 1, 2, and 3. High HCV RNA titers >4.4 x 10(6) copies/ml were only seen in genotype 1. However, the HCV RNA level should not be used as a surrogate marker of genotype because of a significant overlap of titers within the genotypes.