Hepatitis C virus (HCV) genotype 1b sequences from fifteen patients with hepatocellular carcinoma: the ‘progression score’ revisited

The genome of hepatitis C virus (HCV) associated with hepatocellular carcinoma (HCC) may have some characteristics which would barely be found in those of HCV from asymptomatic carriers (ASC). We analyzed 15 HCC patients who were infected with HCV genotype 1b (HCV-1b) for complete nucleotide sequences of the viral genomes. Of the 15 isolates, three were sequenced up to the first nucleotide of the 5′UTR, and six were sequenced to encompass the X-tail at the 3′ end: sequencing of at least three-quarters of the 5′UTR and entire polyprotein-ORF was accomplished in all 15 isolates. Analyses of these sequences together with those reported previously by Nagayama et al. [Hepatology; 31 (2000) 745] suggested that nine residues (nt 119 of 5′UTR and aa 90, 434, 938, 962, 1176, 1412, 2143, and 2774 of polyprotein) might be useful to discriminate HCC-type sequences from ASC-type ones. The ‘progression score’ was 1.4±0.9 in ASC versus 3.7±1.5 in HCC ( P=3.87E-07) when calculated with the Nagayama et al.'s seven residues, but was 1.4±0.6 versus 4.6±1.9 ( P=1.33E-09) with our nine residues: a greater difference between HCC and ASC was achieved in the latter system. Further analyses, by increasing the sample size and/or by extending the comparison to include entire 5′UTR and 3′UTR/X-tail, may thus contribute to define the ‘progression score’ more appropriately.