Time-related changes in full-length hepatitis C virus sequences and hepatitis activity

The activity of hepatitis Varies in chronic hepatitis C virus (HCV) infecti on. Some patients show persistently normal serum alanine aminotransferase ( ALT) values, whereas the others show high-ALT values and progress to liver cirrhosis or hepatocellular carcinoma. However, virological mechanisms caus ing hepatitis have not fully been elucidated. We analyzed serial changes in full-length HCV sequences in 10 patients with various profiles of hepatiti s activity. In the nonstructural 5A (NS5A) and NS5B, the rate of amino acid changes,as well as the proportion of nonsilent ones, was low in patients w ith normal ALT values compared with those with abnormal ALT (for the rate o f amino acid changes, 0 x 10(-3) vs 3.19 x 10(-3) changes/site/year (P = 0. 037) in NS5A and 0 x 10-3 vs 1.22 x 10-3 changes/site/year (P = 0.023) for NS5B, for the proportion of nonsilent changes, 4 vs 22% (P = 0.017) in NS5A and 0 vs 16% (P = 0.039) in NS5B). Also, the flare-up of hepatitis coincid ed with higher nucleotide/amino acid substitution rates in NS5B. In conclus ion, the genomic structures of the NS5A and NS5B regions may correlate with hepatitis activity in chronic hepatitis C. (C) 1999 Academic Press.