Genetic changes in the interferon sensitivity determining region of hepatitis C virus during the natural course of chronic hepatitis C

Amino acid mutations in the interferon sensitivity determining region (ISDR ) are closely associated with the response to interferon in patients with h epatitis C virus genotype Ib (HCV-lb) infection. In this study, 36 patients chronically infected with HCV-lb, with no history of interferon therapy wi th respect to ISDR changes in HCV were studied. Two serum samples were obta ined from each patient, with an average interval of 3.5 years, and predomin ant nucleotide and amino acid sequences of the ISDR at initial and subseque nt time points were com pa red for each patient. Three of 12 patients with the wild type ISDR (no amino acid mutation in the ISDR compared to the cons ensus sequence) changed to the intermediate type (1 to 3 mutations) at late r time points, whereas the other 9 still had the wild type. Similarly, 2 of 18 patients with the intermediate type changed to the wild type, whereas t he other 16 patients continued to have the intermediate type. One of 6 pati ents with the mutant type (4 or more mutations) changed to the intermediate type, and the other 5 continued to have the mutant type. Although ISDR nuc leotide changes/site/year were not significantly different among the 3 grou ps of patients, percentages of non-synonymous nucleotide changes were great er in the mutant type (63%) than the wild (9%) or the intermediate type (20 %) (P < 0.05). These results show that mutations in the ISDR do not occur f requently, suggesting that interferon sensitivity does not change greatly d uring the natural course of the disease in each patient. (C) 2000 Wiley-Lis s, Inc.