Long-term response to interferon alpha is unrelated to "interferon sensitivity determining region" variability in patients with chronic hepatitis C virus-1b infection

Background/Aims: Contradictory data Have been reported about the predictive value of the variability in interferon sensitivity determining region (ISD R) of hepatitis C virus (HCV) genotype-lb on response to interferon-alpha I FN-alpha therapy. The aim of this study was to examine this issue in a seri es of patients with long-term response to IFN treatment. Methods: We retrospectively analyzed 24 patients with chronic HCV genotype- lb infection. treated with IFN-a (total dose median 677, range 216-1350 MU) selected in 6 Italian Liver Units. These:patients were defined as true lon g-term responders (LTR) since they showed persisting biochemical and virolo gical responses to IFN treatment (mean follow-up 38 months). HCV genomes fr om pretreatment serum samples were amplified and directly sequenced, The IS DR amino-acid sequences obtained were aligned and compared with the publish ed sequence of HCV-J. Results: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218, Fourteen patie nts showed only one mutation (at codon 2218), two had 2, five had 3, one ha d 4 and one had 5 mutations. When we compared the ISDR sequences from the 2 4 LTR with those of non-responders (NR), we found no significant correlatio n between the number of mutations and the response to therapy. Conclusions: Our results demonstrate that the persisting efficacy of IFN tr eatment in patients with chronic HCV is not related to the number of ISDR a mino acid susbstitutions of the infecting viruses. Further studies are need ed to verify whether other NS5A sequences outside the ISDR might be involve d in the mechanisms of IFN resistance.