Interferon resistance of hepatitis C virus

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Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are prdictive factors of poor response to interferon therapy in patients with chronic hepatitis C.However, few patients with low virus load and genotype 1b show poor response to treatment. To further examine the factors predicting the response to interferon therapy in patients with genotype 1b infection, we analyzed entire nucleotide sequences of HCV extracted from three non-responders and one responder. We were no able to identify any single amino acid mutation which determines the resitance to interferon. We also examined 57 consecutive patients who were treated with 624 million units of lymphoblastoid alpha-interferon. Multivariate analysis showed that pretreatment virus load and multiple amino acid substitutions in the ISDR significantly correlated with failure to eliminate the virus. Our data support the hypothesis that HCV without amino acid substitution in the ISDR is resistant to interferon treatment. However, polymerase chain reaction-based analysis of two responders with multiple amino acid substitutions in the ISDR revealed the presence of a small amount of wild type strain in their serum, suggesting that the wild type HCV is not resistant to interferon. The precise mechanism of anti-viral effect of interferon and its relationship with amino acid substitutions of the ISDR should be further investigated in order to develop a more effective anti-viral strategy.