Mutations in the non-structural protein 5A gene in patients with chronic hepatitis C virus 1b infection during repeated interferon treatment

It has been previously reported that the non-structural region 5A (NS5A) of the hepatitis C virus (HCV) includes an interferon sensitivity determining region (ISDR) and that amino acid substitutions in this region are closely associated with the response to interferon (IFN) treatment. We assessed th e clinical significance of serial changes of amino acid sequences in the IS DR during repealed IFN treatment in patients with chronic hepatitis C (geno type 1b), related to serum HCV RNA load. During treatment, additional amino acid substitutions in the ISDR were observed in four of eight patients (50 % 2/5 of complete responders (CR); 2/3 of non-responders (NR). However, com paring these amino acid substitutions to wild-type ISDR, the number of amin o acid mutations was limited to only one amino acid identified in two CRs. The virus load changed regardless of the amino acid substitutions in the IS DR during treatment, and the wild-type and intermediate type (with less tha n three amino acid substitutions) showed wide variations in virus load. The se data indicate that amino acid mutations in the ISDR. which indicate the switch to mutant-type do not occur easily even during repeated IFN treatmen t, and the additional amino acid substitutions in the ISDR are nor a sensit ive marker during repeated IFN treatment. In cases where virus load is used as a marker of response to repeated UN treatment, serial examinations are necessary to determine the precise virus load levels. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.