Approximately 10% of chronic hepatitis C patients who were treated with interferon have a sustained normalization of aminotransferase levels after interferon therapy without HCV RNA clearance. We investigated genetic change in hypervariable region 1 (HVR 1) to see if the mutation in this region is responsible for their sustained biochemical response and relapse thereafter. A total of 250 patients with chronic hepatitis C who were treated with interferon were studied for 8 to 11 years post therapy. Of these, 26 were biochemical responders (BR) whose ALT remained normal without viral clearance for more than 6 months after IFN therapy. HVR 1 was examined by direct sequencing of the PCR products, and found that no significant HVR 1 differences were observed in samples obtained pretreatment, posttreatment or during flares from these patients, suggesting that mutations in this region were not responsible for either the persistence of the HCV RNA or for the ALT relapses thereafter.