INTERFERON THERAPY IN CHRONIC HEPATITIS-C VIRUS - EVIDENCE OF DIFFERENT OUTCOME WITH RESPECT TO DIFFERENT VIRAL STRAINS

The aim of the study was to assess the role of different viral strains of hepatitis C virus (HCV) in determining the outcome of the alpha-in terferon (IFN) therapy. Fifty-seven patients (34 from Italy and 23 fro m Japan) with HCV-positive liver disease were enrolled in the study. T he NS4 region of HCV was amplified in sera by ''nested'' polymerase ch ain reaction (PCR) using a primer pair synthesized according to the se quence of JK-1. The NS4 region was positive in 14 (41%) Italian and in 13 (56%) Japanese patients. In positive patients the sequence of the NS4 region was also obtained. Subsequently, HCV genotype was determine d in all patients by PCR amplification of the core region. All patient s received recombinant alpha2a-interferon (IFN), 6 million units 3 tim es a week for 1 month followed by 3 million units 3 times a week for 5 months. The patients were followed for 1 year after the end of treatm ent. At the end of the follow-up, 17 (30%) had sustained normal levels of serum alanine aminotransferase (ALT). The outcome of treatment was not correlated with race, age, sex, histology, and pretreatment ALT l evel, but was significantly (P < 0.00001) associated with the presence of both the NS4-JK-1 region and HCV type II. Among the 27 NS4-positiv e patients, only 1 patient (3.7%) achieved a complete response, wherea s the remaining 26 patients (96.3%) either were non-responders or rela psed after IFN was discontinued. In contrast, among the 30 NS4-JK-1-ne gative patients, 15 (53%) had a sustained remission. HCV genotyping sh owed type I in 3 (6%), type II in 40 (74%), type III in 4 (7%), and ty pe IV in 3 (6%) cases. Coinfection was present in 4 (7%), while in 3 c ases amplification was not obtained. Patients with type II were all no n-responders or relapsers, while a response to the treatment was obser ved in 17 of 17 (100%) of the remaining patients. These data indicate that the presence of JK-1 variant of HCV or HCV type II is almost alwa ys predictive of a poor response rate of IFN therapy. (C) 1995 Wiley-L iss, Inc.