NUCLEOTIDE-SEQUENCE VARIATION IN THE HYPERVARIABLE REGION OF THE HEPATITIS-C VIRUS IN THE SERA OF CHRONIC HEPATITIS-C PATIENTS UNDERGOING CONTROLLED INTERFERON-ALPHA THERAPY

Ten patients with hepatitis C virus (HCV) infection (experimental grou p) were treated with interferon-alpha (IF-alpha). Dosage was six milli on units per day for one week and then three times a week for another six months. Seven HCV-infected patients (control group) did not receiv e IF-alpha therapy. The hypervariable region (HVR) of HCV in the sera of patients was amplified by reverse trancription-polymerase chain rea ction (RT-PCR), and the variation of amino acid sequence in this regio n was determined. Serum alanine aminotransferase (ALT) activities in f ive patients treated for six months with IF-alpha fell to the normal r ange, when HCV was not detected in the sera of three patients. The nuc leotide sequence variation in HVR of HCV in the sera of five patients who responded well to the IF-alpha therapy was relatively less than th at in another five patients who did not respond to IF-alpha therapy an d those in the control patients. These results indicate that the effec tiveness of IF-alpha therapy was related to the sequence variation of HVR of HCV. This may have resulted from the selection pressure by humo ral antibodies directed to HVR of HCV. It is concluded that the higher rate of sequence variation in HVR of HCV was compatible with a lower degree of effectiveness of IF-alpha therapy. (C) 1996 Wiley-Liss, Inc.