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 group) were treated with interferon-alpha (IF-alpha). Dosage was six million units per day for one week and then three times a week for another six months. Seven HCV-infected patients (control group) did not receive IF-alpha therapy. The hypervariable region (HVR) of HCV in the sera of patients was amplified by reverse transcription-polymerase chain reaction (RT-PCR), and the variation of amino acid sequence in this region was determined. Serum alanine aminotransferase (ALT) activities in five patients treated for six months with IF-alpha fell to the normal range, when HCV was not detected in the sera of three patients. The nucleotide sequence variation in HVR of HCV in the sera of five patients who responded well to the IF-alpha therapy was relatively less than that in another five patients who did not respond to IF-alpha therapy and those in the control patients. These results indicate that the effectiveness of IF-alpha therapy was related to the sequence variation of HVR of HCV. This may have resulted from the selection pressure by humoral 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.