DEFICIENCY OF ANTIBODY-RESPONSE TO HYPERVARIABLE REGION OF HEPATITIS-C VIRUS IN PATIENTS WITH CHRONIC HEPATITIS-C

Background/Aims: Frequent mutations in the hypervariable region of hep atitis C virus have been suggested to be a cause of persistent infecti on by providing a way for the virus to escape host immunity. However, the variation rate in the hypervariable region is often low in patient s with chronic hepatitis. The aim of this study was to elucidate the m echanism of persistent infection in patients with chronic hepatitis by investigating the relationship between the antibody response to and t he variation in hypervariable region. Methods: The hypervariable regio ns of 26 clones of six patients with chronic hepatitis C were expresse d as proteins fused with glutathione S-transferase, and sera of the pa tients were serially tested for antibody to these proteins. Results: T he extent of antibody response to the hypervariable region differed co nsiderably among the patients. Three patients showed no or only scanty antibody response. These has a lower variation rate in the hypervaria ble region (0-1.3/year) than in the others with frequent of persistent antibody response (2.1-14.6/year). In two patients, serum samples wer e found to be reactive with the clones even before the appearance of t he clones. In three patients, coexistence of the antibodies and corres ponding clones were noted. An augmentation of antibody response always followed rises in serum alanine aminotransferase levels. Conclusion: Deficiency of antibody response to the hypervariable region may be one of the causes of persistency in hepatitis C virus infection.