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 hepatitis C virus have been suggested to be a cause of persistent infection by providing a way for the virus to escape host immunity. However, the variation rate in the hypervariable region is often low in patients with chronic hepatitis. The aim of this study was to elucidate the mechanism of persistent infection in patients with chronic hepatitis by investigating the relationship between the antibody response to and the variation in hypervariable region. Methods: The hypervariable regions of 26 clones of six patients with chronic hepatitis C were expressed as proteins fused with glutathione Stransferase, and sera of the patients were serially tested for antibody to these proteins. Results: The extent of antibody response to the hypervariable region differed considerably among the patients. Three patients showed no or only scanty antibody response. These had a lower variation rate in the hypervariable region (0-1.3/year) than in the others with frequent or persistent antibody response (2.1-14.6/year). In two patients, serum samples were found to be reactive with the clones even before the appearance of the clones. In three patients, coexistence of the antibodies and corresponding 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.