The clinical significance of reactivity to individual epitopes of the hepatitis C viral genome

In order to analyze the clinical significance of the various HCV epitopes, we compared the results of different HCV specific assays with HCV-RNA, determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 93% were positive for C22-3, 96% for C33C, 81% for C100-3 and 91% for RT-PCR. Positivity rates for 537 healthy subjects were 1.7% for C100-3 and 2.9% for second generation anti-HCV. A total of 6 persons were positive for C22-3 but not C100-3; all were negative for HCV-RNA. In 11 of 30 patients treated with interferon and HCV-RNA became negative and remained so for more than 24 months. In these 11 sustained responders, C100-3 and C33C antibody declined progressively, but C22-3 antibody showed a little change after treatment by quantitative analysis. The discrepancy of changes to NS region and core region after interferon treatment is consistent with a different clinical significance of reactivities to these HCV epitopes. Thus negative reactivity to NS region but positive for core region among healthy subjects may indicate past infection with HCV. Presence of antibodies to NS epitopes is implicated in HCV replication, while core epitopes indicate both present and past HCV infection.