Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon‐α

In interferon treatment of chronic hepatitis C patients, the biochemical and virological responses mostly parallel each other. However, some patients who show persistent ALT normalization display continued viremia after cessation of therapy. High‐density hepatitis C virus (HCV) particles, which are immune complex forms, are reported to be less infectious both in vitro and in vivo. To assess whether high‐density HCV contributes to the response discrepancies and to clarify the association with patient outcome, sera were examined from chronic hepatitis C patients who were treated with interferon‐α. This study included 10 sustained responders with viremia (SR + ve), 5 SR without viremia, 3 transient responders (TR), and 3 nonresponders (NR). The SR + ve patients were defined as those with continued ALT normalization and serum HCV‐RNA positivity at 24 weeks after therapy completion. Serum samples obtained before and 24 weeks after therapy were ultracentrifuged on 35% sucrose. The ratio between high‐density and low density HCV was determined by quantification of HCV‐RNA titers in the bottom and top fractions by competitive reverse transcription and by the polymerase chain reaction, and expressed as the bottom/top (B/T) ratio. The B/T ratios before therapy were 1:l in all groups of patients, and 1:l after therapy in TR and NR groups. Five out of 6 SR + ve patients who showed 1:1 ratio after the apy relapsed within 1 year. In contrast, all SR + ve patients whose ratios were 10‐100:1 continued to show ALT normalization. These findings demonstrate that patients who have high‐density HCV dominance after therapy show persistent ALT normalization despite viremia, which can be explained by predominance of the neutralized immune complex. © 1995 Wiley‐Liss, Inc.