SERIAL DENSITY ANALYSIS OF HEPATITIS-C VIRUS PARTICLE-POPULATIONS IN CHRONIC HEPATITIS-C PATIENTS TREATED WITH INTERFERON-ALPHA

In interferon treatment of chronic hepatitis C patients, the biochemic al and virological responses mostly parallel each other. However, some patients who show persistent ALT normalization display continued vire mia after cessation of therapy. High-density hepatitis C virus (HCV) p articles, which are immune complex forms, are reported to be less infe ctious both in vitro and in vivo. To assess whether high-density HCV c ontributes to the response discrepancies and to clarify the associatio n with patient outcome, sera were examined from chronic hepatitis C pa tients who were treated with interferon-cu. This study included 10 sus tained responders with viremia (SR + ve), 5 SR without viremia, 3 tran sient responders (TR), and 3 nonresponders (NR). The SR + ve patients were defined as those with continued ALT normalization and serum HCV-R NA positivity at 24 weeks after therapy completion. Serum samples obta ined before and 24 weeks after therapy were ultracentrifuged on 35% su crose. The ratio between high-density and low-density HCV was determin ed by quantification of HCV-RNA titers in the bottom and top fractions by competitive reverse transcription and by the polymerase chain reac tion, and expressed as the bottom/top (B/T) ratio. The B/T ratios befo re therapy were 1:1 in all groups of patients, and 1:1 after therapy i n TR and NR groups. Five out of 6 SR + ve patients who showed 1:1 rati o after-therapy relapsed within 1 year. in contrast, all SR + ve patie nts whose ratios were 10-100:1 continued to show ALT normalization. Th ese findings demonstrate that patients who have high-density HCV domin ance after therapy show persistent ALT normalization despite viremia, which can be explained by predominance of the neutralized immune compl ex. (C) 1995 Wiley-Liss. Inc.