Different hepatitis C virus dynamics of free-virions and immune-complexes after initiation of interferon-α in patients with chronic hepatitis C

Background/Aims: To elucidate the mechanisms of action of interferon (IFN) against hepatitis C virus (HCV), we studied the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in patients treated with IFN. Methods: FV and IC were separated by immunoprecipitation using anti-human immunoglobulin and quantified serially using real-time detection-polymerase chain reaction. Results: Initially [1st phase (0–24 h)], the FV decreased more rapidly compared to IC [exponential decay slope (EDS)=1.78±0.42 vs. 0.99±0.31 log10/day, P<0.001; HALF-LIFE=5.65±2.02 vs. 12.5±2.83 h, P<0.0001], but at the 2nd phase (1–14 days), half-life of FV was significantly longer than that of IC (101±117 vs. 14.2±1.08 h, P<0.005). Regarding response to IFN, the decline slope was not significantly different at the 1st phase, but at the 2nd phase, the FV-HCV RNA decreased more slowly in non-responders than in sustained responders to IFN (EDS=0.05±0.02 vs. 0.34±0.19 log10/day, P<0.005; HALF-LIFE=186±112 vs. 15.3±1.85 h, P<0.005). Conclusions: The presence of escape mutants from the neutralizing antibodies may be involved in resistance to IFN. Analyzes of FV- and IC-HCV dynamics are useful for predicting the IFN efficacy and understanding the mechanism of IFN action in chronic hepatitis patients.