Different hepatitis C virus dynamics of free-virions and immune-complexes after initiation of interferon-alpha in patients with chronic hepatitis C.
OBJECTIVE
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.
Fujita
Naoki
N
Third Department of Internal Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
Kaito
Masahiko
M
Takeo
Masaki
M
Horiike
Shinichiro
S
Tanaka
Hideaki
H
Ikoma
Jiro
J
Watanabe
Shozo
S
Adachi
Yukihiko
Y
D000328:Adult; D000936:Antigen-Antibody Complex; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014771:Virion / Q000276:immunology
D000936:Antigen-Antibody Complex; D000998:Antiviral Agents; D004279:DNA, Viral; D016898:Interferon-alpha