Relationship between early HCV kinetics and T-cell reactivity in chronic hepatitis C genotype 1 during peginterferon and ribavirin therapy.
OBJECTIVE
To gain understanding of inter-individual differences of treatment response in hepatitis C virus genotype 1 (HCV-G1) patients, we investigated simultaneously the early HCV kinetics and virus-specific T-cell reactivity.


METHODS
Thirty, treatment-naïve HCV-G1 patients received peginterferon-alfa2a 180 microg/week plus ribavirin 1000-1200 mg/day, with blood samples collected prospectively at protocol time-points. HCV RNA was quantitated with a TaqMan assay with mathematical modelling of HCV decay. Virus-specific CD4+/CD8+ T-cells were enumerated by Elispot assays.


RESULTS
HCV kinetic analysis identified two subgroups: fast (18/30) and slow (12/30) treatment-responders. Although these subgroups did not differ in any baseline characteristics, fast responders (FR) showed greater antiviral efficacy (epsilon) than slow responders (SR) (84.5+/-3.2 vs. 65.2+/-7.0%, P=0.002), and a higher rate of infected cell loss (delta) (0.56+/-0.2 vs. 0.04+/-0.02, P=0.038). The viral load drop (baseline to treatment week 4) was higher in FR vs. SR group (3.5+/-1.1 vs. 1.4+/-0.6 log10IU/mL, P<0.001). T-cell reactivity to HCV increased only in FR (after the loss of viraemia), but not in SR patients.


CONCLUSIONS
Assessment of early viral and T-cell kinetics during treatment reveals marked differences amongst HCV-G1 patients and may provide a basis for treatment individualization. Enhancement of antiviral T-cell reactivity requires rapid viraemia clearance, rather than immunostimulation alone.
Tang
Kwok H
KH
Institute of Hepatology, University College London, 69-75 Chenies Mews, London. WC1E 6HX, UK.
Herrmann
Eva
E
Cooksley
Helen
H
Tatman
Nick
N
Chokshi
Shilpa
S
Williams
Roger
R
Zeuzem
Stefan
S
Naoumov
Nikolai V
NV
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000276:immunology; D019562:Viral Load; D014766:Viremia
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D012254:Ribavirin