Relationship between early HCV kinetics and T-cell reactivity in chronic hepatitis C genotype 1 during peginterferon and ribavirin therapy

Background/Aims 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 μg/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 (ε) than slow responders (SR) (84.5±3.2 vs. 65.2±7.0%, P=0.002), and a higher rate of infected cell loss (δ) (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.