Hepatitis C virus nonstructural protein specific T cells are associated with virological responses to combination therapy in chronic HCV patients.

BACKGROUND: Virus-specific T-cell responses play a major role in antiviral immune response. However, the effect of hepatitis C virus (HCV)-specific T-cell responses on combination therapy still remains controversial. AIMS: To identify the association between HCV-specific T cell responses and efficiency of combination therapy. METHODS: To address this issue, a longitudinal analysis of HCV-specific T-cell responses to overlapping peptides covering HCV-nonstructural protein (NS) was performed using ELISpot assay in 48 chronically infected HCV-1b patients during combination treatment with peginterferon-alfa and ribavirin. RESULTS: Fifty-two percent of chronic HCV patients showed detectable HCV-NS3, NS4 or NS5A specific T-cell responses before therapy, with NS3 appearing to be the most immunodominant protein followed by NS5A and NS4. In addition, the percentage of patients responding to peptide stimulation was higher in patients with sustained virological response (SVR) when compared with those without SVR. Dynamics of HCV-NS-specific T-cell responses were further analysed; we found that HCV-specific T-cell responses maintained higher levels at 12 weeks into treatment in patients with SVR. In contrast, HCV-specific T-cell responses in patients without SVR declined significantly at 4 weeks into treatment and maintained low levels at 12 weeks. CONCLUSION: We found that the HCV-specific T-cell responses were associated with good viral control in patients with combination therapy