Dynamics of regulatory T cells and plasmacytoid dendritic cells as immune markers for virological response in pegylated interferon-α and ribavirin therapy for chronic hepatitis C patients

For the treatment of chronic hepatitis C, a combination of pegylated interferon-alpha (PEG-IFN alpha) and ribavirin has been widely used as a standard of care. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. Our aim was to elucidate whether or not the frequency or function of blood cells is related to the outcome of the therapy. Sixty-seven chronic hepatitis C patients with high viral load of HCV genotype 1 infection who underwent 48 weeks of PEG-IFN alpha 2b and ribavirin therapy were examined. During the treatment, frequencies of myeloid or plasmacytoid dendritic cells, Th1, Th2 cells, NK cells, and regulatory T cells were phenotypically determined. Among the patients enrolled, 29 showed a sustained virological response (SVR), 18 a transient response (TR) and 17 no response (NR). The clinical and immunological markers were compared between the SVR and non-SVR patients, including TR and NR. Based on clinical, histological, immunological parameters, and cumulative dosage of PEG-IFN alpha 2b and ribavirin, multivariate analyses revealed that higher platelet counts and higher regulatory T cell frequency at week 12 are indicative of SVR. Even in patients who attained complete early virological response at week 12, multivariate analyses disclosed that higher platelet counts and higher plasmacytoid dendritic cell frequency are indicative of SVR. In PEG-IFN alpha and ribavirin combination therapy for chronic hepatitis C patients, the increments of regulatory T cells and plasmacytoid dendritic cell frequency are independently related to favorable virological response to the therapy.