Dynamic Changes in Ex Vivo T-Cell Function After Viral Clearance in Chronic HCV Infection

Abstract

Background. Direct-acting antiviral (DAA) agents can successfully treat chronic hepatitis C virus (HCV) infection. However, the ex vivo HCV-specific T-cell function following viral clearance remains unknown. Methods. We investigated functional alterations and phenotypic changes in ex vivo HCV-specific CD8(+) T cells with a longitudinal analysis of 41 patients with chronic HCV infection who were undergoing DAA treatment. Results. A patient subset exhibited a significantly increased T-cell response (mainly CD8(+) T cells) at week 4 of treatment. However, this increased T-cell response diminished in later weeks. Relative to pretreatment levels, the ex vivo HCV-specific CD8+ T-cell frequency decreased at 12 weeks after the end of treatment, along with a decreased antigen-experienced CD8(+) T-cell population. DAA treatment increased the proliferative capacity of HCV-specific CD8(+) T cells, but this change was not correlated with ex vivo function. Patients experiencing viral breakthrough or relapse exhibited defective restoration of T-cell function. Conclusion. Our present results indicated that DAA-mediated viral clearance only transiently restored ex vivo T-cell function, suggesting a need to enhance T-cell function in DAA-treated patients.