HCV‐Specific T‐Cell Recovery After a Year of SVR Following DAA Therapy

ABSTRACT Direct‐acting antiviral (DAA) drugs lead to sustained virologic response (SVR) in almost all treated patients with chronic hepatitis C virus (HCV) infection. Despite this success, the long‐term effects of HCV clearance by DAA therapy on T‐cell‐mediated antiviral immunity remain unclear, particularly concerning the restoration of immune function and its role in providing subsequent protection against reinfection. Our results demonstrated enhanced HCV‐specific cytokine production by CD4 + T cells in vitro, particularly in the activated CD38 + and CD38 + HLADR + subsets 1 year after DAA‐mediated cure with increased frequencies of TNF‐α + , IFNγ + TNF‐α + , IL‐2 + , and IL‐21 + cells. Notably, these subsets also exhibited reduced expressions of inhibitory markers, PD1 and TIGIT. Furthermore, reduced mitochondrial reactive oxygen species production and increased mitochondrial membrane potential were observed in CD38 + T helper cells, suggesting improved mitochondrial function. Significant reductions in serum IP‐10, MIP‐1β, and TNF‐α levels were observed, indicating decreased systemic inflammation. These findings suggest that DAA‐mediated HCV cure partially restores T helper cell function through reduced expression of inhibitory markers and improved mitochondrial activity in a subset of chronic HCV patients 1 year after SVR, which may potentially enhance immune protection and reduce the risk of reinfection.