Successful direct-acting antiviral therapy improves circulating mucosal-associated invariant T cells in patients with chronic HCV infection

OBJECTIVES: Mucosal-associated invariant T (MAIT) cells have been shown to contribute in the pathogenesis of various liver diseases, including chronic hepatitis C virus (HCV) infection. This study was aimed at investigating the frequency, phenotype, and function of circulating MAIT cells, as well as their alterations after successful direct-acting antivirals (DAAs) in HCV-infected patients with or without HIV infection. METHODS: A total 85 patients (51 HCV-monoinfection and 34 HCV/HIV-coinfection), who received elbasvir/grazoprevir from a clinical trial and 20 healthy controls were included. MAIT cells in blood were characterized using flow cytometry at baseline and 24 weeks post-treatment. RESULTS: HCV-monoinfected and HCV/HIV-coinfected patients achieved similar sustained virological response rates (SVR24, 94.1% vs. 97.1%). Circulating MAIT cells in the monoinfection and coinfection groups were presented at low frequencies in comparison with healthy controls (median, 1.1% vs. 1.1% vs. 2.4%, P<0.001) and exhibited features of chronic activation and impaired functional capacity. A negative correlation between circulating MAIT cell frequency and liver stiffness assessed by magnetic resonance elastography was observed. Compared with baseline, increased in circulating MAIT cells after successful DAA therapy was mainly detected in HCV-monoinfected patients compared with HCV/HIV-coinfected individuals. Moreover, MAIT cell restoration was predominantly observed among patients with significant fibrosis to cirrhosis (F2-F4). CONCLUSIONS: These data indicated that dysregulation of MAIT cells might play a role in the progression of chronic HCV infection. Partial restoration of MAIT cell frequency and function was observed after successful DAA therapy, particularly in HCV-monoinfected patients.