Direct-acting Antiviral-induced Transient Recovery of NK Cells in Early-stage Treatment of Chronic Hepatitis C Patients

Background and Aims:The rapid clearance of hepatitis C virus induced by direct-acting antivirals(DAAs)affects natural killer(NK)cells,but the reported results are not consistent,and the relative mechanism was unclear.This study focused on the dynamic changes of NK cells during and after DAA treatment and analyzed the reasons.Meth-ods:Peripheral blood from 35 chronic hepatitis C patients who were treated with DAAs were collected at baseline and weeks 1,2,4,12,and post-treatment week-12.The fre-quency,subset,and phenotype of NK cells were assayed by flow cytometry.Lactate dehydrogenase assays were used to evaluate the cytotoxicity of NK cells.Cytokine concentra-tions were measured with Luminex kits.Results:All pa-tients achieved a sustained viral response(SVR),and the NK cell frequencies were not changed significantly during DAA therapy.However,the cytotoxicity of NK cells recov-ered significantly early in week 1,and then continuously decreased below normal levels.The changes of genotypes including NKp30+,NKp46+,and NKG2A+NK cells were par-allel to NK function.The subset of CD56dim NK cells con-tinuously increased and did not return to normal even at 12 weeks after treatment.Interleukin(IL)-2,IL10,IL15,interferon-gamma,and tumor necrosis factor-alpha all in-creased after week 4,peaked at the end of therapy,and then exhibited varying degrees of reduction with time.Con-clusions:DAA treatment led to transient functional recov-ery of NK cells in the early stage of treatment,and then continuously decreased to below normal levels.Alterations of NK subsets,phenotypes,and the microenvironment may be involved in the changes.