Characteristic And Its Implication Of Natural Killer Cells In Chronic Hepatitis C Patients Cured With Direct-Acting Antiviral Agents

Background: Chronic hepatitis C(CHC)is an infectious disease caused by hepatitis C virus(HCV)infection,which seriously threatens human health.In recent years,the emergence of direct-acting antiviral agents(DAAs)has made HCV infection a curable disease.As a major component of the innate immune system,natural killer(NK)cells play an important role not only in the spontaneous elimination of the virus in the early stage of HCV infection,but also in the treatment of chronic infection.At present,most of the research on DAAs focuses on its clinical efficacy,and there are few studies on the effects of DAAs treatment on immune system.The effect of DAAs treatment on the immunological characteristics of peripheral blood NK cells in CHC patients remains unclear.Objective: This study investigated the subsets,phenotypes and functions of peripheral blood NK cells from treatment-naive HCV gentype-1b CHC patients who were treated with Daclatasvir and Asunaprevir(DCV/ASV)to explore the effect of DAAs on the immunological characteristics of NK cells in peripheral blood of CHC patients.Methods: Thirteen treatment-naive genotype 1b HCV infected patients were enrolled and treated with DCV/ASV for 24 weeks,meanwhile,13 age-and sex-matched uninfected subjects were recruited as healthy controls(HC).The subsets,phenotypes(HLA-DR,CD38,NKp46,NKp30,NKG2A)and cytokine production(CD107a,IFN-?,TNF-?)of peripheral blood NK cells in CHC patients were detected before treatment,at week 24 of therapy,week 12 and week 24 of follow-up after the end of therapy by flow cytometry and compared with those from 13 healthy controls.Results:(1)All of 13 CHC patients achieved sustained viral response after 24-week treatment of DCV/ASV,and their liver function returned to normal.(2)Compared with healthy controls,the distribution of NK cell-subsets in CHC patients was changed before treatment.The expression levels of HLA-DR,NKp46 and CD38 in peripheral blood of CHC patients were significantly up-regulated,the expression of CD107 a and the secretion of TNF-? was increased,but the IFN-? production was decreased.(3)In CHC patients cured with DAAs treatment,we observed that the change of peripheral blood NK cell-subsets was reversed,the expression levels of HLA-DR,NKp46 and CD38 on peripheral blood NK cells in CHC patients were significantly decreased,the expression of CD107 a was decreased,and the IFN-? production was obviously increased.Conclusion: DAAs can effectively eradicate HCV.In CHC patients cured with DAAs treatment,the activity of peripheral blood NK cells is decreased,the function and subsets of circulating NK cells are significantly restored.This study demonstrates that DAAs treatment can not only directly inhibit the replication of HCV,but also can improve the phenotype and function of NK cells in CHC patients.