直接抗病毒药物治愈的慢性丙型肝炎患者NK细胞的免疫学特点分析  

Analysis of immunological characteristics of natural killer cells in cured chronic hepatitis C patients receiving direct-acting antivirals

作　　者：周文靖 史继静 李元元 王福生 ZHOU Wen-jing;SHI Ji-jing;LI Yuan-yuan;WANG Fu-sheng(Department of Basic Medical Sciences,Bengbu Medical College,233000,China)

机构地区：[1]蚌埠医学院基础医学院,233000 [2]郑州市第一人民医院中心实验室,450004 [3]中国人民解放军总医院第五医学中心感染病诊疗与研究中心,北京100039

出　　处：《传染病信息》2019年第1期37-41,共5页Infectious Disease Information

基　　金：河南省2018年科技发展计划项目(182102310594);国家自然科学基金(81601731)

摘　　要：目的探讨直接抗病毒药物(direct-acting antivirals, DAAs)治愈的慢性丙型肝炎(chronic hepatitis C, CHC)患者NK细胞的免疫学变化。方法入组13例经达拉他韦(daclatasvir, DCV)和阿舒瑞韦(asunaprevir, ASV)治疗24周的初治型HCV 1b型CHC患者,同时入组13例健康者为健康对照(healthy controls, HC)组。采用流式细胞术分析患者治疗前,治疗第24周,治疗结束后随访第12周、24周的外周血NK细胞表型和功能特点。结果 13例CHC患者经DCV/ASV抗病毒治疗均获得持续病毒学应答即临床治愈;与HC组相比,CHC患者抗病毒治疗前外周血NK细胞表达HLA-DR、NKP46、CD38的水平显著增高(P均<0.05),分泌CD107a和TNF-α的水平增高(P均<0.05),但产生IFN-γ的能力降低(P <0.05)。抗病毒治疗后,CHC患者外周血NK细胞活化程度降低,分泌IFN-γ的能力明显增强(P均<0.05)。结论经DAAs治愈的CHC患者外周血NK细胞的表型和功能显著改善。Objective To investigate the immunological characteristics of NK cells in patients with chronic hepatitis C(CHC)who were cured with direct-acting antivirals(DAAs)therapy.Methods Thirteen treatment-naive CHC patients of HCV 1b were enrolled and treated with daclatasvir/asunaprevir(DCV/ASV)for 24 weeks,meanwhile 13 healthy controls were recruited as healthy controls group.The phenotype and function of NK cells in all subjects 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.Results All of 13 CHC patients achieved sustained virological response after 24-week treatment of DCV/ASV,indicating a clinical cure.Compared with healthy controls,the expression levels of HLADR,NKP46 and CD38 in peripheral blood of CHC patients were significantly up-regulated before treatment(P<0.05),the secretion of CD107a and TNF-αwas increased(P<0.05),but the IFN-γproduction was decreased(P<0.05).After DCV/ASV treatment,the activation level of NK cells in peripheral blood of CHC patients was decreased,and IFN-γproduction was obviously improved(P<0.05).Conclusions In CHC patients cured with DAAs treatment,the phenotype and function of NK cells in peripheral blood are significantly improved.

关 键 词：丙型肝炎病毒 慢性丙型肝炎 自然杀伤细胞 直接抗病毒药物 

分 类 号：R512.63[医药卫生—内科学]