Th1／Th2／Th17细胞因子在慢性乙型肝炎患者恩替卡韦停药后维持病毒学应答中的作用  

Role of Th1/Th2/Th17 cytokines in maintaining virological response after entecavir discontinuation in patients with chronic hepatitis B

作　　者：邱源旺 甘建和[2] 杨文龙[3] 戴亚萍 王俊[1] 张波[1] 汪铮 苏婷婷 李燚光 周红燕 徐微 黄利华 Qiu Yuanwang, Gan Jianhe, Yang Wenlong, Dai Yaping, Wang Jun, Zhang Bo, Wang Zhen, Su Tingting, Li Yiguang, Zhou Hongyan, Xu Wei, Huang Lihua(The Fifth People＇s Hospital of Wuxi, Wuxi 214005, China ; The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China ; The First Affiliated Hospital of Suzhou University, Suzhou 215006, China)

机构地区：[1]无锡市第五人民医院,214005 [2]苏州大学附属第一医院,215006 [3]南昌大学第二附属医院,330006

出　　处：《中华实验和临床病毒学杂志》2018年第1期43-47,共5页Chinese Journal of Experimental and Clinical Virology

基　　金：中国肝炎防治基金会天晴肝病研究基金（TQGB2011004）;南京医科大学科技发展基金重点项目（2012NJMU072）;无锡市科技发展基金（2014CSE31N1421）

摘　　要：目的 前瞻性研究HBeAg阳性慢性乙型肝炎（CHB）患者恩替卡韦停药后Th1/Th2/Th17细胞因子表达水平的变化特点,探讨其在恩替卡韦停药后维持病毒学应答中的作用.方法 入选接受恩替卡韦治疗且达到我国2010年发布的慢性乙型肝炎防治指南停药标准的CHB患者112例,根据停药52周复发情况分为病毒学持续应答组（SVR）和病毒学复发组（VR）,分别在停药0、12、24、52周检测血清Th1/Th2/Th17相关细胞因子水平,分析各细胞因子在SVR组和VR组的动态变化特点及其表达差异.结果 SVR组停药后Th1型细胞因子中IFN-γ水平稳定在较高水平,Th2类细胞因子IL-10水平呈显著下降趋势;SVR组患者在各随访时间点IFN-γ水平均显著高于VR组患者（t=2.983、3.916、5.964、4.515,均P＜0.05）.VR组患者停药后Th1细胞因子IFN-γ水平前24周呈下降趋势,24周后呈上升趋势,Th2类细胞因子稳定在较高水平.VR组患者在停药后各随访时间点IL-10水平均显著高于SVR组患者（t=-3.501、-3.663、-4.643、-5.896,均P＜0.05）.SVR组患者停药后各随访时间点IL-17A水平高于复发组,但组间结果比较差异均无统计学意义（t=0.514、0.899、0.501、0.950,均P＞0.05）.结论 Th1细胞因子IFN-γ水平稳定在较高水平表达有利于恩替卡韦停药后维持病毒学应答,Th2细胞因子IL-10水平的高表达可能与病毒学复发有关.Objective To explore the characteristics underlying Th1/Th2/Th17 expression level after entecavir （ETV） discontinuation of chronic hepatitis B （CHB） patients who were HBeAg-positive and define the role of Th1/Th2/Th17 in maintaining virological response after ETV discontinuation.Methods We selected 112 HBeAg positive CHB patients who met the withdrawal criteria according to the guideline of prevention and treatment of chronic hepatitis B （2010 version）,and we also separated them into virology sustained response （SVR） group and virological relapse （VR） group according to the recurrence in 52 weeks.We detected serum level of Th1/Th2/h17 related cytokines during 0,12,24 and 52 weeks follow-up to further analyze their dynamic changes and expression differences.Results The results of the study reveals that serum levels of IFN-γ in the group of SVR were at a higher level compared with VR group during follow-up （all P 〈 0.05）.While,the serum level of IL-10 decreased in SVR group and was lower than the paired IL-10 level in VR group with significance during follow-up.In VR group,the serum level of IFN-γ decreased during the first 24 weeks after ETV withdrawal,and after then,the level rose.The serum levels of IFN-γ （Th1） in SVR patients were significantly higher than those in VR patients in the different follow-up time points after ETV discontinuation （all P 〈 0.05）.And the serum levels of IL-10 （Th2） in SVR patients were significantly lower than that in VR patients （all P 〈 0.05）.The comparison of serum levels of IL-17A （Th17） between the two groups had no significant difference （all P 〉 0.005）.Conclusions The serum level of IFN-γ in SVR group maintained a high level is conducive to maintaining virological response after ETV withdrawal and high level of IL-10 may be related to virologic relapse.

关 键 词：细胞因子 肝炎 乙型 慢性 恩替卡韦 复发 

分 类 号：R512.62[医药卫生—内科学]