非活动HBsAg携带者经聚乙二醇干扰素治疗获得HBsAg清除与Th1及Th2类细胞因子水平的相关性研究  

Association between serum levels of Th1 and Th2 cytokines and HBsAg clearance in inactive hepatitis S antigen carriers received Peg-interferon

作　　者：曹振环[1] 王俊丽[1] 吴芳芳[1] 郑燕红[1] 陈新月[1] CAO Zhen-huan;WANG Jun-li;WU Fang-fang;ZHENG Yan-hong;CHEN Xin-yue(Department of Liver Diseases,Beijing You＇an Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院肝病综合科,北京100069

出　　处：《中国病毒病杂志》2018年第4期303-308,共6页Chinese Journal of Viral Diseases

基　　金："十三五"国家科技重大专项课题(2017ZX10202201);首都临床特色应用研究项目(Z161100000516018;Z171100001017062);首都卫生发展科研专项项目(首发2016-1-2183;首发2018-2-2183);北京市医院管理局青年人才培养"青苗"计划项目(QML20161701);北京市教育委员会科技计划一般项目(11720674);首都医科大学基础与临床合作项目(17JL-07);首都医科大学重点实验室开放研究课题(2-03-02-BJYAH2016001);丰台区卫生计生系统科研项目(2016-57)

摘　　要：目的探讨聚乙二醇干扰素(pegylated interferon,Peg IFN)治疗非活动性HBsAg携带者(inactive hepatitis S antigen carries,IHC)发生HBsAg清除与辅助性T淋巴细胞(Th)1类细胞因子:白细胞介素(interleukin,IL)-2、干扰素(interferon,IFN)-γ、肿瘤坏死因子(tumor necrosis factor,TNF)-α,Th2类细胞因子:IL-10、IL-13水平的相关性。方法入组2012年1月~2016年1月就诊于首都医科大学附属北京佑安医院的24例IHC患者,全部患者为初治,未曾使用过抗病毒药物。给予Peg IFN治疗(Peg IFNα-2a135μg,皮下注射,1次/周)24周,获得HBsAg清除者(R组)17例,未获得清除者7例(NR组),同时纳入11例健康者(HC组)。用液相芯片技术检测健康者及IHC患者基线、治疗12周和24周血清IL-2、IFN-γ、TNF-α、IL-10、IL-13水平。结果 IHC的Th1类细胞因子(IL-2、IFN-γ、TNF-α)水平均低于健康者(P=0.033;P=0.003;P<0.001),而Th2类细胞因子(IL-10、IL-13)水平均高于健康者(P=0.001;P=0.001)。R组患者经Peg IFN治疗后,Th1类细胞因子IL-2、IFN-γ水平升高明显,之后24周有所下降:IL-2水平从(4.82±3.08)pg/ml升高至(12.46±5.33)pg/ml(P=0.021),之后下降至(3.43±2.44)pg/ml(P=0.007);IFN-γ基线水平(81.27±35.50)pg/ml,12周升高到(113.35±33.73)pg/ml(P=0.005),24周下降至(60.37±24.07)pg/ml(P<0.001)。NR组患者无此现象。R组患者Peg IFN治疗后,Th2类细胞因子IL-10水平明显下降(P=0.002),基线为(23.13±19.76)pg/ml,12周下降至(16.11±8.69)pg/ml,24周下降至(8.25±4.19)pg/ml。24周与基线相比,差异有统计学意义(P=0.002)。而NR组无此变化。R组与NR组患者IL-13水平均呈下降趋势,但差异均无统计学意义。结论 Peg IFN治疗IHC,Th1类细胞因子升高、Th2类细胞因子下降可能预示着HBsAg清除。Objective To study the correlation of HBsAg clearance with serum levels of Th1 and Th2 cytokines IL-2,IFN-γ,TNF-α,IL-10 and IL-13 in inactive hepatitis S antigen carriers（IHC）. Methods A total of24 IHC patients were admitted to Beijing You′an Hospital from January 2012 to January 2016.All patients were not treated with any other antiviral drugs before Peg IFN was given for 24 weeks.Eleven healthy controls were recruited in the study.Plasma cytokines（IL-2,IFN-γ,TNF-α,IL-10 and IL-13）were detected by Luminex technology at baseline,12 and 24 weeks. Results Of the 24 patients,17 achieved HBsAg clearance（group R）while 7 cases did not（group NR）.Comparing to controls,the levels of Th1 cytokines in IHCs were lower（IL-2：P=0.033,IFN-γ：P=0.003,TNF-α：P0.001）while Th2 cytokines were higher（IL-10：P=0.001,IL-13：P=0.001）.After antiviral treatment with Peg IFN,the levels of plasma IL-2 and IFN-γincreased significantly at week 12 and decreased significantly at week 24.IL-2 increased from（4.82±3.08）pg/ml to（12.46±5.33）pg/ml at week 12（P=0.021）,then decreased to（3.43±2.44）pg/ml at week 24（P=0.007）.IFN-γincreased from（81.27±35.50）pg/ml to（113.35±33.73）pg/ml（P=0.005）,then decreased to（60.37±24.07）pg/ml（P0.001）at week 24.There were no significant differences in patients of group NR.After treatment with Peg IFN,the level of plasma IL-10 decreased significantly from（23.13±19.76）pg/ml to（16.11±8.69）pg/ml at week 12,（8.25±4.19）pg/ml at week 24（P=0.002）in R group.The levels of plasma IL-13 decreased in both R and NR group but no statistical significance. Conclusions During the treatment of Peg IFN,the increasing levels of Th1 cytokines and decreasing levels of Th2 cytokines may benefit the HBsAg clearance in inactive hepatitis S antigen carriers.

关 键 词：非活动性HBSAG携带者 聚乙二醇干扰素 乙型肝炎病毒 TH1类细胞因子 TH2类细胞因子 HBsAg清除 

分 类 号：R512.62[医药卫生—内科学]