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基线血清外泌体miR-155-5p联合乙型肝炎病毒DNA定量实验预测聚乙二醇干扰素治疗乙型肝炎e抗原阳性慢性乙型肝炎的疗效
引用本文:胡乾坤,王倩倩,李强,黄晨璐,许伟,张毅,李新艳,陈良,黄玉仙.基线血清外泌体miR-155-5p联合乙型肝炎病毒DNA定量实验预测聚乙二醇干扰素治疗乙型肝炎e抗原阳性慢性乙型肝炎的疗效[J].微生物与感染,2020,15(6):385-392.
作者姓名:胡乾坤  王倩倩  李强  黄晨璐  许伟  张毅  李新艳  陈良  黄玉仙
作者单位:复旦大学附属公共卫生临床中心肝病科,上海 201508
基金项目:上海申康医院发展中心市级医院新兴前沿技术联合攻关项目(SHDC12017125),上海市科学技术委员会医学引导类科技项目(18411966500)
摘    要:探讨聚乙二醇干扰素(peginterferon, Peg-IFN)治疗乙型肝炎e抗原(hepatitis B e antigen, HBeAg)阳性慢性乙型肝炎(chronic hepatitis B, CHB)患者48周后,基线血清外泌体miR-155-5p表达水平联合乙型肝炎病毒DNA定量实验在预测HBeAg血清学转换中的价值。回顾性分析2016年6月至2019年6月在本中心初次接受抗病毒治疗的HBeAg阳性CHB患者88例。根据Peg-IFN治疗48周后是否发生HBeAg血清学转换,将患者分为治疗应答组和无应答组。采用多因素logistic回归探讨预测Peg-IFN治疗应答的因子,并应用受试者工作特征(receiver operating characteristic, ROC)曲线下面积评估预测效能。结果发现基线血清外泌体miR-155-5p(OR=2.193,95% CI 1.315~3.655,P=0.003)和HBV DNA(OR=0.398,95% CI 0.163~0.976,P=0.036)是Peg-IFN治疗效果的独立预测因子。基线血清外泌体miR-155-5p和HBV DNA的截断值分别取2.3和7.2 log10IU/mL时,相应的ROC曲线下面积分别为0.788(95% CI 0.682~0.893)和0.704(95% CI 0.577~0.824)。基线血清外泌体miR-155-5p表达水平≥2.3且HBV DNA定量≤7.2 log10IU/mL的患者,Peg-IFN治疗48周后其HBeAg血清学转换率最高,为66.67% (10/15);而基线血清外泌体miR-155-5p表达水平<2.3且HBV DNA定量>7.2 log10IU/mL的患者,Peg-IFN 治疗48周后其HBeAg血清学转换率最低,仅为3.03%(1/33)。这些结果表明,基线血清外泌体miR-155-5p表达水平联合HBV DNA定量实验可以作为Peg-IFN 治疗HBeAg阳性CHB疗效的预测因子,对于优化CHB的抗病毒治疗有积极作用。

关 键 词:乙型肝炎  慢性  外泌体  miR-155-5p  乙型肝炎病毒DNA  聚乙二醇干扰素  

Baseline serum exosomal miR-155-5p combined with HBV DNA can predict HBeAg seroconversion in chronic hepatitis B patients receiving peginterferon
HU Qiankun,WANG Qianqian,LI Qiang,HUANG Chenlu,XU Wei,ZHANG Yi,LI Xinyan,CHEN Liang,HUANG Yuxian.Baseline serum exosomal miR-155-5p combined with HBV DNA can predict HBeAg seroconversion in chronic hepatitis B patients receiving peginterferon[J].Journal of Microbes and Infection,2020,15(6):385-392.
Authors:HU Qiankun  WANG Qianqian  LI Qiang  HUANG Chenlu  XU Wei  ZHANG Yi  LI Xinyan  CHEN Liang  HUANG Yuxian
Institution:Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
Abstract:The aim of the present study was to explore the value of baseline serum exosomal miR-155-5p expression level combined with HBV DNA quantification in predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN) for 48 weeks. A total of 88 HBeAg-positive CHB patients who initially received Peg-IFN therapy in our hospital from June 2016 to June 2019 were retrospectively analyzed. Patients were divided into treatment response and non-response group according to HBeAg seroconversion after Peg-IFN treatment for 48 weeks. Multivariate logistic regression analysis was performed to identify predictors of treatment response, and the area under receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy. The results indicated that baseline serum exosomal miR-155-5p odds ratio (OR) =2.193, 95% confidence interval (CI) 1.315~3.655, P=0.003] and HBV DNA (OR=0.398, 95% CI 0.163~0.976, P=0.036) were independent predictors for HBeAg seroconversion. The optimal cut-off value of baseline serum exosomal miR-155-5p and HBV DNA were 2.3 and 7.2 log10IU/mL, respectively; and the corresponding area under ROC curves were 0.788 (95% CI 0.682~0.893) and 0.704 (95% CI 0.577~0.824), respectively. Patients with baseline serum exosomal miR-155-5p expression level ≥2.3 and HBV DNA ≤7.2 log10IU/mL had 66.67% (10/15) rates of HBeAg seroconversion, whereas the rates of HBeAg seroconversion among patients with unfavorable baseline characteristics were only 3.03% (1/33). Taken together, these results suggest that baseline serum exosomal miR-155-5p combined with HBV DNA quantification may serve as a useful predictor of Peg-IFN therapy efficacy in HBeAg-positive CHB patients.
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