抗结核药物所致肝损伤患者血浆MiRNA-4284水平及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2019.02.015

实用肝脏病杂志 ›› 2019, Vol. 22 ›› Issue (2): 212-215.doi: 10.3969/j.issn.1672-5069.2019.02.015

抗结核药物所致肝损伤患者血浆MiRNA-4284水平及其临床意义探讨^*

吴秀欣,张惠勇,张凯

363000 福建省漳州市厦门大学附属东南医院内科（吴秀欣）;
肝病中心(张惠勇);
呼吸结核科(张凯)

收稿日期:2018-07-19 出版日期:2019-03-10 发布日期:2019-03-19
通讯作者: 张凯,E-mail:zk1126660319@163.com
作者简介:吴秀欣,女,29岁,大学本科,医师。E-mail:1510L1583@163.com
基金资助:
*福建省自然科学基金资助项目（编号：856975）

Changes of plasma microRNA-4284 in patients with anti-tuberculosis drug-induced hepatotoxicity

Wu Xiuxin, Zhang Huiyong, Zhang Kai

Department of Internal Medicine,Affiliated Southeast Hospital,Xiamen University,Zhangzhou 363000,Fujian Province,China

Received:2018-07-19 Online:2019-03-10 Published:2019-03-19

摘要/Abstract

摘要： 目的探讨抗结核药物导致的肝损伤（ATDH）患者血浆微小RNA(miRNA）-4284水平变化及其临床意义。方法在初治的200例肺结核患者,采用 WHO 推荐的标准6个月短程化学方案抗结核治疗,采用高通量实时荧光定量PCR技术检测血浆miRNA-4284水平。绘制血浆miRNA-4284水平诊断ATDH的ROC曲线,评估其诊断ATDH的效能。结果经过6个月抗结核治疗后,发生肝功能损伤70例（35.0%）,其中肝细胞型24例,胆汁淤积型20例,混合型26例;ATDH组血浆miRNA-4284水平为（1.9±1.6）,显著高于非ATDH组的【（0.9±0.6）,P< 0.05】;以血浆miRNA-4284水平=1.15为诊断ATDH的最佳截断点,其曲线下面积为0.71（95%CI：0.43~1.45）,诊断ATDH的敏感度为70.0%,特异度为69.9%,阳性预测值为77.8%,阴性预测值为67.4%,正确性为68.0%;经护肝治疗3个月,70例ATDH患者血清肝功能指标恢复至正常水平,而血浆miRNA-4284水平也降至（0.8±0.5）。结论 ATDH患者血浆miRNA-4284水平显著升高,在诊断ATDH和评估抗痨疗效方面具有一定的临床指导意义。

关键词: 药物性肝损伤, 抗结核药物性肝损伤, 微小RNA, 诊断效能

Abstract: Objective To investigate the changes of plasma microRNA（miRNA） -4284 in patients with anti-tuberculosis drug-induced hepatotoxicity（ATDH）. Methods A total of 200 naive patients pulmonary tuberculosis were recruited in this study,and all the patients received standardized WHO-recommended anti-tuberculosis therapy. High throughput real-time fluorescence quantitative PCR was applied to assay plasma miRNA-4284 levels. The ROC curve was drawn to evaluate the efficacy of plasma miRNA-4284 for diagnosis of ATDH. Results At the end of six month anti-tuberculosis,ATDH occurred in 70 cases（35.0%）,and out of them,the hepatocyte injuries in 24,cholestasis in 20,and mixed injuries in 26;plasma miRNA-4284 level in patients with ATDH was （1.9 ±1.6）,significantly higher than 【（0.9±0.6）,P<0.05】 in patients without;the sensitivity was 70.0%,the specificity was 69.9%,the positive predictive value was 77.8%,the negative predictive value was 67.4% and the accuracy was 68.0% when plasma miRNA-4284 level equal to 1.15 acted as the cut-off-value with the AUC being 0.71 （95%CI：0.43-1.45）;after three-month hepatoprotective therapy,serum liver function index in all the patients with ATDH recovered and their plasma miRNA-4284 levels also decreased to（0.8±0.5）. Conclusion Plasma miRNA-4284 level in patients with ATDH significantly increases,which might be helpful in the diagnosis and evaluation of anti-tuberculosis efficacy in clinical practice.

Key words: Drug-induced liver injury, Anti-tuberculosis drug-induced hepatotoxicity, MicroRNA, Diagnosis

吴秀欣,张惠勇,张凯. 抗结核药物所致肝损伤患者血浆MiRNA-4284水平及其临床意义探讨^*[J]. 实用肝脏病杂志, 2019, 22(2): 212-215.

Wu Xiuxin, Zhang Huiyong, Zhang Kai. Changes of plasma microRNA-4284 in patients with anti-tuberculosis drug-induced hepatotoxicity[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(2): 212-215.

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抗结核药物所致肝损伤患者血浆MiRNA-4284水平及其临床意义探讨^*

Changes of plasma microRNA-4284 in patients with anti-tuberculosis drug-induced hepatotoxicity

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