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*

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。

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

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.