77例耐多药肺结核患者采用含贝达喹啉方案治疗后肝损伤和QTc延长的临床分析

Clinical analysis of liver injury and QTc prolongation in 77 patients with multidrug-resistant tuberculosis treated with bedaquiline containing regimen

目的通过分析含贝达喹啉方案对西南地区耐多药结核患者肝损伤和QTc间期的临床特征,探讨其发病的危险因素。方法我院纳入的符合条件的耐多药结核患者,给予含贝达喹啉的治疗方案,检测生化指标和QTc值。结果完成治疗的77例患者中,出现肝损伤患者37例(48.1%),其中肝功能异常33例(42.9%),轻度肝损伤患者4例(5.2%)。38例(49.4%)发生QTc间期延长,其中450 ms≤QTc<500 ms患者30例(39.0%),QTc≥500 ms患者4例(5.2%),QTc≥60 ms患者28例(36.4%)。32~45岁和≥46岁的患者发生肝损伤的风险分别是18~31岁患者的3.11倍和7.90倍;合并肝炎患者发生肝损伤的风险是未合并肝炎患者的9.12倍。≥46岁的患者QTc间期延长发生风险是18~31岁患者的4.45倍;联合QTc延长的药物的患者QTc延长发生风险是未联合该类药物的4.10倍。结论含贝达喹啉方案引起的肝功能异常和QTc间期延长的比例较高,但是所有患者没有因为肝功能异常而停止使用贝达喹啉。年龄、合并肝炎是肝损伤发生的危险因素;年龄、联合QTc延长的药物是QTc延长发生的危险因素。在临床中,应密切关注具有以上高危因素患者的肝功能和心电图,及时采取措施,减少患者痛苦。

Objective To explore the risk factors of patients with multidrug-resistant tuberculosis in southwest of China,by analyzing the clinical characteristics of bedaquiline combining regimen on liver injury and QTc interval.Methods Eligible patients with multidrug-resistant tuberculosis were enrolled in our hospital,and provided with bedaquiline containing regimen.The values of biochemical indexes and QTc were monitored.Results Of the 77 patients,37 patients(37/77,48.1%)had liver injury,including 33 patients had hepatic function disorder and 4 patients had slight liver injury.38 patients(38/77,49.4%)had QTc interval prolongation,including 33 patients(39.0%)with 450 ms≤QTc<500 ms,4 patients(5.2%)with QTc≥500 ms and 28 patients(36.4%)with QTc≥60 ms.The risk of liver injury was 3.11 times and 7.90 times higher in patients with 32-45 years and≥46 years than 18-31 years,and patients with hepatitis was 9.12 times than that in patients without hepatitis.The risk of QTc interval prolongation was 4.45 times higher in patients with≥46 years than 18-31 years,and patients with QTc prolongation drugs was 4.10 times than that in patients without QTc prolongation drugs.Conclusion The regimen containing bedaquiline increases the occurrence of hepatic function disorder and QTc interval prolongation.However,all hepatic function disorder does not lead to bedaquiline discontinuation.Age and hepatitis are the risk factors of liver injury.Age and drugs combined with QTc prolongation are the risk factors of QTc prolongation.In clinic,we should pay close attention to the liver function and electrocardiogram of patients with the above risk factors,and take timely measures to reduce the pain of patients.