结核病初治患者药物性肝损伤危险因素的分析

Risk factors for anti-tuberculosis drug-induced liver injury in treatment-naive tuberculosis patients

目的探讨结核病初治患者发生抗结核药物性肝损伤(anti-tuberculosis drug-induced liver injury, ATB-DILI)的危险因素, 为初次抗结核治疗的患者避免药物性肝损伤的发生提供依据。方法采用回顾性病例对照研究, 纳入河北医科大学第三医院2014年1月至2019年12月收治的结核病初治患者177例, 根据患者抗结核治疗期间是否发生ATB-DILI分为非ATB-DILI组和ATB-DILI组。收集两组患者进行抗结核治疗前性别、年龄、体重指数等一般情况, 肝脏生物化学指标、凝血酶原时间、血清铁蛋白水平, 基础肝脏情况及一线肝毒性抗结核药物应用种类等资料。统计学分析采用曼-惠特尼U检验和χ2检验, 采用多因素logistic回归分析结核病初治患者发生ATB-DILI的相关危险因素。结果 177例结核病初治患者的ATB-DILI发病率为20.3%(36/177)。非ATB-DILI组和ATB-DILI组丙氨酸转氨酶(alanine aminotransferase, ALT)、天冬氨酸转氨酶、高血清铁蛋白发生率、一线肝毒性抗结核药物应用种类的差异均有统计学意义(Z=-2.13, Z=-2.08,χ2=9.08, Z=-2.79, 均P<0.050)。多因素logistic回归分析显示, 慢性病毒性肝病[比值比(odds ratio, OR)=9.675, P<0.001]、一线肝毒性抗结核药物种类(OR=4.863, P=0.001)、ALT基线水平(OR=1.016, P=0.011)和高血清铁蛋白(OR=3.336, P=0.018)是ATB-DILI发生的独立危险因素。一线肝毒性抗结核药物应用种类(回归系数为1.582)、ALT基线水平(回归系数为0.016)与ATB-DILI的发生呈正相关。结论慢性病毒性肝病、一线肝毒性抗结核药物应用种类、ALT基线水平、高血清铁蛋白是ATB-DILI的独立危险因素。

Objective To investigate the risk factors for anti-tuberculosis drug-induced liver injury(ATB-DILI)in treatment-naive tuberculosis patients,and to provide evidence to avoid the occurrence of ATB-DILI in treatment-naive tuberculosis patients receiving anti-tuberculosis drug treatment.Methods A retrospective case-control study was carried out in 177 treatment-naive tuberculosis patients admitted to the Third Hospital of Hebei Medical University from January 2014 to December 2019.According to whether developed ATB-DILI during anti-tuberculosis treatment,the patients were divided into non-ATB-DILI group and ATB-DILI group.General basic data of sex,age and body mass index,hepatic biological parameters,prothrombin time,serum ferritin level,basic liver condition and the number of first line hepatotoxic anti-tuberculosis drugs were collected.Mann-Whitney U test and chi-square test were used for statistical analysis,and multi-factor logistic regression analysis was adopted to analyze risk factors for ATB-DILI in treatment-naive tuberculosis patients.Results The incidence of ATB-DILI was 20.3%(36/177)in the 177 treatment-naive tuberculosis patients.Alanine aminotransferase(ALT),aspartate aminotransferase,incidence of high serum ferritin and the number of first line hepatotoxic anti-tuberculosis drugs were significantly different between non-ATB-DILI group and ATB-DILI group(Z=-2.13,Z=-2.08,χ2=9.08 and Z=-2.79,respectively,all P<0.050).Multivariate logistic regression analysis showed that chronic viral liver disease(odds ratio(OR)=9.675,P<0.001),the number of first line hepatotoxic anti-tuberculosis drugs(OR=4.863,P=0.001),baseline ALT level(OR=1.016,P=0.011)and high serum ferritin level(OR=3.336,P=0.018)were the independent risk factors for ATB-DILI.The number of first line hepatotoxic anti-tuberculosis drugs(regression coefficient was 1.582)and baseline ALT level(regression coefficient was 0.016)were both positively correlated with the occurrence of ATB-DILI.Conclusions Chronic viral liver disease,the number of first line hepatotoxic anti-tuberculosis drugs,higher baseline ALT level and high serum ferritin level are the independent risk factors for ATB-DILI.