抗结核药物所致肝损伤的不良反应分析及风险因素研究

目的探究抗结核药物(ATD)引发药物性肝损伤(DILI)的临床特征和危险因素,建立风险预测模型。方法以60例抗结核药物所致DILI的患者为观察组,以同期行相同方案治疗的结核病患者1100例作为对照组,采用回顾性分析手段对两组患者的一般资料、临床表现、实验室指标等数据,进行对比分析,找出ATD引起DILI的独立危险因素并利用R软件建立列线图风险预测模型。结果60例ATD引起DILI的不良反应报告中以女性为主,占58.33%;平均年龄为46.83±11.24岁,其中40~69岁发生率最高,占56.67%;临床分型中包括40例肝细胞损伤型,13例胆汁淤积型,7例混合型;临床表现以食欲下降、乏力最为显著。风险因素分析中,年龄、基础肝病、糖尿病、胆囊疾病、ALB、TBIL、含吡嗪酰胺、合用其他增加肝毒性药物为TB患者DILI的独立危险因素。R软件建立的列线图预测模型C-index指数高达0.902,说明本模型具有较好的预测能力。结论运用列线图模型评分预测发生DILI的风险,对结核病患者个体化化疗方案制定具有重要指导意义。

Analysis of adverse reactions and risk factors of liver injury caused by anti-tuberculosis drugs

Objective Explore the clinical features and risk factors of drug-induced liver injury(DILI)caused by anti-tuberculosis drugs(ATD),and establish a risk prediction model.Methods 60 patients with DILI caused by anti-tuberculosis drugs were selected as the observation group,and 1100 patients with tuberculosis who received the same regimen during the same period were used as the control group.A retrospective analysis method was adopted to compare and analyze the general data,clinical performance,laboratory indicators,and other data of the two groups of patients,and to find out the independent risk factors of DILI caused by ATD and use R software to establish a nomogram risk prediction model.Results Of the 60 patients with ATD-induced DILI adverse reaction reports,females predominated(58.33%)and the average age was 46.83±11.24 years,with the majority in the 40-69 age group(56.67%).The clinical classification included 40 cases of hepatocellular injury type,13 cases of cholestasis type,and 7 cases of mixed type.The most significant clinical manifestations were decreased appetite and fatigue.In the analysis of risk factors,age,basic liver disease,diabetes,gallbladder disease,ALB,TBIL,containing pyrazine Amide,and combined with other drugs that increase hepatotoxicity were independent risk factors for DILI in TB patients.The C-index of the nomogram for predicting survival established by R software was 0.902,indicating that the model has a good predictive ability.Conclusion The use of nomogram model scores to predict the risk of DILI has important guiding significance for the formulation of individualized chemotherapy regimens for tuberculosis patients.