联合使用甘草酸制剂对抗结核药物引起的药物性肝损伤的影响  

Effect of glycyrrhizic acid preparations on the liver injury induced by antituberculous drugs

作　　者：刘立 赵雁红 李国忠 常丽仙 马智慧 王戈 刘春云 沈凌筠 LIU Li;ZHAO Yanhong;LI Guozhong;CHANG Lixian;MA Zhihui;WANG Ge;LIU Chunyun;SHEN Lingyun(Department of Infectious Diseases,Yunnan Infectious Disease Clinical Medical Center,the Third People’s Hospital of Kunming,Kunming 650041,China)

机构地区：[1]昆明市第三人民医院云南省传染性疾病临床医学中心感染科,昆明650041

出　　处：《中国感染与化疗杂志》2023年第6期702-708,共7页Chinese Journal of Infection and Chemotherapy

基　　金：昆明市卫健委卫生科研项目(2020-3-10-112)。

摘　　要：目的 探讨联合使用甘草酸制剂对抗结核药物导致的药物性肝损害(DILI)的影响。方法 回顾性收集2020年1月—2021年6月208例肺结核患者,观察组105例使用2HRZE/4HR(H:异烟肼,R:利福平,Z:吡嗪酰胺,E:乙胺丁醇)加甘草酸制剂,甘草酸制剂累积剂量≥90累积日剂量(cDDD)。对照组103例使用2HRZE/4HR。采用Kaplan-Meier法比较两组DILI的累积发生率,以Cox比例风险回归模型分析肺结核患者发生DILI的风险及协同因素。结果 208例肺结核患者33例(15.9%)发生DILI,观察组105例和对照组103例分别有10例和23例发生DILI,观察组DILI累积发生率明显低于对照组(P=0.009),相对危险度为2.605(95%CI:1.240~5.475)。调整年龄、性别、白蛋白、肝肾功能等因素后,乙肝表面抗原(HBsAg)阳性(HR=12.850,95%CI:3.778~43.704)、CD4细胞(HR=0.998,95%CI:0.995~1.000)、肺外结核(HR=20.212,95%CI:2.491~163.977)是DILI发生的独立危险因素,差异均具有统计学意义(P<0.05),甘草酸制剂累积剂量治疗(HR=0.400,95%CI:0.186~0.860)是DILI发生的独立保护因素。结论 甘草酸制剂累积剂量治疗能显著降低肺结核患者肝损伤,保证抗结核治疗完成整个疗程,从而提高结核病的治愈率。Objective To explore the effect of glycyrrhizic acid preparations on the drug-induced liver injury(DILI)caused by anti-tuberculosis drugs.Methods The clinical data of 208 patients with pulmonary tuberculosis treated from January 2020 to June 2021 were retrospectively reviewed and analyzed.Overall,105 patients were treated with 2HRZE/4HR regimen(isoniazid,rifampicin,ethambutol and pyrazinamide daily for 2 months,followed by 4 months of isoniazid and rifampicin)plus glycyrrhizic acid preparations≥90 cumulative defined daily dose(cDDD),while 103 patients were treated with 2HRZE/4HR regimen without glycyrrhizic acid preparations.Kaplan-Meier method was used to compare the cumulative incidence of DILI between the two groups of patients.Cox proportional hazards regression model was used to analyze the risk factors and covariates of DILI in patients with pulmonary tuberculosis.Results DILI was identified in 33(15.9%)of the 208 patients with pulmonary tuberculosis,specifically in 9.5%(10/105)of the patients receiving glycyrrhizic acid preparations and in 22.3%(23/103)of the patients not receiving glycyrrhizic acid preparations(P=0.009).The relative risk was 2.605(95%CI:1.240,5.475)in the patients without glycyrrhizic acid preparations.After adjusting for age,sex,albumin,liver and kidney function and other factors,HBsAg positive(HR=12.850,95%CI:3.778,43.704),CD4(HR=0.998,95%CI:0.995,1.000),extrapulmonary tuberculosis(HR=20.212,95%CI:2.491,163.977)were independent risk factors for DILI(all P<0.05).Glycyrrhizic acid preparations≥90 cDDD(HR=0.400,95%CI:0.186,0.860)was an independent protective factor for DILI.Conclusions Glycyrrhizic acid preparations≥90 cDDD could significantly reduce the incidence of DILI in patients with pulmonary tuberculosis,and improve the cure rate of tuberculosis by enhancing patients’adherence to anti-tuberculosis treatment.

关 键 词：肺结核 药物性肝损伤 甘草酸制剂 累积剂量 抗结核治疗 

分 类 号：R978.3[医药卫生—药品]