摘要
目的分析不同抗结核治疗方案致药物性肝损伤(DILI)情况及其与肝脏药物转运体1B1(SLCO1B1)/多药耐药性蛋白1(ABCB1)基因多态性的关联性。方法回顾性分析2018年10月-2020年4月医院收治的621例接受抗结核治疗的肺结核患者临床资料,按是否发生DILI分为DILI组78例、非DILI组543例,测定两组抗结核治疗前后肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、总胆红素(TBIL)]变化,分析两组的临床资料并筛选DILI的危险因素,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测SLCO1B1基因rs4149014位点及ABCB1基因rs2231142位点多态性,分析SLCO1B1/ABCB1基因多态性与DILI的相关性。结果78例出现DILI,发生率为12.56%(78/621),复治肺结核、耐多药肺结核患者DILI发生率高于初治肺结核患者,耐多药肺结核患者DILI发生率高于复治肺结核患者(P<0.05);78例DILI组抗结核治疗后ALT、AST、GGT、ALP、TBIL峰值均高于抗结核治疗前及非DILI组(P<0.01),非DILI组治疗前后ALT、AST、GGT、ALP、TBIL差异无统计学意义;年龄、肝病史、饮酒史、抗结核治疗时机为发生DILI的独立危险因素(P<0.05);DILI组SLCO1B1基因rs4149014位点的基因型TT、GT、等位基因T频率高于非DILI组,DILI组ABCB1基因rs2231142位点的基因型AC、等位基因A频率高于非DILI组(P<0.05);Logistic回归分析显示,SLCO1B1基因rs4149014位点的基因型GT、等位基因T及ABCB1基因rs2231142位点的基因型AC与肺结核患者DILI具有相关性(P<0.05)。结论抗结核药物治疗肺结核导致的DILI发生率高,SLCO1B1/ABCB1基因多态性也与DILI有密切关系,可能是DILI的易感基因。
OBJECTIVE To analyze the status of drug-induced liver injuries(DILI)caused by different antituberculosis treatments and its association with liver-specific solute carrier organic anion transporter family member 1B1(SLCO1B1)/ATP-bingding cassette subfamily B member 1(ABCB1)gene polymorphisms.METHODS The clinical data of 621patients with pulmonary tuberculosis who had underwent anti-tuberculosis treatments in the hospital between Oct.2018and Apr.2020were retrospectively analyzed,and the patients were divided into 78cases in DILI group and 543cases in non-DILI group according to whether DILI occured.Changes in liver function[alanine aminotransferase(ALT),aspartate aminotransferase(AST),glutamyl transpeptidase(GGT),alkaline phosphatase(ALP)and total bilirubin(TBIL)]of the two groups before and after anti-tuberculosis treatment were deter-mined,the clinical data of two groups were analyzed,and the risk factors of DILI were screened.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique was used to detect the rs4149014locus of SLCO1B1gene and the rs2231142locus of ABCB1gene,and the correlation between SLCO1B1/ABCB1gene polymorphisms and DILI was analyzed.RESULTS DILI occurred in 78cases with an incidence rate of 12.56%(78/621).The incidence of DILI in patients with retreated tuberculosis and multidrug-resistance tuberculosis was higher than that of newly treated tuberculosis patients,and the incidence of DILI in patients with multidrug-resistant tuberculosis was higher than that of retreated tuberculosis patients(P<0.05).The peak values of ALT,AST,GGT,ALP and TBIL after anti-tuberculosis treatment in 78cases of DILI group were higher than those before anti-tuberculosis treatment and the non-DILI group(P<0.01).There was no statistically significant difference in ALT,AST,GGT,ALP,and TBIL in the non-DILI group before and after treatment.Age,liver disease history,drinking history and timing of antituberculosis treatment were independent risk factors for DILI(P<0.05).The frequencies of genotyp
作者
王鲜茹
胡新俊
王雪茹
耿晓平
丁雅芳
WANG Xian-ru;HU Xin-jun;WANG Xue-ru;GENG Xiao-ping;DING Ya-fang(The First Affiliated New Area Hospital of Henan University of Science and Technology,Luoyang,Henan 471000,China;不详)
出处
《中华医院感染学杂志》
CAS
CSCD
北大核心
2021年第19期2920-2924,共5页
Chinese Journal of Nosocomiology
基金
国家自然科学基金资助项目(81600512)。
关键词
抗结核
治疗方案
药物性肝损伤
有机阴离子转运体1B1
多药耐药性蛋白1
基因多态性
关联性
Anti-tuberculosis
Therapeutic regimen
Drug-induced liver injuries
Solute carrier organic anion transporter family member 1B1
ATP-bingding cassette subfamily B menber 1
Gene polymorphism
Association
