获得性免疫缺陷综合征患者应用复方磺胺甲噁唑致药物性肝损伤危险因素分析  

Risk factors analysis on drug-induced liver injury in acquired immunodeficiency syndrome patients treated with compound sulfamethoxazole

作　　者：邱新野[1] 尹月[2] 刘炜 QIU Xin-ye;YIN Yue;LIU Wei(Department of Pharmacy,Beijing Youan Hospital,Capital Medical University,BEIJING 100069,China;Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pharmacy,Peking University Cancer Hospital&Institute,BEIJING 100142,China)

机构地区：[1]首都医科大学附属北京佑安医院药学部,北京100069 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142

出　　处：《中国新药与临床杂志》2024年第9期686-690,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：首都医科大学附属北京佑安医院2021年度中青年人才孵育项目(YNKTGL2021002)。

摘　　要：目的研究复方磺胺甲噁唑(SMZ-TMP)致获得性免疫缺陷综合征(AIDS)患者药物性肝损伤(DILI)的危险因素,为临床药物警戒及合理用药提供参考。方法回顾性收集2020年12月至2022年12月在本院住院并服用SMZ-TMP治疗的AIDS患者的病例资料,将服用SMZ-TMP后发生DILI患者与未发生DILI患者的一般资料进行比较,并构建二分类logistic回归方程,筛选出AIDS患者应用SMZ-TMP致药物性肝损伤的危险因素。结果271例服用SMZ-TMP治疗的AIDS患者中,共有29例发生DILI,均为男性,其中27例为肝细胞损伤型,2例为胆汁淤积型,经对症治疗后全部患者临床症状均好转或痊愈。相关因素分析显示,患者合并过敏史(OR=15.334,95%CI:3.147~74.710)、未进行抗病毒治疗或使用替诺福韦+拉米夫定+洛匹那韦/利托那韦(TDF+3TC+LPV/r)方案(OR=56.123,95%CI:10.797~291.719)、SMZ-TMP日剂量≥12片(OR=52.809,95%CI:9.894~281.868)、丙氨酸转氨酶(ALT)≥23 U·L^(-1)(OR=18.514,95%CI:3.993~85.843)、CD4^(+)T淋巴细胞数≤110个·μL^(-1)(OR=40.586,95%CI:6.625~248.634)及CD8^(+)T淋巴细胞数≤920个·μL^(-1)(OR=135.978,95%CI:11.190~1652.303),均可增加AIDS患者SMZ-TMP相关DILI的发生风险(P<0.05)。结论AIDS患者SMZ-TMP相关DILI发生率较高,过敏史、抗病毒治疗方案的选择、SMZ-TMP剂量、ALT水平、CD4^(+)及CD8^(+)T淋巴细胞数为AIDS患者发生SMZTMP相关DILI的独立危险因素,应加强高风险人群监测,并及早采取干预措施。AIM To explore the risk factors of drug-induced liver injury(DILI)of compound sulfamethoxazole(sulfamethoxazole-trimethoprim,SMZ-TMP)in acquired immunodeficiency syndrome(AIDS)patients and provide reference for clinical pharmacovigilance and rational drug use.METHODS The data of AIDS patients treated with SMZ-TMP in our hospital from December 2020 to December 2022 were collected retrospectively.The general information of patients with DILI after taking SMZ-TMP was compared with that of patients without DILI,and binary logistic regression equation was constructed to screen out the risk factors of DILI in AIDS patients induced by SMZ-TMP.RESULTS Totally 271 AIDS patients were involved,and 29 patients had DILI,all of whom were male.Among them,27 patients were of hepatocellular injury pattern and 2 patients were of cholestatic injury pattern.All DILI patients were cured or improved after symptomatic treatment.Relevant factor analysis showed that,allergy history(OR=15.334,95%CI:3.147 to 74.710),no receiving antiviral treatment or tenofovir+lamivudine+lopinavir/ritonavir(TDF+3TC+LPV/r)regimen(OR=56.123,95%CI:10.797 to 291.719),daily dose of SMZ-TMP≥12 tablets(OR=52.809,95%CI:9.894 to 281.868),alanine transaminase(ALT)≥23 U·L^(-1)(OR=18.514,95%CI:3.993 to 85.843),CD4^(+)T cell≤110·μL^(-1)(OR=40.586,95%CI:6.625 to 248.634),and CD8^(+)T cell≤920·μL^(-1)(OR=135.978,95%CI:11.190 to 1652.303)can increase the risk of SMZ-TMP related DILI in AIDS patients(P<0.05).CONCLUSION The incidence of SMZ-TMP related DILI is relatively high in AIDS patients.Allergy history,selection of antiviral treatment regimens,dose of SMZ-TMP,ALT level,and CD4^(+)and CD8^(+)T lymphocyte counts are the independent risk factors for SMZ-TMP related DILI in AIDS patients.Monitoring of highrisk population should be strengthened and early intervention measures should be taken.

关 键 词：复方磺胺甲噁唑 获得性免疫缺陷综合征 药物性肝损伤 危险因素 

分 类 号：R512.91[医药卫生—内科学] R575.1[医药卫生—临床医学]