The pathogenesis,diagnosis,and treatment of drug-induced liver injury with extrahepatic adverse drug reactions
-
摘要: 药物性肝损伤(DILI)合并肝外药物不良反应(EHADR)是指由导致肝损伤的同一药物所致的、与DILI同时或先后发生的肝外组织器官的损伤,例如皮肤、胃肠道、血液系统、心血管系统、骨关节系统等的损伤,是在关注DILI的同时也应加以重视的重要临床问题。DILI合并EHADR并不少见,其发病机制可能与药物的理化性质、分布、代谢、排泄、生物学活性、免疫学特性,以及宿主遗传背景及基础疾病等多方面的因素相关,其诊疗较单纯DILI更具有挑战性。Abstract: Drug-induced liver injury( DILI) with extrahepatic adverse drug reaction( EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI,such as the skin,gastrointestinal tract,blood system,cardiovascular system,and bone and joint system,and it should be taken seriously in clinical practice. DILI with EHADR is not rare,and its pathogenesis may be associated with various factors including the physicochemical properties,distribution,metabolism,excretion,biological activity,and immunological properties of drugs,host genetic background,and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone.
-
Key words:
- drug-induced liver injury /
- drug toxicity /
- drug hypersensitivity /
- pathologic processes /
- diagnosis /
- therapeutics
-
[1] Drug-induced Liver Disease Study Group,Chinese Society of Hepatology,Chinese Medical Association. Guidelines for the management of drug-induced liver injury[J]. J Clin Hepatol,2015,31(11):1752-1769.(in Chinese)中华医学会肝病学分会药物性肝病学组.药物性肝损伤诊治指南[J].临床肝胆病杂志,2015,31(11):1752-1769. [2] WANG DY,SALEM JE,COHEN JV,et al. Fatal toxic effects associated with immune checkpoint inhibitors:A systematic review and meta-analysis[J]. JAMA Oncol,2018,4(12):1721-1728. [3] DEVARBHAVI H,RAJ S,ARADYA VH,et al. Drug-induced liver injury associated with Stevens-Johnson syndrome/toxic epidermal necrolysis:Patient characteristics, causes, and outcome in 36 cases[J]. Hepatology,2016,63(3):993-999. [4] FANG WC,ADLER NR,GRAUDINS LV,et al. Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions:Experience from two Australian tertiary hospitals[J]. Intern Med J,2018,48(5):549-555. [5] KARDAUN SH,SEKULA P,VALEYRIE-ALLANORE L,et al.Drug reaction with eosinophilia and systemic symptoms(DRESS):An original multisystem adverse drug reaction. Results from the prospective RegiSCAR study[J]. Br J Dermatol,2013,169(5):1071-1080. [6] DONG S,HU S,CAI Q. Mechanism of fatal toxic effect associated with immune checkpoint inhibitors and its individualized management[J]. China Cancer,2019,28(6):440-444.(in Chinese)董爽,胡胜,蔡茜.免疫检查点致死性副作用的机制和个体化处理[J].中国肿瘤,2019,28(6):440-444. [7] POSTOW MA,SIDLOW R,HELLMANN MD. Immune-related adverse events associated with immune checkpoint blockade[J]. N Engl J Med,2018,378(2):158-168. [8] WALSH S,DIAZ-CANO S,HIGGINS E,et al. Drug reaction with eosinophilia and systemic symptoms:Is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases[J]. Br J Dermatol,2013,168(2):391-401. [9] IVERSEN MB,REINERT LS,THOMSEN MK,et al. An innate antiviral pathway acting before interferons at epithelial surfaces[J]. Nat Immunol,2016,17(2):150-158. [10] KIRKWOOD JM,BENDER C,AGARWALA S,et al. Mechanisms and management of toxicities associated with highdose interferon alfa-2b therapy[J]. J Clin Oncol,2002,20(17):3703-3718. [11] REKER D,BLUM SM,STEIGER C,et al.“Inactive”ingredients in oral medications[J]. Sci Transl Med,2019,11(483):eaau6753. [12] LIU M,YANG XZ,YU YC. Current status of the pathogenesis,diagnosis,and treatment of drug-induced cholestasis[J]. J Clin Hepatol,2019,35(2):252-256.(in Chinese)刘梦,杨玄子,于乐成.胆汁淤积型药物性肝损伤的发病机制及诊治[J].临床肝胆病杂志,2019,35(2):252-256. [13] YU YC,FAN Y,CHEN CW. Diagnosis and treatment of druginduced liver injury[J]. J Clin Hepatol,2018,34(6):1160-1165.(in Chinese)于乐成,范晔,陈成伟.药物性肝损伤的诊断和治疗[J].临床肝胆病杂志,2018,34(6):1160-1165. [14] ULLDEMOLINS M,ROBERTS JA,RELLO J,et al. The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically il patients[J]. Clin Pharmacokinet,2011,50(2):99-110. [15] LI XX,DU FY,LIU HX,et al. Investigation of the active components in Tripterygium wilfordii leading to its acute hepatotoxicty and nephrotoxicity[J]. J Ethnopharmacol,2015,162:238-243. [16] European Association for the Study of the Liver. EASL clinical practice guidelines:Drug-induced liver injury[J]. J Hepatol,2019,70(6):1222-1261.
本文二维码
计量
- 文章访问数: 1157
- HTML全文浏览量: 22
- PDF下载量: 372
- 被引次数: 0