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药物性肝损伤的类型和表型
Drug-Induced Liver Injury — Types and Phenotypes


Jay H. Hoofnagle ... 其他 • 2019.07.18
相关阅读
• 癌症免疫治疗中药物性肝损伤的临床结局

NEJM综述阐明药物性肝损伤

 

肖小河

解放军总医院第五医学中心中西医结合诊疗与研究中心


药物性肝损伤(drug-induced liver injury,DILI)是指在药物使用过程中,由于药物及其代谢产物而引起的肝脏损伤,是最常见的药物严重不良反应之一。然而,由于DILI涉及药物品种众多,表型特征、损伤机制复杂,极大限制了人们对DILI的认识和理解,给临床诊疗和安全用药带来巨大挑战。

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药物性肝损伤在诊断和治疗方面是一个不常见但具有挑战性的临床问题1-3。其发病率估计为每10万人中14~19例,其中30%伴发黄疸4,5。药物性肝损伤占黄疸住院人数的3%~5%6,是大多数西方国家急性肝衰竭的最常见原因,占急性肝衰竭病例的一半以上7,8。在对于病毒性、自身免疫性和遗传性肝病的了解,以及在这些疾病的预防和治疗方面,我们已经取得进展,但在药物性肝损伤方面取得的进展并不大。

药物性肝损伤的诊断尤其具有挑战性,因为其诊断方法基本上是排除其他病因。药物性肝损伤的诊断主要涉及以下方面:所涉药物开始用药后肝损伤的发生时间(潜伏期)、停止用药后肝损伤消退(“去激发”)、再次暴露后复发(再激发)、对药物肝毒性潜力的了解(可能性)及临床表现(表型)9-11。除了极少数例外,药物性肝损伤并无特异性诊断标志物,而特殊检查(肝活检、影像学检查和血清学标志物检查)主要是有助于排除引起肝损伤的其他原因。可能引起肝损伤的大量药物突显了这些挑战。美国国立卫生研究院主办的肝毒性网站LiverTox描述了1,200多种药物(处方药和非处方药、草药制品、营养补充剂、金属和毒素),以及它们引起肝损伤的可能性12。在网站描述的971种处方药中,447种(46%)在至少一份已发表的病例报告中涉及肝损伤11。这篇简短的综述无法涵盖药物性肝损伤的各个方面,而是重点关注一般原则、新的概念和当前面临的挑战,有多处详细信息参考LiverTox网站。





作者信息

Jay H. Hoofnagle, M.D., and Einar S. Björnsson, M.D.
From the Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (J.H.H.); and the Department of Internal Medicine, National University Hospital of Iceland, and the Faculty of Medicine, University of Iceland — both in Reykjavík (E.S.B.). Address reprint requests to Dr. Hoofnagle at the Liver Disease Research Branch, Rm. 6005, Democracy II, 6707 Democracy Blvd., Bethesda, MD 20892, or at hoofnaglej@nih.gov.

 

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