Drug-induced liver injury.
Drug-induced liver injury.
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DOI：
10.7861/clinmedicine.16-6-s104
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发表时间：
2016-12
影响因子：
4.4
通讯作者：
D. Katarey;S. Verma
中科院分区：
文献类型：
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作者：
D. Katarey;S. Verma
药物性肝损伤（DILI）仍然是西方世界急性肝衰竭（ALF）的最常见原因。除扑热息痛过量外，临床环境中遇到的几乎所有DILI本质上都是特异质性的，因为受影响的个体仅占接受此类药物治疗的患者的一小部分。在许多情况下，特异质的机制是免疫介导的，并且通常通过人类白细胞抗原变体确定的遗传风险来识别。在缺乏诊断测试和/或生物标志物的情况下，DILI的诊断需要在努力排除肝脏检查异常的其他原因后高度怀疑。抗生素是最常与特异质DILI相关的一类药物，尽管最近的研究表明草药和膳食补充剂是一个越来越被认可的原因。发生DILI后，必须停用罪魁祸首药物，尤其是在转氨酶升高（天冬氨酸转氨酶/丙氨酸转氨酶比值≥5倍正常上限）和/或黄疸的情况下。发生ALF的风险因素包括肝细胞DILI和女性，治疗是支持性的，早期阶段N-乙酰半胱氨酸有一定获益。鉴于特异质DILI的无移植生存率低，必须早期考虑肝移植。
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identified by genetic risk determined by human leukocyte antigen variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, although recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued, especially in the presence of elevated transaminases (aspartate aminotransferase/alanine aminotransferase ratio ≥5 times the upper limit of normal) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefit of N-acetylcysteine in the early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory.