Laboratory-based biomarkers to improve causality assessment in drug-induced liver injury.
Laboratory-based biomarkers to improve causality assessment in drug-induced liver injury.
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DOI：
10.1002/cld.611
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发表时间：
2017-02-01
影响因子：
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通讯作者：
Antoine, Daniel J
中科院分区：
文献类型：
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作者：
Antoine, Daniel J
药物性肝损伤（DILI）是与患者发病率和死亡率相关的主要医学问题。在药物开发过程中，DILI引起的损耗发生在从临床前测试到临床试验再到市场的各个阶段。DILI主要分为两种形式：内在DILI和特质DILI。在动物或人类中出现频率高的情况下，DILI被认为是内在的，因为它被认为是由直接的肝细胞损伤引起的。特异性DILI很少发生在暴露于治疗剂量的易感个体中，但可能代表严重的药物不良反应。对于继发于潜在肝毒性药物的肝功能检查紊乱的患者，应考虑使用该药物。由于疾病机制的复杂性，特异性DILI是不可预测的。目前，DILI的诊断是基于排除。排除其他差异原因和了解与潜在肝毒素施用的时间关系是建立DILI诊断的基石。对于因果关系评估，不同的方法，如罗素- uclaf因果关系评估方法（RUCAM）或基于共识的专家意见方法是使用的两种主要机制。尽管相对强大，但每种机制也有一些局限性。一个主要
Drug-induced liver injury (DILI) represents a major medical concern associated with significant patient morbidity and mortality. Within drug development, attrition caused by DILI occurs in all phases of the pipeline, from preclinical testing to clinical trials to the marketplace. DILI is largely categorized into two major forms: intrinsic and idiosyncratic. In cases where the frequency is high in either animal species or in humans, DILI is considered intrinsic in that it is assumed to result from direct hepatocellular damage. Idiosyncratic DILI occurs rarely in susceptible individuals exposed to therapeutic doses but can represent a serious adverse drug reaction. 1 It should be considered in patients who have deranged liver function tests secondary to the administration of a potentially hepatotoxic agent. Idiosyncratic DILI is unpredictable because of the complex nature of the mechanisms of the disease.Currently, the diagnosis of DILI is based on exclusion. The exclusion of other differential causes and an understanding of the temporal relationship to the administration of a potential hepatotoxin represent the cornerstone for establishing a diagnosis of DILI. For causality assessment, different methods such as the Roussel-Uclaf Causality Assessment Method (RUCAM) or a consensusbased expert opinion approach are two main mechanisms used. 2 Despite relative strength, each mechanism is also associated with a number of limitations. A major