Risk factors for idiosyncratic drug-induced liver injury.
Risk factors for idiosyncratic drug-induced liver injury.
复制标题
DOI：
10.1053/j.gastro.2010.04.001
复制
发表时间：
2010-06
期刊：
影响因子：
29.4
通讯作者：
Björnsson E
中科院分区：
文献类型：
--
作者：
Chalasani N;Björnsson E
特异质药物性肝损伤（DILI）是一种罕见的疾病，与剂量没有直接关系，对风险增加的个体知之甚少。目前还没有适合研究特异质DILI的临床前模型，其发病机制也知之甚少。它可能是由遗传、非遗传宿主易感性和环境因素之间复杂的相互作用引起的。非遗传性风险因素包括年龄、性别和其他疾病（如慢性肝病或人类免疫缺陷病毒感染）。化合物特异性风险因素包括每日剂量、代谢特征和药物相互作用倾向。饮酒被认为是药物引起DILI的一个危险因素，但没有足够的证据支持这一点。许多研究探索了可能参与发病机制的遗传缺陷，并集中在参与药物代谢和免疫反应的基因上。DILI患者的多中心数据库（美国药物性肝损伤网络，DILIGEN和西班牙DILI登记处）是临床和遗传研究的重要工具。氟氯西林肝毒性的全基因组关联研究已经取得了突破性的结果，许多类似的研究正在进行中。尽管如此，DILI是具有挑战性的调查，因为它的罕见性，缺乏实验模型，可能导致它的药物数量，以及诊断的挑战。
Idiosyncratic drug-induced liver injury (DILI) is a rare disorder that is not related directly to dosage and little is known about individuals who are at increased risk. There are no suitable preclinical models for the study of idiosyncratic DILI and its pathogenesis is poorly understood. It is likely to arise from complex interactions among genetic, nongenetic host susceptibility, and environmental factors. Nongenetic risk factors include age, sex, and other diseases (eg, chronic liver disease or human immunodeficiency virus infection). Compound-specific risk factors include daily dose, metabolism characteristics, and propensity for drug interactions. Alcohol consumption has been proposed as a risk factor for DILI from medications, but there is insufficient evidence to support this. Many studies have explored genetic defects that might be involved in pathogenesis and focused on genes involved in drug metabolism and the immune response. Multicenter databases of patients with DILI (the United States Drug Induced Liver Injury Network, DILIGEN, and the Spanish DILI registry) are important tools for clinical and genetic research. A genome-wide association study of flucloxacillin hepatotoxicity has yielded groundbreaking results and many similar studies are underway. Nonetheless, DILI is challenging to investigate because of its rarity, the lack of experimental models, the number of medications that might cause it, and challenges to diagnosis.
登录
查看更多内容
影响因子：
13.5
作者：
Andrade, RJ;Lucena, MI;Hidalgo, R
通讯作者：
Hidalgo, R
影响因子：
25.7
作者：
Brunetto, MR;Oliveri, F;Bonino, F
通讯作者：
Bonino, F
影响因子：
29.4
作者：
Andrade, RJ;Lucena, MI;Martin-Vivaldi, R
通讯作者：
Martin-Vivaldi, R
影响因子：
13.5
作者：
Björnsson, E;Olsson, R
通讯作者：
Olsson, R
影响因子：
25.7
作者：
Bjornsson, Einar;Davidsdottir, Loa
通讯作者：
Davidsdottir, Loa