Recognizing drug-induced liver injury: Current problems, possible solutions
Recognizing drug-induced liver injury: Current problems, possible solutions
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DOI：
10.1080/01926230590522356
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发表时间：
2005-01-01
影响因子：
1.5
通讯作者：
Senior, JR
中科院分区：
文献类型：
--
作者：
Lee, WM;Senior, JR
目前，了解药物性肝损伤（DILI）存在三个主要问题：（1）可靠地确定肝脏疾病是否由药物或其他过程引起;（2）确定药物性肝毒性的真实发生率和临床风险因素;（3）阐明肝细胞和其他肝细胞发生损伤的机制。我们在这里集中讨论了前两个问题，因为这些问题可能在不久的将来就可以采取行动，但第三个问题可能需要更长的时间才能解决。第一个问题需要足够的信息进行医学鉴别诊断。没有DILI的特征性指标，甚至肝活检也不能诊断。正确的因果关系归因需要分析药物暴露与疾病的时间关系，并排除所有其他可能的原因。第二个问题，确定发病率，不能完全充分地使用现有的方法，无论是通过临床试验，通过自发的不良事件报告，或通过回顾性流行病学研究。有必要进行前瞻性安全性研究，以确定药物引起的DILI的真实发生率，确定其风险因素，并收集生物材料进行分析研究，以更好地了解DILI的机制。
Currently there are three major problems in understanding drug-induced liver injury (DILI): (1) reliably establishing whether the liver disease was caused by the drug, or by another process: (2) determining the true incidence of and clinical risk factors for drug-induced hepatotoxicity; and (3) elaborating the mechanisms by which injury occurs to hepatocytes and other liver cells. We have focused here on the first two problems, as issues that may be amenable to actions in the near future, but the third may take substantially longer to work out. The first problem requires sufficient information for medical differential diagnosis. There are no pathognomonic indicators of DILI; even liver biopsy is not diagnostic. Making the correct attribution of causality requires analyzing the temporal relationship of drug exposure to illness and excluding all other possible causes. The second problem, determining incidence, cannot be done entirely adequately using Currently available methods, whether by clinical trials, by spontaneous adverse event reports, or by retrospective epidemiologic studies. There is need for prospective safety studies to establish the true incidence of DILI caused by a drug, to identify risk factors for it, and to collect biologic materials for analytic studies toward better understanding mechanisms of DILI.