Collaborative Clinical Research on Hepatotoxicity

描述(由申请人提供)： 药物性肝损伤通常是轻微的，导致肝脏生化指标的一过性升高，但有时会导致严重的肝损伤，导致死亡或肝移植。由于越来越多的美国人口使用药物以及补充和替代药物(CAM)，其临床负担预计将恶化。然而，缺乏关于药物肝毒性的流行病学、诊断、危险因素、机制和结果的数据。为了更好地了解药物肝毒性的流行病学和发病机制，我们建议开展药物肝毒性的相关研究，具体目的如下：具体目的1：收集大量疑似药物、中草药或毒素引起的肝毒性患者，以便将其纳入药物肝毒性数据库。我们建议从多个来源收集药物肝毒性的横断面和预期病例和适当的对照，每个来源都提供独特的流行病学方面和研究潜力。我们将利用Regenstrief卫生保健研究所建立的医疗信息学系统来识别捕获的药物肝毒性疑似病例，并开发药物肝毒性数据库，使我们能够对药物肝毒性进行多学科、多中心的研究。这个数据库将包括成人和儿童的药物肝毒性和适当的对照。这个数据库将根据违法者的性质(毒品、毒素和CAM)进行分层。数据库中的受试者将通过实验室测试和组织学(只要有)进行临床特征描述。具体目标#3：目标是利用生化、血清学和基因技术，从具有药物肝毒性的受试者中开发生物样本(血液、尿液、DNA样本和肝组织可用)的储存库。我们建议样本知情同意收集和使用DNA用于当前和未来的遗传学研究。我们还提出了一种策略，利用已建立的NIGMS药物遗传学核心实验室来识别可能导致药物肝毒性的遗传变异。

DESCRIPTION (provided by applicant): Drug Induced liver injury is usually mild resulting in transient elevations in liver biochemistries, but sometimes can cause sever liver injury leading to death or liver transplantation. Its clinical burden is anticipated to worsen due to increasing number of U.S. population consuming medications and complementary and alternative medicines (CAM). However, there is a paucity of data regarding the epidemiology, diagnosis, risk factors, mechanisms, and outcomes of drug hepatotoxicity. In order to better understand the epidemiology and pathogenesis of drug hepatotoxicity, we propose to conduct drug hepatotoxicity-related research with the following specific aims: Specific Aim #1: The objective is to collect a large number of patients with suspected hepatotoxicity caused by drugs, herbals, or toxins in order to enroll them into a drug hepatotoxicity database. We propose to collect cross-sectional and prospective cases of drug hepatotoxicity and appropriate controls from multiple sources, each providng distinctive epidemiological facets and research potential. We will utilize the medical informatics system established by the Regenstrief Institute for Health Care to identify suspected cases of drug hepatotoxicity captured and to develop a database of drug hepatotoxicity that will enable us to conduct multidisciplinary, multicenter studies on drug hepatotoxicity. This database will consist of adults and children with drug hepatotoxicity and appropriate controls. This database will be stratified according to the nature of offending agent (drugs vs toxins vs CAM). The subjects in the database will be characterized clinically, through laboratory tests and histologically (whenever available). Specific Aim # 3: The objective is to develop a repository of biological samples (blood, urine, and DNA sample and liver tissue whenever available) from] subjects with drug hepatotoxicity using biochemical, serological, and genetic techniques. We propose a sample informed consent for collecting and using DNA for current and future genetic studies. We also propose a strategy for identifying genetic variations that may cause drug hepatotoxicity using an established NIGMS Pharmacogenetic Core Laboratory.