Collaborative Clinical Research on Hepatotoxicity

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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.