University of North Carolina Clinical Center for DILIN

Abstracts Since the inception Drug-Induced Liver Injury Network (DILIN) in 2003, the University of North Carolina Clinical Center have led all DILIN centers in total subject recruitment, participation in DILIN's subcommittees, execution of ancillary studies, and authorship on DILIN publications. In the next 5 years, we propose to continue our center's leadership as the network strives to attain the four stated goals of the RFA: 1. Advance the clinical, biochemical, histologic and biologic characterization of DILI. We will continue to participate in, or lead, all subcommittees, and the majority of ancillary studies and publications. We will expand our access to minority patients through a new Community Health Care Network coordinated by an historically black university. 2. Lead in the proposal and execution of ancillary studies and collaborations that would investigate basic mechanisms of liver injury due to specific drugs and provide insights into pathogenesis of DILI and potential targets for prevention and treatment. We will continue to support DILIN's pioneering work on Genetic Risk Scores, their mechanistic insight, and their clinical application. We will also guide discovery and application of promising non-genetic biomarkers through collaborations with the major European biomarker initiative (Transbioline), the National Institutes for Environmental Health Sciences, and potentially with a lead company in clinical application of metabolomics. 3. Develop pilot/feasibility studies that would lay the groundwork for future studies on treatment of DILI. Our center is well positioned to participate in a proposed open label pilot study of budesonide. 4. Promote pharmacovigilance of HDS and newly approved prescription medications (collaboration with FDA) and public resources for accurate information on DILI (DILIN centers and Livertox). We will help improve the new Revised Electronic Causality Assessment Method (RECAM) instrument, including incorporation of genetic risk scores, which should soon be adopted in assessment of clinical trial and early post-marketing DILI cases. We will help mentor, along with FDA colleagues, an FDA supported ORISE fellow to improve prediction of liver injury severity using traditional liver safety biomarkers. All four of our center's investigators will continue help build and improve the Livertox website. In summary, we believe we are well poised to help guide the accelerated rate of discovery and clinical application that will occur in the next 5 years and are very excited about it.