UT Southwestern: Clinical Site for the Drug-Induced Liver Injury Network

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DESCRIPTION (provided by applicant): Drug-induced liver injury (DILI) is one of the most difficult problems encountered in clinical medicine. Unexpected DILI has hampered drug development for a multitude of effective drugs. Many agents have been approved or nearly approved but failed to gain widespread acceptance because of severe and sometimes fatal DILI. The small size of pre-approval trials means that infrequent events will not be captured. Thus, aggressive, robust, and measured approaches to post-marketing surveillance for adverse events due to drugs and their characterization is vital to the health of all Americans. The Drug-Induced Liver Injury Network (DILIN) has made a strong start in laying the groundwork in its first 5 years, having put in place systems that can be used more widely in the future. Thus, an opportunity exists to enhance capture of additional cases of post-marketing DILI so as to improve our understanding of its causes and. potentially, its treatment. UT Southwestern is ideally suited to become a DILIN site for the following reasons: 1) the Dallas Fort Worth metroplex constitutes a widely diverse urban/suburban population of over 6.5 million people. 2) the investigators have specific and strong experience in DILI and clinical trials development, Our specific proposals include: 1) An advisory board of clinicians in the region to refer cases. We will consult them frequently, provide a 1-800 number for their calls and visit sites for in service updates and discussion of drugs of importance in causing DILI. 2) We will utilize the experience of the investigators in the Acute Liver Failure Study to expand and encourage further ancillary studies utilizing DILI biomaterials. Specific substudies should be possible with the large Hispanic population currently under study at our institution. 3) We propose a therapeutic trial using N-acetylcysteine for DILI cases that meet criteria for severe injury approximating Hy Zimmerman's law, that is, an acute illness with attendant jaundice.