IDIOSYNCRATIC LIVER INJURY ASSOCIATED WITH DRUGS (ILIAD): A RETROSPECTIVE STUDY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Drug-induced liver injury (DILI) is the single most common reason for regulatory failure for drugs, including failure to gain FDA approval for marketing, removal from the market place, and restriction of prescribing indications. DILI is also a significant cause of morbidity and mortality in many patient populations. To stimulate and facilitate research into DILI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has recently established the Drug-Induced Liver Injury Network (DILIN). Indiana University is one of the five clinical centers for DILIN and Dr. Chalasani is the PI for the IU-clinical center. One of the initial projects to be conducted by the network is to establish a nationwide retrospective registry of patients who have suffered severe idiosyncratic liver injury associated with 4 specific drugs (ILIAD), and to collect, immortalize and store serum, DNA, and lymphocytes from these patients (hereafter referred to as the "ILIAD protocol"). Four agents to be studied in ILIAD include phenytoin, valproate, amoxicillin/clavulanate and isoniazid. These four agents are chosen because (a) these are commonly used medications and DILI, (b) DILI is a significant problem from each of these agents and (c) each of these agents is thought to cause DILI in a distinct way from the pathogenesis point of view (e.g., valproate causes mitochondrial injury whereas amox/clavulanate causes cholestatic injury).