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 actions concerning drugs, including failure to gain 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). One of the initial projects to be conducted by this 5 center network is to retrospectively establish a nationwide registry of patients who have suffered severe idiosyncratic liver injury associated with drugs (ILIAD), and to collect, immortalize and store serum, DNA, and lymphocytes from these patients (hereafter referred to as the "ILIAD protocol"). This ILIAD protocol will serve as a resource for subsequent mechanistic investigations of the basis for susceptibility to severe idiosyncratic DILI. The study subjects will be divided into two groups, cases and controls. Cases are individuals who suffered drug-induced liver injury due to isoniazid, phenytoin, combination clavulanic acid / amoxicillin, or valproic acid. Case patients may have undergone liver transplantation but the DILI episode must have occurred after January 1, 1994. Subjects will be excluded if they are unable to provide informed consent for participation or are not willing to have medical information or a blood sample drawn for research purposes. Because this study is intended to examine clinical, environmental, and genetic risk factors for DILI in patients treated with one of the targeted drugs, control subjects will be individuals treated with one of the targeted drugs who did not develop DILI. A matched design is employed with each case individually matched with one control based on (a) age at the time of the DILI event, (b) minimum duration of drug therapy, and (c) clinical setting and/or indication for drug therapy.