IDIOSYNCRATIC LIVER INJURY ASSOCIATED WITH DRUGS ILIAD: A RETROSPECTIVE STUDY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。药物性肝损伤（DILI）是药物监管行动的最常见原因，包括未能获得上市批准、从市场上移除以及处方适应症的限制。DILI也是许多患者发病和死亡的一个重要原因。为了刺激和促进对DILI的研究，国家糖尿病、消化和肾脏疾病研究所（NIDDK）最近建立了药物性肝损伤网络（DILIN）。该中心网络开展的最初项目之一是回顾性地建立一个全国性的严重药物相关特异性肝损伤患者登记册（ILIAD），并收集、永久保存这些患者的血清、DNA和淋巴细胞（以下简称“ILIAD方案”）。该ILIAD方案将作为对严重特异性DILI易感性基础的后续机制调查的资源。研究对象将被分为两组，病例组和对照组。病例是由于异烟肼、苯妥英、克拉维酸/阿莫西林联合或丙戊酸而遭受药物性肝损伤的个体。病例患者可能接受过肝移植，但DILI发作必须发生在1994年1月1日之后。如果受试者无法提供参与的知情同意或不愿意为研究目的提供医疗信息或抽取血液样本，则受试者将被排除在外。由于本研究旨在检查使用一种靶向药物治疗的患者DILI的临床、环境和遗传风险因素，因此对照受试者将是使用一种靶向药物治疗的未发生DILI的个体。采用匹配设计，根据(A) DILI事件发生时的年龄，(b)药物治疗的最短持续时间，以及(c)药物治疗的临床环境和/或适应症，将每个病例单独与一个对照进行匹配。

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.