IDIOSYNCRATIC LIVER INJURY ASSOCIATED WITH DRUGS ILIAD: A RETROSPECTIVE STUDY

与药物伊利亚特相关的特异质性肝损伤：一项回顾性研究

• 批准号: 7376599
• 负责人: ROBERT J FONTANA
• 金额: $ 0.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376599
• 关键词: chemotherapy; injury; liver

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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、从市场上撤市和限制处方适应症。DILI也是许多患者人群发病和死亡的重要原因。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）。由这5个中心网络进行的初始项目之一是回顾性地建立患有与药物相关的严重特异质肝损伤（ILIAD）的患者的全国登记，并收集、永生化和储存来自这些患者的血清、DNA和淋巴细胞（下文称为“ILIAD方案”）。该ILIAD方案将作为后续对重度特异质DILI易感性基础的机制研究的资源。 研究对象将被分为两组，病例组和对照组。病例是因异烟肼、苯妥英、克拉维酸/阿莫西林或丙戊酸联合用药而发生药物性肝损伤的个体。病例患者可能接受了肝移植，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研究的知情同意书或不愿意提供医学信息或采集用于研究目的的血液样本，则将其排除。由于本研究旨在检查接受其中一种靶向药物治疗的患者中DILI的临床、环境和遗传风险因素，因此对照受试者将是接受其中一种靶向药物治疗但未发生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，和（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组匹配。