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

与药物相关的特异质性肝损伤（ILIAD）：一项回顾性研究

• 批准号: 7606427
• 负责人: NAGA P CHALASANI
• 金额: $ 0.05万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606427
• 关键词: Amoxicillin; Clavulanate; Clinical; Computer Retrieval of Information on Scientific Projects Database; DNA; Diabetes Mellitus; Excision; Failure; Funding; Grant; Indiana; Injury; Institutes; Institution; Kidney Diseases; Liver; Lymphocyte; Marketing; Mitochondria; Morbidity - disease rate; Pathogenesis; Patients; Pharmaceutical Preparations; Phenytoin; Population; Protocols documentation; Research; Research Personnel; Resources; Retrospective Studies; Serum; Source; Thinking; United States Food and Drug Administration; United States National Institutes of Health; Universities; isoniazid; mortality; patient registry; valproate

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).

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 药物性肝损伤(DILI)是药品监管失败的最常见原因，包括未能获得FDA批准上市、从市场上下架以及限制开药适应症。在许多患者群体中，DILI也是发病率和死亡率的重要原因。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)最近建立了药物诱导肝损伤网络(DILIN)。印第安纳大学是DILIN的五个临床中心之一，Chalasani博士是IU临床中心的PI。该网络将开展的初步项目之一是建立一个全国范围内因4种特定药物(伊利亚特)而遭受严重特异性肝损伤的患者的追溯登记，并收集、永生化和储存这些患者的血清、DNA和淋巴细胞(以下称为“伊利亚特方案”)。在伊利亚特中研究的四种药物包括苯妥英、丙戊酸盐、阿莫西林/克拉维酸和异烟肼。之所以选择这四种药物，是因为(A)这些都是常用的药物和DILI，(B)DILI是这些药物中的每一种都存在的重大问题，以及(C)从发病机制的角度来看，这些药物中的每一种都被认为是导致DILI的不同方式(例如，丙戊酸盐导致线粒体损伤，而AmoX/Clavulanate导致胆汁淤积损伤)。