A MULTICENTER, LONGITUDINAL STUDY OF DRUG AND CAM-INDUCED LIVER INJURY

药物和 CAM 引起的肝损伤的多中心纵向研究

• 批准号: 7608452
• 负责人: James H. Lewis
• 金额: $ 4.39万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608452
• 关键词: Affect; Biological; Blood; Case Study; Clinical; Clinical Data; Computer Retrieval of Information on Scientific Projects Database; DNA; Detection; Diagnosis; Drug Exposure; Drug Formulations; Environmental Risk Factor; Etiology; Food Additives; Frequencies; Funding; Future; Genetic; Goals; Grant; Health; Hepatotoxicity; Individual; Injury; Institution; Liver; Longitudinal Studies; Mandatory Reporting; Mediating; Medical; Medical Surveillance; Monitor; Patients; Pharmaceutical Preparations; Prospective Studies; Public Health; Recording of previous events; Registries; Reporting; Research; Research Design; Research Personnel; Resources; Sampling; Signal Transduction; Source; Specimen; System; Terminology; Testing; Tissues; United States; United States Food and Drug Administration; United States National Institutes of Health; Urine; Withdrawal; abstracting; authority; clinically significant; drug development; follow-up; genetic risk factor; improved; instrument; post-market; prescription document; prescription procedure

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. Abstract: Liver injury due to prescription and non-prescription medication use is a medical, scientific, and public health problem of increasing frequency and importance in the United States. Indeed, drug-induced liver injury (DILI) is the most common reason for nonapproval, withdrawal, limitation in use, and clinical monitoring by the Food and Drug Administration (FDA). However, detection of signals for liver injury frequently relies upon the reporting of cases by practitioners to health authorities in post-marketing surveillance. Underreporting of cases, lack of mandatory reporting systems, and difficulties in establishing a diagnosis make the current system sub-optimal. Moreover, with the growing use of complementary and alternative medications (CAM), there have also been increasing reports of liver toxicity due to various non-prescription herbal, dietary, and food additive supplements. Because the manufacturing, dispensing, and testing of these products is not regulated, the hepatotoxic potential of these formulations is poorly characterized or completely unknown. As a result, there is a great need to develop an improved means of detecting, defining, and studying DILI in the United States. The DILIN prospective study is a multi-center study designed to gather clinical information and biological specimens on cases of suspected liver injury due to drugs and CAM. The goals of this study include the earlier recognition of DILI, especially due to newer drugs, development of standardized instruments and terminology to help identify cases of DILI, investigating clinical and genetic risk factors that predict DILI, and performing a careful longitudinal follow-up of DILI subjects. The biological samples collected will be used in future studies of the mechanisms and genetics of DILI. The primary objective of this study is to prospectively identify bona fide cases of liver injury due to drugs and complementary and alternative medications within 6 months of presentation. Secondary objectives include collecting clinical data and biological specimens including blood, DNA, urine, and liver tissue from affected patients and matched controls for future mechanistic and genetic studies. We will also investigate the clinical, immunological, and environmental risk factors of drug-mediated hepatotoxicity by comparing DILI cases to matched controls with a similar drug exposure history but no evidence of clinically significant liver injury. We will also develop and test causality assessment instruments for drug and CAM-induced liver injury that are sensitive, specific, and reproducible. This information will be compiled into a registry that will be in existence for up to 20 years to afford the possibility of future contact of individuals for other studies.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要： 由于处方和非处方药物使用导致的肝损伤是美国日益频繁和重要的医学，科学和公共卫生问题。 事实上，药物性肝损伤（DILI）是美国食品药品监督管理局（FDA）不予批准、撤回、限制使用和临床监测的最常见原因。 然而，肝损伤信号的检测通常依赖于从业人员在上市后监测中向卫生监管机构报告病例。 病例报告不足，缺乏强制性报告制度，以及难以作出诊断，使目前的制度不够理想。 此外，随着补充和替代药物（CAM）的使用越来越多，由于各种非处方草药，饮食和食品添加剂补充剂而引起的肝毒性报告也越来越多。 由于这些产品的生产、分配和检测不受监管，因此这些制剂的肝毒性潜力特征不佳或完全未知。 因此，在美国非常需要开发一种改进的检测、定义和研究DILI的方法。DILIN前瞻性研究是一项多中心研究，旨在收集药物和CAM引起的疑似肝损伤病例的临床信息和生物标本。 本研究的目标包括早期识别DILI，特别是由于新药，开发标准化工具和术语以帮助识别DILI病例，调查预测DILI的临床和遗传风险因素，并对DILI受试者进行仔细的纵向随访。 收集的生物样本将用于DILI机制和遗传学的未来研究。 本研究的主要目的是前瞻性地确定在6个月内由于药物和补充和替代药物引起的真正肝损伤病例。 次要目的包括收集临床数据和生物标本，包括受影响患者和匹配对照的血液、DNA、尿液和肝组织，用于未来的机制和遗传研究。 我们还将通过比较DILI病例与具有相似药物暴露史但无临床显著肝损伤证据的匹配对照，研究药物介导的肝毒性的临床、免疫学和环境风险因素。 我们还将开发和测试药物和CAM诱导的肝损伤的因果关系评估工具，这些工具具有敏感性，特异性和可重复性。 这些信息将被汇编到一个登记处，该登记处将存在长达20年，以便将来有可能联系个人进行其他研究。