Prospective Surveillance Drug and HDS-Induced Liver Injury

药物和 HDS 引起的肝损伤的前瞻性监测

• 批准号: 9132249
• 负责人: VICTOR J NAVARRO
• 金额: $ 49.1万
• 依托单位: ALBERT EINSTEIN HEALTHCARE NETWORK
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132249
• 关键词: Algorithms; Antibiotics; Clinical; Collaborations; Communities; Computers; Delaware; Electronic Health Record; Etiology; Funding; Gastroenterologist; Genetic Research; Herbal supplement; Individual; Informatics; Injury; Integration Host Factors; Lead; Medical; Patients; Pharmaceutical Preparations; Process Assessment; Reporting; Research; Resources; Sampling; Scientist; Serum; Shapes; Specialist; Tissues; Toxicology; United States National Institutes of Health; Validation; Work; adverse outcome; base; case-based; design; insight; instrument; liver injury; meetings; population based; prospective; public health relevance; repository

DESCRIPTION (provided by applicant): The Drug Induced Liver Injury Network (DILIN), funded by the National Institutes of Health, represents a critical strategy to mitigate the adverse consequences of DILI. Already, this extensive network of centers around the U.S. has cultivated an impressive repertoire of case based clinical information and samples which has given important insights into DILI in the U.S. Some of the salient findings that have shaped our understanding of DILI and impact future research plans include the observation that antibiotics are the most common class of agents implicated in DILI, followed by Herbal and Dietary Supplements (HDS). The specific aims of this o Application are as follows: 1) To accrue early DILI cases, and collect serum, tissue, and clinical information on those patients meeting entry criteria through three mechanisms: Gastroenterologist- based; electronic health record (EHR); and population-based surveillance; 2) To continue to administer the DILIN Repository for Herbal and Dietary Supplements (HDS) and facilitate collaborative descriptive and product analysis and genetics research to identify injurious agents and host factors responsible for HDS induced liver injury (HILI); 3) To lead DILIN's effort in the causality assessment process for HILI, including it validation, and contribute to its incorporation into a computer-based instrument that is practical for clinicians and applicable for assessment of injury due to both drugs and HDS; 4) To contribute to the expansion of the Herbal and Dietary Supplement component of LiverTox and facilitate the use of LiverTox as a mechanism for DILI reporting by the medical community at large. To accomplish these aims, key collaborations have been built. Informatics specialists will assist in the design, implementation, validation, and refinement of an electronic health record algorithm. Collaborations have also been built with geneticists and the FDA toxicology group to explore the mechanisms for idiosyncratic liver injury from HDS, as well as to identify the agents responsible for injury. Our research will further refine causality assessment, particularly as it pertains to HILI. Finally, the proposed work will expand the functionality of LiverTox, both as a resource for the clinician and clinical scientist, as well as the individual seeking to report a cae of DILI or HILI.

描述（由申请人提供）：由美国国立卫生研究院资助的药物诱导肝损伤网络（DILIN）是减轻不利的关键策略 DILI的后果。在美国，这个广泛的中心网络已经培养了令人印象深刻的基于病例的临床信息和样本的曲目，这些信息对美国的DILI有了重要的见解，其中一些显着的发现塑造了我们对DILI的理解和未来的研究计划，并观察到抗生素包括抗生素是DILI中最常见的药物，含有DILI，随后是Herbal and Dietantary and Herbal and Dietantary and Degermental（Hds）。该O应用的具体目的如下：1）累积早期DILI病例，并通过三种机制收集有关符合入境标准的患者的血清，组织和临床信息：基于胃肠病医生；电子健康记录（EHR）；和基于人群的监视； 2）继续管理草药和饮食补充剂（HDS）的稀释库，并促进协作性描述性和产品分析以及遗传学研究，以识别负责HDS诱导肝损伤（HILI）的有害药物和宿主因素； 3）领导Dilin在HILI的因果关系评估过程中的努力，包括IT验证，并有助于将其纳入基于计算机的工具，该工具适用于临床医生实用，适用于由于药物和HDS而造成的伤害； 4）有助于扩大Livertox的草药和饮食补充剂成分，并促进使用Livertox作为整个医学界的DILI报告的机制。为了实现这些目标，已经建立了主要的合作。信息学专家将协助电子健康记录算法的设计，实施，验证和完善。还与遗传学家和FDA毒理学组建立了合作，以探索HDS造成的特质肝损伤机制，并确定负责损伤的药物。我们的研究将进一步完善因果关系评估，特别是与希利有关。最后，拟议的工作将扩大Livertox的功能，无论是作为临床医生和临床科学家的资源，以及寻求报告DILI或HILI CAE的个人。