Prospective Surveillance Drug and HDS-Induced Liver Injury

描述（由申请人提供）：由美国国立卫生研究院资助的药物性肝损伤网络（DILIN）代表了减轻不良反应的关键策略。 DILI的后果这个遍布美国的广泛的中心网络已经培养了一个令人印象深刻的基于病例的临床信息和样本库，这为美国的DILI提供了重要的见解。一些突出的发现塑造了我们对DILI的理解并影响了未来的研究计划，包括观察到抗生素是DILI中最常见的一类药物，其次是草药和膳食补充剂（HDS）。本申请的具体目的如下：1）通过三种机制累积早期DILI病例，并收集符合入选标准的患者的血清、组织和临床信息：基于胃肠病学家的;电子健康记录（EHR）;和基于人群的监测; 2）继续管理DILIN草药和膳食补充剂库（HDS）并促进合作的描述性和产品分析以及遗传学研究，以确定导致HDS诱导的肝损伤（HILI）的有害物质和宿主因素; 3）领导DILIN在HILI因果关系评估过程中的工作，包括其验证，并将其纳入基于计算机的工具中，该工具对临床医生实用，适用于药物和HDS所致损伤的评估; 4）促进扩大LiverTox的草药和膳食补充剂成分，并促进LiverTox作为整个医学界DILI报告的机制。为了实现这些目标，已经建立了关键的合作。信息学专家将协助设计，实施，验证和完善电子健康记录算法。还与遗传学家和FDA毒理学小组建立了合作，以探索HDS引起的特异质肝损伤的机制，并确定造成损伤的药物。我们的研究将进一步完善因果关系评估，特别是当它涉及HILI时。最后，拟议的工作将扩展LiverTox的功能，作为临床医生和临床科学家的资源，以及寻求报告DILI或HILI病例的个人。

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.