The Drug Induced Liver Injury Network (DILIN): Focus on Herbal and Dietary Supplements

项目总结 爱因斯坦医学中心将继续为三种DILIN方案招募病例； 并参与其所有程序和辅助研究。在爱因斯坦，我们将 将我们的研究重点放在草药和膳食补充剂(HDS)对肝脏的损伤上。具体地说，我们的 采取这种办法将需要扩大由于HDS，特别是早期感染的DILI病例的预期登记人数 伤害，使用一种称为搜索引擎优化的创新营销方法，借此互联网将 作为一种招募工具被利用。我们将支持对从DILIN收集的HDS进行持续的化学分析 与加州大学国家天然产品研究中心(NCNPR)合作的参与者 密西西比州。为了更全面地描述与HDS相关的肝损伤，我们将监督几个 活动。首先，我们将与来自NIH的David Kleiner博士一起详细回顾 与HDS肝损伤相关的组织病理学通过化学分析和 详细的临床信息。第二，我们将监督对以前判决的案件进行逐案审查， 考虑到最新的HDS化学分析，建议对最终因果关系进行调整 视情况而定的决定。第三，我们将进行嵌套病例/对照研究，以确定这些因素 与使用HDS有关，这会影响发生肝损伤的几率。这笔赠款还将探索 HDS的毒性，重点是绿茶提取物，HDS的一种常用成分，有 毒性的重要证据；我们的发现将为科学家、监管机构和消费者提供关于 这种成分的安全使用，并确定了一种进一步研究其他天然产品的方法 配料。最后，我们将减少产品分析的周转时间，从而提炼DILIN因果关系 评估过程，将化学分析结果纳入其裁决过程。这个更快的转弯- 约时间还将促进与食品和药物管理局合作的药物警戒工作 行政部门。我们还将与疾病预防控制中心合作，支持最终的早期预警系统 通过提供确诊HDS的产品和未确认的病例信息，暴发HDS引起的肝损伤 HDS造成肝脏损伤的病例；这些信息将使人们能够检测到可归因性肝脏损伤的暴发。 为了支持我们的所有目标，我们将继续监督和发展HDS存储库，将其作为 狄林。

PROJECT SUMMARY The Einstein Medical Center will continue to recruit cases for the three DILIN protocols; prospective, retrospective, and acute, and to participate in all of its procedures and ancillary studies. At Einstein, we will focus our investigative approach on liver injury from Herbal and Dietary Supplements (HDS). Specifically, our approach will entail expansion of prospective enrollment of DILI cases due to HDS, especially those with early injury, using an innovative marketing method termed Search Engine Optimization, whereby the internet will be exploited as a recruitment tool. We will support ongoing chemical analysis of HDS collected from DILIN enrollees in collaboration with the National Center for Natural Products Research (NCNPR) at the University of Mississippi. In order to more fully characterize liver injury associated with HDS, we will oversee several activities. First, we will participate with Dr. David Kleiner from the NIH in a detailed review of the histopathology associated with liver injury from HDS by informing his review with chemical analysis and detailed clinical information. Second, we will oversee a case-by-case review of previously adjudicated cases, taking into consideration newly available chemical analyses of HDS, proposing adjustment to final causality determinations as appropriate. Third, we will, conduct a nested case/control study to identify those factors associated with use of HDS that affect the odds of developing liver injury. This grant will also explore the toxicity of HDS, focusing on Green Tea Extract, a commonly used ingredient of HDS for which there is significant evidence for toxicity; our findings will provide guidance to scientists, regulators, and consumers on the safe use of this ingredient, and define an approach to further research with other natural product ingredients. Finally, we will reduce the turn-around time for product analysis, thus refining the DILIN causality assessment process by incorporating chemical analysis results into its adjudication process. This quicker turn- around time will also facilitate pharmacovigilance efforts in collaboration with the Food and Drug Administration. We will also collaborate with the CDC to support an eventual early warning system for outbreaks of liver injury due to HDS by providing product and de-identified case information on confirmed cases of liver injury due to HDS; this information will allow the detection of outbreaks of attributable liver injury. To support all of our aims, we will continue to oversee and DILIN HDS repository as a critical resource of the DILIN.