"Mount Sinai Regional Drug Induced Liver Injury Network Site"

描述(由申请人提供)：处方药和草药补充剂引起的肝脏毒性越来越被认为是整个发达国家发病率和死亡率的主要原因。由于其特殊的性质，不同的表现形式，以及大量潜在的致病药物以及草药和膳食补充剂，药物性肝损伤(DILI)通常在其病程后期被诊断为严重的 肝病。这使得诊断和确定与DILI发病有关的机制变得困难，而且无法准确评估与DILI相关的流行病学和风险因素。由于目前DILIN的主要问题之一是病例报告较晚，未来的调查应侧重于早期发现肝损伤的累积病例。NIDDK DILI研究中西奈山成员的目标如下：1)迅速增加登记的成人和儿童中患有DILI的人数，特别是在当前DILIN前瞻性和回溯性数据库中代表性不足的少数群体中；2)通过密切监测高危群体，招募在DILI过程中早期的患者；以及3)最终研究预防措施，以预防高危群体中的DILI。将西奈山纳入DILIN将导致来自西班牙裔、黑人和亚洲患者的帝力病例数量增加。将从纽约地区招募的大量亚洲和西班牙裔患者可能有助于深入了解与使用草药和膳食补充剂有关的肝损伤机制，因为众所周知，这些人群经常使用这些补充和替代药物。西奈山DILIN的一个主要组成部分将侧重于招募患有DILI的老年患者，重要的是还将重点放在服用这些补充剂的对照人群上，这一群体迄今在网络中没有得到很好的代表。同样，西奈山4000名艾滋病毒感染患者的庞大人口将提供病例和控制，以代表接受抗逆转录病毒治疗的大量人口。大量患者接受化疗，随后是许多西奈山肿瘤学家，这是未来帝力病例和对照的另一个理想来源。西奈山是Emerge的成员之一，Emerge是一个全国性的联盟，旨在开发、传播和应用使用电子医疗记录(EMR)系统进行基因组研究的方法。Emerge目前的一个项目是开发一种电子算法来识别EMR系统中的DILI病例。如果10万个Emerge DNA样本中只有1%有帝力的历史，那么DILIN可能会在一夜之间将其DNA样本数据库翻一番。西奈山的调查人员具备良好的资质，并准备为从大量可用数据和集体DILIN样本中产生的辅助研究做出贡献。结合卓越的基础设施，通过利用EMR和数据仓库收集详细信息，个性化医疗计划的合作伙伴关系，以及整个机构及其附属机构的多学科团队的参与，我们带来了巨大的人力来应对这个紧迫的问题。

DESCRIPTION (provided by applicant): Hepatotoxicity due to prescription medications and herbal supplements is increasingly recognized as a major cause of morbidity and mortality throughout the developed world. Due to its idiosyncratic nature, variable presentation, and the vast number of potential causative drugs as well as herbal and dietary supplements, drug-induced liver injury (DILI) is often diagnosed late in its course when patients present with severe liver disease. This makes diagnosis and characterization of the mechanisms involved in the pathogenesis of DILI, difficult and does not allow accurate assessment of the epidemiology and risk factors associated with DILI. Since one of the main concerns with the current DILIN is the late presentation of cases, future investigation should focus on accruing cases where the liver injury is detected early on. The aims of the Mount Sinai membership in the NIDDK DILI study are as follows: 1) To rapidly increase the number of enrolled adults and children with DILI, particularly among under-represented minority groups in the current DILIN prospective and retrospective databases; 2) To enroll patients early in the course of DILI by closely monitoring high risk groups; and 3) ultimately to investigate preventative measures to prevent DILI among high risk groups. The inclusion of Mount Sinai in the DILIN will lead to an increase in the number of DILI cases from Hispanic, Black and Asian patients. The significant number of Asian and Hispanic patients who will be recruited from the New York area may provide insights into the mechanism of liver injury related to the use of herbal and dietary supplements as these populations are known to be frequent users of these complementary and alternative medicines. A major component of the Mount Sinai DILIN will be focused on the recruitment of elderly patients with DILI, and importantly also on a control population taking these supplements, a population not well represented to date in the network. Similarly, Mount Sinai's large population of 4,000 HIV infected patients will provide cases and controls to represent the large population on antiretroviral therapy. The large number of patients undergoing chemotherapy treatment followed by the many Mount Sinai oncologists represents another ideal source of prospective DILI cases and controls. Mount Sinai is a member of eMERGE, a national consortium to develop, disseminate, and apply approaches using electronic medical records (EMR) systems to genomics research. A current projects in eMERGE is to develop an electronic algorithm to identify cases of DILI in EMR systems. If just 1 percent of the 100,000 eMERGE DNA samples have a history of DILI, then the DILIN could double its DNA sample database overnight. Investigators at Mount Sinai are well-qualified and poised to contribute to ancillary studies that arise from the wealth of available data and samples of the collective DILIN. Combined with outstanding infrastructure to collect detailed information through exploitation of the EMR and Data Warehouse, the partnership of the Personalized Medicine program, and involvement of a multi-disciplinary team across the institution and its affiliates, we bring tremendous manpower to bear upon this urgent problem.