A population-based cohort to study outcomes in end-stage liver disease patients

项目摘要/摘要 虽然肝移植是终末期肝病(ESLD)患者的救命手段，但缺乏 身体肝脏限制了其对公共健康的影响。每年大约有6,000名患者接受肝脏 在美国，大约有2000人因死亡或临床原因而被从等待名单中删除 这2,000名患者只占每年估计的30,000人死亡人数的一小部分 来自ESLD26的并发症，表明肝脏的稀缺可能导致大量的ESLD 病人永远不会被列入等待名单。事实上，为数不多的现有研究估计，只有不到5%的潜在 移植候选人永远都在等待。27，28关于影响移植患者的因素的数据非常有限 ESLD患者的人口被列入移植名单，几乎没有一个数据是人口- 基于。一些因素，如性别和ESLD的原因，可以在当地环境中进行研究。然而， 缺乏具有全国代表性的以人口为基础的数据，阻碍了对 系统性因素，如供需的地理差异，影响ESLD的上市做法 病人。因此，需要一种基于人群的方法来研究ESLD，以弥合这些未满足的知识 差距。这项建议旨在建立这样一个基于人口的ESLD数据集，并使用这一新资源 为了验证这一中心假设，传统研究只关注肝移植患者， 未能捕捉到上市做法和分配政策的真正影响。这项工作可以通过以下方式改变这一范式 进行了哪些未来的ESLD和移植结果研究，以涵盖人口层面的影响 政策和做法。这项工作将：a)使用两种新的算法来生成ESLD的全国队列 用于目前和未来ESLD结果研究的患者1，10~b)确定潜在的可修改因素 (例如，列出可改善所有潜在移植中的移植机会和结果的做法) 考生~和c)教申请者使用几种新的流行病学和人口学方法 他的目标是成为一名领先的内科科学家，专注于改善ESLD患者的预后。这个 具体目标是：1)确定与列入移植名单相关的患者和地理因素 ESLD患者~2)评估肝脏供需局部不匹配的总体影响~和3) 检查两个候补名单中肝移植的上市率如何影响患者的不良结局 患者和所有局部ESLD患者。宾夕法尼亚大学的研究结构与临床 流行病学和生物统计中心，辅以通过 宾夕法尼亚大学佩雷尔曼医学院提供了最佳环境， 候选人将完成这项工作，并促进他的职业生涯作为临床医生和独立调查员。Dr。 Goldberg组建了一支具有流行病学、卫生服务和肝病专业知识的导师团队。 此外，还有一个长期从事研究和指导工作的咨询委员会。

Project Summary/Abstract Although liver transplantation is lifesaving for patients with end-stage liver disease (ESLD), the scarcity of cadaveric livers constrains its public health impact. Each year, approximately 6,000 patients undergo liver transplantation in the U.S., while roughly 2,000 are removed from the waitlist due to death or clinical deterioration.25 These 2,000 patients are a small fraction of the estimated 30,000 people that die each year from complications of ESLD26, suggesting the scarcity of livers may cause a potentially large number of ESLD patients to never be waitlisted. Indeed, the few available studies have estimated that less than 5% of potential transplant candidates are ever waitlisted.27,28 There are very limited data on factors that influence who among the population of patients with ESLD is listed for transplantation, and almost none of the data are population- based. Some factors, such as gender and cause of ESLD can be studied in local settings. However, the absence of nationally representative population-based data has prevented an in-depth evaluation of how systemic factors, such as geographic variations in supply and demand influence listing practices for ESLD patients. Thus, a population-based approach to studying ESLD is needed to bridge these unmet knowledge gaps. This proposal aims to establish such a population-based dataset of ESLD, and to use this new resource to test the central hypothesis that traditional research, focusing only on patients listed for liver transplantation, fails to capture the true impact of listing practices and allocation policies. The work could shift the paradigm by which future ESLD and transplant outcomes research is conducted to encompass population-level impacts of policies and practices. This work will: a) employ two novel algorithms to generate a national cohort of ESLD patients to be used for present and future ESLD outcomes research1,10~ b) identify potentially modifiable factors (e.g. listing practices) that can improve access to transplantation and outcomes among all potential transplant candidates~ and c) teach the applicant to use several new epidemiologic and demographic methods to foster his goal of become a leading physician-scientist focused on improving outcomes for ESLD patients. The specific aims are to: 1) identify patient and geographic factors associated with listing for transplantation among ESLD patients~ 2) evaluate the total impact of local mismatches between liver supply and demand~ and 3) examine how rates of listing for liver transplantation influence adverse patient outcomes among both waitlisted patients and all local ESLD patients. The research structure at the University of Pennsylvania and the Clinical Center for Epidemiology and Biostatistics, supplemented by the didactic coursework offered through the Perelman School of Medicine at the University of Pennsylvania offer the optimal environment within which the candidate will complete this work and foster his career as a clinician and independent investigator. Dr. Goldberg has assembled a mentorship team with expertise in epidemiologic, health services, and hepatology research, and an Advisory Committee with a longstanding track record of research and mentorship.