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

描述（由申请人提供）：尽管肝移植可以挽救终末期肝病（ESLD）患者的生命，但尸体肝脏的稀缺限制了其对公共卫生的影响。在美国，每年大约有6000名患者接受肝移植，而大约有2000名患者因死亡或临床恶化而被从候补名单中除名。这2000名患者只占每年死于ESLD26并发症的约3万人的一小部分，这表明肝脏的稀缺可能导致潜在的大量ESLD患者从未被列入候补名单。事实上，为数不多的可用研究估计，只有不到5%的潜在移植候选者被列入候补名单影响ESLD患者中哪些人被列入移植名单的因素的数据非常有限，而且几乎没有数据是基于人群的。一些因素，如性别和ESLD的原因可以在当地进行研究。然而，由于缺乏具有全国代表性的人口数据，因此无法深入评估供需地理差异等系统性因素如何影响ESLD患者的列单做法。因此，需要一种基于人群的方法来研究ESLD，以弥合这些未被满足的知识差距。本提案旨在建立这样一个基于人群的ESLD数据集，并利用这一新的资源来检验一个中心假设，即传统研究只关注肝移植患者，未能捕捉到列表实践和分配政策的真正影响。这项工作可能会改变未来ESLD和移植结果研究的范式，使其涵盖政策和实践的人口水平影响。这项工作将：a)采用两种新颖的算法生成ESLD患者的全国队列，用于当前和未来的ESLD结果研究1,10~ b)确定潜在的可修改因素（例如列出实践），可以改善所有潜在移植候选人的移植机会和结果~以及c)教申请人使用几种新的流行病学和人口统计学方法，以实现他的目标，成为专注于改善ESLD结果的领先医师和科学家病人。具体目的是：1)确定与ESLD患者移植名单相关的患者和地理因素；2)评估当地肝脏供需不匹配的总体影响；3)检查肝移植名单率如何影响等待名单患者和所有当地ESLD患者的不良患者结局。宾夕法尼亚大学和流行病学和生物统计学临床中心的研究结构，辅以宾夕法尼亚大学佩雷尔曼医学院提供的教学课程，为候选人完成这项工作提供了最佳环境，并培养了他作为临床医生和独立研究者的职业生涯。Goldberg博士组建了一个具有流行病学、卫生服务和肝病学研究专业知识的指导团队，以及一个具有长期研究和指导记录的咨询委员会。

DESCRIPTION (provided by applicant): 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. 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 improv 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.