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6,000名患者接受肝移植，而大约2,000人因死亡或临床恶化而从等待名单中删除。这2，000名患者是每年估计死于ESLD并发症的30，000人中的一小部分26，这表明肝脏的稀缺可能导致潜在的大量ESLD患者永远不会被列入等待名单。 事实上，现有的少数研究估计，只有不到5%的潜在移植候选人等待移植。27，28关于影响ESLD患者人群中谁被列为移植的因素的数据非常有限，几乎没有任何数据是基于人群的。一些因素，如性别和ESLD的原因可以在当地环境中进行研究。 然而，由于缺乏具有全国代表性的基于人群的数据，无法深入评价系统性因素（如供需的地理差异）如何影响ESLD患者的列名实践。因此，需要一种基于人口的方法来研究ESLD，以弥合这些未满足的知识差距。 该提案旨在建立这样一个基于人群的ESLD数据集，并利用这一新资源来检验核心假设，即传统研究仅关注肝移植患者，未能捕捉到上市实践和分配政策的真正影响。这项工作可以改变未来ESLD和移植结果研究的范式，以涵盖政策和实践对人口水平的影响。 这项工作将：a）采用两种新的算法来生成用于当前和未来ESLD结局研究的全国ESLD患者队列1，10~ B）识别潜在的可修改因素 (e.g.列出实践），可以改善所有潜在移植候选人的移植和结果，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，以促进他成为专注于改善ESLD患者结果的领先医生-科学家的目标。 具体目标是：1）确定与ESLD患者中肝移植登记相关的患者和地理因素~ 2）评价当地肝脏供需不匹配的总体影响~ 3）检查肝移植登记率如何影响等待登记患者和所有当地ESLD患者的不良患者结局。在宾夕法尼亚大学和临床中心流行病学和生物统计学的研究结构，通过医学佩雷尔曼学校在宾夕法尼亚大学提供的教学课程的补充提供了最佳的环境中，候选人将完成这项工作，并促进他的职业生涯作为一个临床医生和独立调查员。 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导师团队，以及一个具有长期研究和导师记录的咨询委员会。

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.