Global Functional Status in the Older Liver Transplant Candidate

描述(申请人提供)：肝移植是一种成熟的终末期肝病患者的治疗方法，目前有近16,000人在美国肝移植等待名单上。新登记的60岁患者的比例每年都在增加，与年轻患者相比，年龄较大的肝硬变患者由于合并疾病和功能损害的比率较高，因此面临更高的不良健康后果风险。然而，目前的国家肝脏分配政策要求，肝移植候补名单的优先顺序应纯粹基于他们在没有移植的情况下90天死亡的风险--与年龄无关--由终末期肝病评分模型确定，这是根据三种常见实验室测试计算的客观指标。但这一基于实验室的评分没有捕捉到的是功能状态恶化和渐进性医疗合并症等因素的综合影响，以及潜在的协同效应，这些因素可能会使年长的候选人在等待名单上特别容易死亡。在老年医学中， 对健康应激源的脆弱性已被概念化为患者的整体功能状态 并使用简单、有效的措施来预测社区老年人的不良健康后果，包括死亡率，这些措施往往比传统上单独使用的风险指标更好地进行操作。这项建议的主要目标是：1)建立功能衰退的比率，2)比较功能衰退与肝病进展之间的相关性，3)探讨老年(60岁)与年轻(46-55岁)等待肝移植的终末期肝病患者的年龄、功能衰退和死亡之间的关系。我假设，年龄较大的候选人会经历更快的功能衰退，这种快速衰退与死亡率的增加有关。这项研究将为肝移植社区提供所需的工具，以客观和更准确地评估与衰老相关的过程对老年肝移植候选患者结局的影响，老年肝移植候选患者是最有可能出现不良健康后果的患者亚群。将我的研究重点放在衰老过程上，因为它与老年肝移植候选人的等待名单死亡率有关，这将使我成为衰老相关研究和移植肝病学交叉领域的领先研究员。这些试点数据将作为未来研究的基础，以确定与老年候选人等待名单上的脆弱性或健壮性相关的老龄化相关因素，并开发包括功能状态衡量在内的等待名单死亡率预测模型。

DESCRIPTION (provided by applicant): Liver transplantation is a well-established therapy for patients with end-stage liver disease, with nearly 16,000 individuals currently on the U.S. liver transplant wait-list. The proportion of new listings ¿60 years of age has been increasing annually, and older, compared to younger, cirrhotic patients are at increased risk for adverse health outcomes due to higher rates of co-morbid conditions and functional impairment. However, current national liver allocation policy mandates that prioritization of wait-list candidates for liver transplantation should be based purely on their risk of 90-day mortality in th absence of transplantation - independent of age - as determined by the Model for End-Stage Liver Disease score, an objective metric calculated from three common laboratory tests. But what this laboratory-based score does not capture is the combined, and potentially synergistic, effect of factors such as deteriorating functional status and progressive medical co- morbidities that may make the older candidate particularly vulnerable to death on the wait-list. In Geriatrics, vulnerability to health stressors has been conceptualized as the patient's global functional status and operationalized using simple, validated measures that predict adverse health outcomes, including mortality, in community-dwelling elderly often better than traditionally used risk indice alone. The broad goal of this proposal is to: 1) establish the rate of functional decline, 2) compare the correlation between functional decline and liver disease progression, and 3) explore the association between age, functional decline, and death on the wait-list in older (¿60 years) compared to younger (46-55 years) patients with end-stage liver disease awaiting liver transplantation. I hypothesize that older candidates experience more rapid functional decline and that this rapid decline is associated with increased rates of death. This study will provide th liver transplant community with the tools needed to objectively and more accurately evaluate the impact of aging-related processes on the outcomes of older liver transplant candidates, the subgroup of patients who are at greatest risk for adverse health outcomes. Focusing my research on the aging process as it relates to wait-list mortality in older liver transplant candidates will position me to become a leading investigator at the intersection of aging-related research and transplant hepatology. These pilot data will serve as the foundation for future studies to identify aging-related factors associated with vulnerability - or robustness - on the wait-list in older candidates and develop a predictive model for wait-list mortality including measures of functional status.