The Impact of Frailty on Liver Transplant Outcomes in Older Adults with Hepatocellular Carcinoma

项目摘要 我是一名移植肝病专家，在消化内科担任副教授。 和肝病，他已经开发了一个国家认可的临床研究计划，专注于这种应用 老年研究和老年护理原则对等待和治疗肝硬变患者的管理 正在接受肝移植的患者。支持我目前的活动，包括老龄化研究和指导 包括不同的资源库：1)NIA R01，以了解脆弱性在全球功能健康中的作用 肝移植后的患者，2)NIA R21为肝硬变患者开发实验室脆弱指数， 3)肝移植中认知损害和阿尔茨海默病危险因素的NIA补充研究 接受者，4)几项由行业支持的调查者发起的研究，以评估与老龄化相关的因素 肝硬变患者，5)慈善支持的慢性肝病患者的研究，6)捐赠的 教授职位。我的研究资助充分利用了肝脏功能评估的数据和基础设施 移植(FrAILT)研究，我于2012年创立，目前是全球最大的专门研究队列 为了研究衰老--既包括时间上的(即年龄)，也包括生理上的(即虚弱)--对儿童预后的影响 患有肝硬变的病人。对于本K24中提出的新研究，我将把我的研究计划扩展到更老的 通过丰富我们现有的数据来确定符合肝移植条件的成年肝细胞癌患者 使用细粒度的肝细胞癌指标和其他与年龄相关的指标：通过以下方式表征不同的患者群体 脆弱轨迹和识别脆弱轨迹组成员的新预测因子(目标1)，并调查 脆弱轨迹与等待名单退出(AIM 2)或移植后整体功能健康之间的关联 (目标3)。在此过程中，我将创建一个代表美国肝细胞癌人群的唯一多中心数据集 结合了衰老、肝脏、肝细胞癌和移植相关的因素，这不仅将扩大我的研究组合 也使我能够培训新的导师，他们有兴趣从事以患者为中心的研究 衰老研究、肝病学、肿瘤学和移植。这项科学提案利用了我目前的技能， 临床和研究知识，以及我现有的团队为我提供了开发新研究的机会 在等待和接受肝移植的老年肝癌患者中，这一研究不足的人群的技能和方法 移植。在K24期间，我计划在专业领导力和指导技能方面进行额外的培训 发展，并将为我的导师创建一个正式的研究/职业课程，以确保一个有组织的和 未来几年可持续的指导计划。考虑到我自己的职业生涯，我是一名医学专家(肝病) 在一个以外科手术为导向的学科(移植)中，得到了来自 在老年医学和老龄化研究社区，我特别适合为学员和早期阶段提供支持 内科和外科分专业的研究人员谁可以进一步促进老龄化研究和老年医学 在他们的专科范围内的护理原则。

PROJECT ABSTRACT I am a transplant hepatologist on faculty as Associate Professor of Medicine in the Division of Gastroenterology & Hepatology, who has developed a nationally recognized clinical research program focused on the application of aging research and geriatric principles of care to the management of patients with cirrhosis awaiting and undergoing liver transplantation. Support for my current activities involving aging research and mentorship include a diverse pool of resources: 1) a NIA R01 to understand the role of frailty on global functional health in patients after liver transplantation, 2) a NIA R21 to develop a laboratory frailty index for patients with cirrhosis, 3) a NIA supplement to characterize cognitive impairment and Alzheimers Disease risk factors in liver transplant recipients, 4) several industry-supported investigator-initiated studies to evaluate aging-related factors in cirrhosis patients, 5) philanthropy-supported research in patients with chronic liver disease, and 6) an endowed professorship. My research grants leverage the data and infrastructure of the Functional Assessment in Liver Transplantation (FrAILT) Study, which I founded in 2012 and is currently the largest cohort worldwide dedicated to investigating the effect of aging—both chronologic (i.e., age) and physiologic (i.e., frailty)—on outcomes in patients with cirrhosis. For the new research proposed in this K24, I will expand my research program to older adults with hepatocellular carcinoma (HCC) who are eligible for liver transplantation by enriching our current data with granular HCC metrics and additional aging-related metrics to: characterize distinct groups of patients by frailty trajectories and identify novel predictors of frailty trajectory group membership (Aim 1), and investigate the association between frailty trajectories and waitlist dropout (Aim 2) or post-transplant global functional health (Aim 3). In so doing, I will create a unique multi-center dataset that is representative of the U.S. HCC population and combines aging-, liver-, HCC-, and transplant-related factors that will not only expand my research portfolio but also enable me to train new mentees interested in pursuing patient-oriented research at the intersection of aging research, hepatology, oncology, and transplantation. This scientific proposal leverages my current skills, clinical and research knowledge, and my established cohort to offer me the opportunity to develop new research skills and approaches in this under-studied population of older adults with HCC awaiting and undergoing liver transplantation. During this K24, I plan additional training in professional leadership and mentorship skills development, and will create for my mentees a formal research/career curriculum to ensure a structured and sustainable mentoring program for years to come. Given my own career as a medical subspecialist (hepatology) in a surgically-oriented discipline (transplant) with long-standing intellectual and financial support from the geriatric and aging research communities, I am particularly well-positioned to support trainees and early stage investigators in medical and surgical subspecialties who can further promote aging research and geriatric principles of care within their subspecialities.