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

虚弱对老年肝细胞癌肝移植结果的影响

• 批准号: 10570786
• 负责人: Jennifer C. Lai
• 金额: $ 18.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570786
• 关键词: Acceleration; Accounting; Adipose tissue; Age; Aging; Alzheimer' s disease risk; Award; Cancer Etiology; Caring; Categories; Cessation of life; Chronic; Chronology; Cirrhosis; Classification; Clinical; Clinical Research; Communities; Data; Data Set; Databases; Decision Making; Dedications; Discipline; Disease; Dropout; Educational Curriculum; Elderly; Eligibility Determination; Endowment; Ensure; Exclusion; Faculty; Financial Support; Funding; Gastroenterology; Geriatrics; Habilitation; Health; Hepatology; Hospitalization; Impaired cognition; Improve Access; Industry; Infrastructure; Intervention; Intuition; Knowledge; Laboratories; Leadership; Liver; Liver Failure; Liver diseases; Living Donor Liver Transplantation; MRI Scans; Measurement; Medical; Medicine; Mentors; Mentorship; Modeling; Muscle; Natural History; Older Population; Oncology; Operative Surgical Procedures; Organ; Organ Transplantation; Outcome; Pathway interactions; Patients; Pattern; Perioperative; Physiological; Population; Positioning Attribute; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Quality of life; Recurrence; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Risk Assessment; Risk Factors; Role; Severity of illness; Skeletal Muscle; Solid; Stage at Diagnosis; Standardization; Structure; Surgical Specialties; Testing; Time; Training; Transplant Recipients; Transplantation; Tumor Burden; Waiting Lists; Work; abdominal CT; age effect; aging demographic; aging demography; alpha-Fetoproteins; career; career development; chronic liver disease; cohort; comorbidity; curative treatments; demographics; disability; experience; fitness; frailty; functional status; human old age (65+); improved; indexing; interest; liver function; liver transplantation; mid-career faculty; mortality; muscle form; next generation; novel; patient oriented; patient oriented research; post-transplant; prognostic; programs; skill acquisition; skills; transplant centers; tumor progression

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.

项目摘要 我是一名移植肝病学家，担任胃肠病学系医学副教授 和肝病学，开发了一个全国认可的临床研究项目，专注于该应用 老龄化研究和老年护理原则对等待和治疗的肝硬化患者的管理 支持我目前涉及衰老研究和指导的活动。 包括多种资源：1) NIA R01，用于了解虚弱对全球功能健康的作用 肝移植后的患者，2) NIA R21 为肝硬化患者制定实验室衰弱指数， 3) NIA 补充剂，用于表征移植肝中的认知障碍和阿尔茨海默病危险因素 接受者，4）几项由行业支持的研究者发起的研究，以评估衰老相关因素 肝硬化患者，5) 慈善事业支持的慢性肝病患者研究，以及 6) 捐赠 我的研究经费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 研究衰老（即年龄）和生理（即虚弱）对结果的影响 对于本 K24 中提出的新研究，我将把我的研究计划扩展到老年患者。 通过丰富我们当前的数据，有资格接受肝移植的肝细胞癌 (HCC) 成人患者 具有细化的 HCC 指标和其他与衰老相关的指标： 衰弱轨迹并确定衰弱轨迹组成员资格的新预测因子（目标 1），并研究 虚弱轨迹与候补名单退出（目标 2）或移植后全球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 HCC 人群的独特的多中心数据集。 并结合了衰老、肝脏、肝癌和移植相关因素，这不仅扩大了我的研究范围 但也使我能够培训有兴趣在交叉领域进行以患者为导向的研究的新学员 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的既定团队为我提供了开展新研究的机会 在等待和接受肝病治疗的患有 HCC 的老年人群体中的技能和方法尚未得到充分研究 在 K24 期间，我计划进行专业领导力和指导技能方面的额外培训。 发展，并将为我的学员创建正式的研究/职业课程，以确保结构化和 鉴于我自己作为医学专科医生（肝病学）的职业生涯，我将在未来几年内开展可持续的指导计划。 在以外科为导向的学科（移植）中，得到了来自以下机构的长期智力和财政支持 在老年医学和老龄化研究社区中，我特别适合支持受训者和早期阶段 医学和外科亚专业的研究人员可以进一步促进衰老研究和老年病学 其亚专业内的护理原则。