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

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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.