Older patients with cirrhosis are at high risk for adverse health outcomes due to the combined, and potentially synergistic, effects of chronic liver failure and aging processes. While the proportion of older patients with end-stage liver disease considering liver transplantation is rapidly escalating, transplant clinicians lack tools t objectively measure the impact of the aging-related factors of frailty and functional status on transplant outcomes. To address this knowledge gap, I have outlined 3 research aims in this proposal. Leveraging my ongoing prospective cohort study of patients with end-stage liver disease e60 years old awaiting liver transplantation, I will: (1) associate pre-transplant measures of frailty and functional status with outcomes within 2 years of transplant (Aim 1) and (2) characterize frailty and functional status at 3, 6, and 12 months after transplant (Aim 2). Utilizig a consortium of U.S. liver transplant centers that I have established during my fellowship, I will test the feasibility of administering these measures of frailty and functional status in a pilot cohort of 120 liver transplant candidates ?60 years old at 3 other U.S. transplant centers (Aim 3). I am a hepatologist specializing in liver transplantation at the University of California, San Francisco. Building upon a strong foundation of aging research support [NIA GEMSSTAR, T. Franklin Williams Scholar Award, and a UCSF Older Americans Independence Center (OAIC) Pilot Award], this Paul B. Beeson Career Development Award in Aging will establish me as an independent clinical investigator pioneering research at the intersection of aging, hepatology, and transplant disciplines. Under the direct supervision of a multidisciplinary team of leaders in geriatrics (Covinsky), hepatology (Terrault), transplant surgery (Feng, Segev), and biostatistics (Boscardin), I will execute a detailed career development plan to accelerate my path toward 4 key career goals outlined in this proposal: (1) to develop a foundation of core gerontologic principles; (2) to acquire analytic skills for longitudinal cohort studies; (3) to gain skills in mlti-center collaboration; (4) to cultivate leadership skills for national efforts to integrate geriatri constructs into the care of older patients with cirrhosis and their selection for liver transplantation. As part of my 5-year plan, I will actively engage in coursework and structured tutorials in aging and biostatistics as well as interdisciplinary career development and leadership programs. In addition, through the UCSF Division of Geriatrics, UCSF OAIC, and national geriatrics conferences including the Beeson meeting, I will integrate myself into the aging research community and establish a network of aging researchers for current and future collaboration.

Public Health Relevance

Characterizing frailty and functional status and its association with outcomes in the liver transplant setting can elucidate those who will achieve acceptable transplant outcomes and compel equitable access to transplant in select older cirrhotics. This proposal lays the groundwork for an R01 to incorporate geriatric assessments into the routine evaluation of all older patients with end-stage liver disease.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Zieman, Susan
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
United States
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Cullaro, Giuseppe; Park, Meyeon; Lai, Jennifer C (2018) ""Normal"" Creatinine Levels Predict Persistent Kidney Injury and Waitlist Mortality in Outpatients With Cirrhosis. Hepatology 68:1953-1960
Perito, Emily R; Bucuvalas, John; Lai, Jennifer C (2018) Functional status at listing predicts waitlist and posttransplant mortality in pediatric liver transplant candidates. Am J Transplant :
Lai, Jennifer C; Segev, Dorry L; McCulloch, Charles E et al. (2018) Physical frailty after liver transplantation. Am J Transplant 18:1986-1994
Cullaro, Giuseppe; Sarkar, Monika; Lai, Jennifer C (2018) Sex-based disparities in delisting for being ""too sick"" for liver transplantation. Am J Transplant 18:1214-1219
Chascsa, David M; Lai, Jennifer C; Dunn, Michael A et al. (2018) Patient and Caregiver Attitudes and Practices of Exercise in Candidates Listed for Liver Transplantation. Dig Dis Sci 63:3290-3296
Kobashigawa, Jon; Dadhania, Darshana; Bhorade, Sangeeta et al. (2018) Report from the American Society of Transplantation on frailty in solid organ transplantation. Am J Transplant :
Cullaro, Giuseppe; Hirose, Ryutaro; Lai, Jennifer C (2018) Changes in Simultaneous Liver Kidney Transplant Allocation Policy May Impact Post Liver Transplant Outcomes. Transplantation :
Puchades, Lorena; Chau, Stephanie; Dodson, John A et al. (2018) Association of Cardiac Abnormalities to the Frail Phenotype in Cirrhotic Patients on the Waitlist: From the Functional Assessment in Liver Transplantation Study. Transplantation 102:e101-e107
Lai, Jennifer C; Covinsky, Kenneth E; McCulloch, Charles E et al. (2018) The Liver Frailty Index Improves Mortality Prediction of the Subjective Clinician Assessment in Patients With Cirrhosis. Am J Gastroenterol 113:235-242
Hsu, Evelyn K; Shaffer, Michele L; Gao, Lucy et al. (2017) Analysis of Liver Offers to Pediatric Candidates on the Transplant Wait List. Gastroenterology 153:988-995

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