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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Kuo, Selena Z; Haftek, Marta; Lai, Jennifer C (2016) Factors Associated with Medication Non-adherence in Patients with End-Stage Liver Disease. Dig Dis Sci :
Wang, Connie W; Feng, Sandy; Covinsky, Kenneth E et al. (2016) A Comparison of Muscle Function, Mass, and Quality in Liver Transplant Candidates: Results From the Functional Assessment in Liver Transplantation Study. Transplantation 100:1692-8
Salazar, James; Saxena, Varun; Kahn, James G et al. (2016) Cost-Effectiveness of Direct-Acting Anti-viral Treatment in Hepatitis C-infected Liver Transplant Candidates with Compensated Cirrhosis and Hepatocellular Carcinoma. Transplantation :
Samoylova, Mariya L; Covinsky, Kenneth E; Haftek, Marta et al. (2016) Disability in Patients with End-Stage Liver Disease: Results from the Functional Assessment in Liver Transplantation (FrAILT) Study. Liver Transpl :
Lai, Jennifer C (2016) Defining the threshold for too sick for transplant. Curr Opin Organ Transplant 21:127-32
Pavasini, Rita; Guralnik, Jack; Brown, Justin C et al. (2016) Short Physical Performance Battery and all-cause mortality: systematic review and meta-analysis. BMC Med 14:215
Lai, Jennifer C; Volk, Michael L; Strasburg, Debra et al. (2016) Performance-Based Measures Associate With Frailty in Patients With End-Stage Liver Disease. Transplantation 100:2656-2660
Lai, Jennifer C; Dodge, Jennifer L; Sen, Saunak et al. (2016) Functional decline in patients with cirrhosis awaiting liver transplantation: Results from the functional assessment in liver transplantation (FrAILT) study. Hepatology 63:574-80
Wang, Connie W; Covinsky, Kenneth E; Feng, Sandy et al. (2015) Functional impairment in older liver transplantation candidates: From the functional assessment in liver transplantation study. Liver Transpl 21:1465-70
Saxena, Varun; Lai, Jennifer C (2015) Kidney Failure and Liver Allocation: Current Practices and Potential Improvements. Adv Chronic Kidney Dis 22:391-8

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