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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG048337-05
Application #
9521840
Study Section
Special Emphasis Panel (ZAG1)
Program Officer
Zieman, Susan
Project Start
2014-09-15
Project End
2019-04-30
Budget Start
2018-06-01
Budget End
2019-04-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Sinclair, Marie; Poltavskiy, Eduard; Dodge, Jennifer L et al. (2017) Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist. World J Gastroenterol 23:899-905
Lai, Jennifer C; Covinsky, Kenneth E; Dodge, Jennifer L et al. (2017) Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology 66:564-574
Carey, Elizabeth J; Lai, Jennifer C; Wang, Connie W et al. (2017) A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl 23:625-633
Puchades, Lorena; Chau, Stephanie; Dodson, John A et al. (2017) Association of Cardiac Abnormalities to the Frail Phenotype in Cirrhotic Patients on the Waitlist: From the Functional Assessment in Liver Transplantation (FrAILT) Study. Transplantation :
Spengler, Erin K; O'Leary, Jacqueline G; Te, Helen S et al. (2017) Liver Transplantation in the Obese Cirrhotic Patient. Transplantation 101:2288-2296
Kuo, Selena Z; Haftek, Marta; Lai, Jennifer C (2017) Factors Associated with Medication Non-adherence in Patients with End-Stage Liver Disease. Dig Dis Sci 62:543-549
Salazar, James; Saxena, Varun; Kahn, James G et al. (2017) Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C-Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma. Transplantation 101:1001-1008
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; Covinsky, Kenneth E; Hayssen, Hilary et al. (2016) Response to clinical assessments of health status as a potential marker to identify patients who are too sick to undergo transplantation. Liver Int 36:611
Kathpalia, Priya; Smith, Alexander; Lai, Jennifer C (2016) Underutilization of palliative care services in the liver transplant population. World J Transplant 6:594-8

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