Liver transplantation is a well-established therapy for patients with end-stage liver disease, with nearly 16,000 individuals currently on the U.S. liver transplant wait-list. The proportion of new listings >=60 years of age has been increasing annually, and older, compared to younger, cirrhotic patients are at increased risk for adverse health outcomes due to higher rates of co-morbid conditions and functional impairment. However, current national liver allocation policy mandates that prioritization of wait-list candidates for liver transplantation should be based purely on their risk of 90-day mortality in th absence of transplantation - independent of age - as determined by the Model for End-Stage Liver Disease score, an objective metric calculated from three common laboratory tests. But what this laboratory-based score does not capture is the combined, and potentially synergistic, effect of factors such as deteriorating functional status and progressive medical co- morbidities that may make the older candidate particularly vulnerable to death on the wait-list. In Geriatrics, vulnerability to health stressors has been conceptualized as the patient's global functional status and operationalized using simple, validated measures that predict adverse health outcomes, including mortality, in community-dwelling elderly often better than traditionally used risk indice alone. The broad goal of this proposal is to: 1) establish the rate of functional decline, 2) compare the correlation between functional decline and liver disease progression, and 3) explore the association between age, functional decline, and death on the wait-list in older (?60 years) compared to younger (46-55 years) patients with end-stage liver disease awaiting liver transplantation. I hypothesize that older candidates experience more rapid functional decline and that this rapid decline is associated with increased rates of death. This study will provide th liver transplant community with the tools needed to objectively and more accurately evaluate the impact of aging-related processes on the outcomes of older liver transplant candidates, the subgroup of patients who are at greatest risk for adverse health outcomes. Focusing my research on the aging process as it relates to wait-list mortality in older liver transplant candidates will position me to become a leading investigator at the intersection of aging-related research and transplant hepatology. These pilot data will serve as the foundation for future studies to identify aging-related factors associated with vulnerability - or robustness - on the wait-list in older candidates and develop a predictive model for wait-list mortality including measures of functional status.

Public Health Relevance

A better understanding of the impact of functional decline on the older liver transplant candidate and the incorporation of its objective measurement into transplant decision-making has broad implications. It may lead to: 1) expanded access to liver transplantation to those are physiologically fit, regardless of chronologic age and 2) characterization of older candidates who would benefit from transplantation at an earlier stage in their liver disease progression.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Small Research Grants (R03)
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Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
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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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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
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
Samoylova, Mariya L; Covinsky, Kenneth E; Haftek, Marta et al. (2017) Disability in patients with end-stage liver disease: Results from the functional assessment in liver transplantation study. Liver Transpl 23:292-298
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
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
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
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; 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
Saxena, Varun; Lai, Jennifer C (2015) Kidney Failure and Liver Allocation: Current Practices and Potential Improvements. Adv Chronic Kidney Dis 22:391-8
Lai, Jennifer C; Covinsky, Kenneth E; Hayssen, Hilary et al. (2015) Clinician assessments of health status predict mortality in patients with end-stage liver disease awaiting liver transplantation. Liver Int 35:2167-73

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