Predicting post-transplant mortality and global functional health based on pre-transplant functional status in liver transplantation

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PROJECT SUMMARY The decision to proceed with liver transplantation in a patient with end-stage liver disease depends not just on the risk of death without transplant but the risk of adverse outcomes after it. The transplant clinician's assess- ment of a cirrhotic patient's global functional health – which we have conceptualized as his or her vulnerability to health stressors – is a critical factor (oftentimes the sole factor) in this decision. Yet at the current time, no standardized, objective criteria for poor global functional health exist to define who is “too frail for transplant”. Rather, assessment of functional status in transplant is subjective and is applied to decision-making ad hoc, resulting in unequal transplant access and potential denial of otherwise suitable candidates. To facilitate transplant decision-making, a precise understanding of how pre-transplant functional status impacts post- transplant outcomes is needed to inform prediction of who will not regain excellent global functional health after transplant. We have demonstrated that tools to quantify frailty and functional status in older adults have proven valuable to measure global functional health in cirrhotic patients and have developed an objective Liver Frailty Index, consisting of a composite of performance-based tests (grip strength, chairs stands, and balance testing), to capture longitudinal changes in functional status specifically for use in the pre- and post-transplant settings. Building logically upon this work, we propose to determine the impact of pre-transplant functional status on 1-year post-transplant mortality and global functional health and develop/validate clinical prediction rules for these outcomes that incorporate pre-transplant functional status. To accomplish these goals, we will leverage our existing Multi-center Functional Assessment in Liver Transplantation Study, consisting of 5 US liver transplant centers (UCSF, Johns Hopkins, Columbia, Baylor, and Duke) with a track record of collaboration and high-impact research to obtain data on a minimum of 1,300 liver transplant recipients with assessments of functional status pre-transplantation and assessments of global functional health (including the Liver Frailty Index, disability, and quality of life) 1-year post-transplantation. These data will be used to develop and validate clinical prediction rules that incorporate both pre-transplant functional status, patient and donor characteristics to predict death, functional status, disability, and quality of life 1-year after transplantation. This project will positively impact the field by expanding our ability to measure the benefit of transplant both by how long a recipient will live as well as by how well a recipient will live after liver transplantation. Importantly, this project will facilitate clinical decision-making for patients and their clinicians through the precise understanding of how functional status impacts outcomes and what patients can expect after liver transplantation with respect to functional recovery. Given that functional status is modifiable in cirrhotic patients, our data will also support future investigations to develop effective strategies to improve pre-transplant functional status with the goal of reducing mortality and optimizing post-transplant functional health.