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

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PROJECT SUMMARY Cirrhosis leads to the insidious effects of muscle wasting and malnutrition that have come to be known in the hepatology community as “frailty”, adapting the geriatric construct of a state of decreased physiological reserve and increased vulnerability to stressors. We developed the novel Liver Frailty Index (LFI) using tests of physical function (grip strength, chair stands, balance) in 2017 to standardize assessment of frailty in patients with cirrhosis and demonstrated its value in predicting adverse outcomes including death, healthcare utilization, and disability. Since its development, many hepatology/ transplant centers globally have adopted the LFI in their in-person evaluations of liver transplant patients. National guidelines by the American Society of Transplantation (2019) and American Association for the Study of Liver Diseases have formally endorsed routine frailty assessment in cirrhosis patients using standardized metrics, such as the LFI. But in the face of the coronavirus disease 2019 (COVID-19) pandemic, the clinical landscape shifted dramatically from in-person visits to telemedicine. Use of telemedicine increased by 4000% among patients with chronic liver diseases within the first 2 weeks of the pandemic, with 98% of U.S. liver transplant programs reporting using telemedicine for all phases of transplant care. Telemedicine has proven to be highly acceptable by both patients and clinicians, suggesting that even as in-person visits resume with control of the pandemic, telemedicine will continue to complement—if not dominate—in-person care provided in hepatology. This raises a new (and unforeseen) unmet need in transplant practice for the development of standardized frailty tools to capture the frailty construct in patients with cirrhosis that can be administered entirely virtually. In this application, we aim to address this unmet need by deriving a novel composite index that can be administered entirely virtually, called the “TeLeFI”, and evaluate the association between the TeLeFI and clinical outcomes including hospitalizations and waitlist mortality. We will leverage our multi-center Functional Assessment in Liver Transplantation (FrAILT) Study infrastructure to assess frailty and frailty-related components (e.g., physical function, performance status, disability) virtually using a battery of established instruments that can then be evaluated for inclusion in the TeLeFI. This objective fits squarely within the original scope of the parent award (R01 AG059183), which is to investigate the association between frailty and transplant-related outcomes in patients with cirrhosis, but will achieve a new research objective to derive this virtual frailty assessment tool. These aims will serve as the foundation for a subsequent R01 proposal to: 1) validate the TeLeFI for the prediction of waitlist outcomes in an adequately powered cohort (using our existing multi-center FrAILT Study infrastructure) and 2) investigate the association between TeLeFI and outcomes after liver transplantation.