Investigating the role of frailty on outcomes in acutely ill patients with cirrhosis undergoing liver transplantation in the acute care setting

PROJECT SUMMARY For patients with cirrhosis, liver transplantation is a well-established therapy, restoring liver function and reversing portal hypertension within days to weeks of the surgery itself. But cirrhosis also leads to insidious extra-hepatic effects such as muscle wasting, malnutrition, and functional impairment that may take months to reverse, if at all, which can compromise health and wellbeing (“global functional health”) after transplantation. In the ambulatory setting, these chronic cirrhosis manifestations can be captured by measures of “frailty”, the chronic biological state of decreased physiological reserve and increased vulnerability to health stressors, and operationalized using the Liver Frailty Index (LFI)—which our team developed from grip strength, chair stands, and balance. When assessed in the ambulatory setting, LFI predicts adverse health outcomes including hospitalizations and mortality. Frailty is now a well-accepted construct in hepatology/transplantation: in 2019, the American Society of Transplantation (AST) endorsed the use of standardized frailty metrics, including the LFI, for ambulatory liver transplant evaluation. However, approximately 1/3 of cirrhosis patients are hospitalized with acute illness immediately prior to transplant, in whom pre-morbid, ambulatory, frailty metrics may not be available. In this setting, transplant clinicians have, in many instances, been applying this construct in the acute care setting to inform transplant decisions—often informally through an “eyeball test”—despite a lack of studies evaluating the construct of frailty or tools to measure frailty in acutely ill patients. Unlike in the ambulatory setting where frailty represents factors that would not reverse with liver transplantation, a single frailty assessment in the acute setting may simply reflect the severity of acute liver-related decompensation, which, in theory, could reverse with a new liver. On the other hand, frailty trajectories may be informative of a patient’s ability to recovery a major stressor such as transplant surgery, so application of frailty as a trajectory may be more clinically appropriate. But testing of these hypotheses has not yet been done. In this proposal, we will leverage our 9-center research network to develop and validate a novel inpatient frailty index optimized for this acutely ill population, investigate models incorporating single and longitudinal assessments of frailty for the prediction of 1-year post-transplant global functional health, and associate inpatient frailty assessments with 1- year post-transplant healthcare utilization. Impact: Our proposal will result in a pragmatic, objective tool to standardize assessment of frailty in acutely ill patients with cirrhosis undergoing liver transplantation and clinical prediction models to guide use of single and longitudinal assessments of frailty for transplant decision- making in this clinically dynamic population. Understanding the precise relationship between acute care frailty and outcomes is essential to facilitate appropriate and systematic implementation of frailty in transplantation.