Changes in frailty are associated with waitlist mortality in patients with cirrhosis.

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Frailty is predictive of death in patients with cirrhosis, but studies to date have been limited to assessments at a single time point. We aimed to evaluate changes in frailty over time (ΔLFI) and its association with death/delisting for sickness.Adults with cirrhosis listed for liver transplantation without hepatocellular carcinoma at 8 U.S. centers underwent ambulatory longitudinal frailty testing with the Liver Frailty Index (LFI). We used multilevel linear mixed effects regression to model and predict ΔLFI per 3 months based on age, gender, MELDNa, ascites, and hepatic encephalopathy (HE) and categorize patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk.We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe frailty worsening had worse baseline LFI and were more likely to have NAFLD, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted for sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELDNa, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI, 1.35-3.09).Changes in frailty were significantly associated with death/delisting independent of baseline frailty and MELDNa. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting than those who experienced worsening frailty. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.


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