Frailty 1 year after liver transplant is associated with long-term mortality: From the Functional Assessment in Liver Transplantation (FrAILT) Study

Frailty before liver transplantation (LT) is a critical determinant of outcomes after LT. While frailty often improves after LT, it persists-and even worsens-in some. The extent to which post-LT frailty impacts longer-term outcomes has not been characterized. Adults with cirrhosis who underwent LT between 2013-2023 from 9 centers with an ambulatory frailty assessment [by Liver Frailty Index (LFI)] 12 months (+/- 6 mo) post-LT were included. Kaplan-Meier methods were used to estimate post-LT survival beyond 1y post-LT. Associations between 1y post-LT frailty and subsequent mortality were assessed using Cox regression. Linear regression was used to explore the association between 1y post-LT frailty and health-related quality life (HrQOL) using the 36-Item Short Form Survey. Among 1097 LT recipients, 144 (13%) patients were frail 1y post-LT. Those who were frail 1y post-LT were more often women (47% vs 33%), had MASLD (40% vs 19%), diabetes (44% vs 30%), stroke (3.5% vs 0.6%), and pre-LT frailty (37% vs. 16%) (all p≤0.001). At 3, 5, and 7 years after the 1y post-LT assessment, mortality was higher among those who were frail vs. not frail 1y post-LT (13% vs 6%, 24% vs 10%, and 32% vs 16%). After multivariate adjustment, 1y post-LT frailty was associated 2.0 times increased risk of post-LT mortality (95%CI 1.2-3.4, p=0.01) and worse physical HrQOL (Estimate -9.99, 95%CI -12.5 to -7.5, p<0.001). Patients who were frail 1y after LT experienced >2-fold increased risk of long-term mortality and poorer physical HrQOL. Patients who transitioned from not frail pre-LT to frail 1y post-LT had a 2.5-fold increased risk of post-LT mortality (95%CI 1.3-4.8, p=0.005) compared to patients who remained not frail. These findings suggest the 1y period after LT may be a critical window for evaluating whether targeted frailty-mitigation strategies may improving long-term survival among LT recipients.