Liver Transplantation Provides Survival Benefit at All Levels of Frailty: from the Multicenter Functional Assessment in Liver Transplantation Study

Background & Aims: Offering LT to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. We sought to quantify net survival benefit with LT by liver frailty index (LFI). Approach & Results: We analyzed data in the multi-center Functional Assessment in LT (FrAILT) Study from 2012-2021. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without hepatocellular carcinoma; post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. We computed 1-, 3-, and 5-year restricted mean survival times (RMST) from adjusted Cox models. Survival benefit was calculated as net gain in life-years with LT. Pre-LT cohort included 2628 patients: median MELDNa was 18 (IQR 14-22); 731 (28%) were frail; 440 (17%) died pre-LT. Post-LT cohort included 1335 patients: median MELDNa was 20 (IQR 14-24); 325 (24%) were frail; 103 (8%) died post-LT. Pre-LT RMST decreased substantially as LFI increased. Post-LT RMST also decreased as LFI increased but only modestly. There was no LFI threshold at which pre-LT and post-LT RMST intersected-patients had net survival benefit at all LFI values. Conclusion: Pre-LT and, to a lesser degree, post-LT mortality increased as LFI increased. Transplant offered a survival benefit at all LFI values, driven by a reduction in pre-LT mortality. No threshold of LFI was identified at which the risk of post-LT mortality exceeded pre-LT mortality. LT offers net survival benefit even in the presence of advanced frailty among those selected for LT.