Global 
Deutschland Liver and Bile
Hepatology. 2025;81(4):1269-1275
Liver transplantation provides survival benefit at all levels of frailty: From the multicenter Functional Assessment in Liver Transplantation Study
Background and aims: Offering liver transplantation (LT) to frail patients may reduce waitlist mortality but may increase post-LT mortality. LT survival benefit is the concept of balancing these risks. The authors sought to quantify the net survival benefit with LT by liver frailty index (LFI).
Approach and results: Data in the multicenter Functional Assessment in LT (FrAILT) study from 2012 to 2021 were analyzed. Pre-LT cohort included ambulatory patients with cirrhosis awaiting LT, without hepatocellular carcinoma (HCC); the post-LT cohort included those who underwent LT. Primary outcomes were pre-LT and post-LT mortality. The authors computed 1-, 3-, and 5-year restricted mean survival times (RMSTs) from adjusted Cox models. The survival benefit was calculated as a net gain in life-years with LT. Pre-LT cohort included 2628 patients: median Model for End-Stage Liver Disease-Sodium (MELD-Na) was 18 (interquartile range [IQR], 14–22); 731 (28%) were frail; 440 (17%) died before LT. Post-LT cohort included 1335 patients: median MELD-Na was 20 (IQR, 14–24); 325 (24%) were frail; 103 (8%) died after 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 benefits at all LFI values.
Conclusions: Pre-liver transplantation (LT) and, to a lesser degree, post-LT mortality increased as liver frailty index (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 benefits even in the presence of advanced frailty among those selected for LT.
DOI: 10.1097/hep.0000000000001030
PD Dr. Michael Schultheiß
PD Dr. Michael Schultheiß, Head of the Interdisciplinary Ultrasound Center and Clinical Head of the TIPS Section, University Medical Center Freiburg, Department of Internal Medicine II, Hugstetter Str. 55, 79106 Freiburg, Germany
Frailty in liver cirrhosis: Have we underestimated it for too long?
The importance and clinical relevance of the study by Wang et al. cannot be overstated. Frailty, an established concept in geriatrics, is a factor that has not yet been sufficiently considered and is therefore clearly underestimated in the evaluation of patients with liver cirrhosis. Frailty could be particularly relevant in the context of liver transplantation (LT), as investigated in this study.
In this observational study, the authors analyzed survival data from 2628 outpatients listed for LT (pre-LT cohort). Of these patients, 28% met the criteria for frailty as defined by the Liver Frailty Index (LFI). In the cohort of 1335 patients examined after LT (post-LT cohort), 24% met the criteria for frailty.
The study results showed in particular that a high LFI in the pre-LT cohort was associated with a high mortality rate. Frailty after LT contributed significantly less to mortality. For example, a pre-LT LFI of 5.0 was associated with a 205% increase in mortality, but an LFI of 5.0 after LT increased it by only 42%. These findings suggest that patients with a high LFI may derive particular benefit from LT. Frailty should therefore be given greater consideration as a factor in the evaluation of LT patients alongside the established hepatological scoring systems.
The study aligns with the increasing awareness in hepatology that frailty in cirrhosis patients is a prognostic factor that should not be underestimated. In this context, however, it also seems important to point out that the assessment of frailty is still very heterogeneous. There is currently no consensus on the definition of frailty in cirrhotic patients. While the LFI, which consists of tests for grip strength, chair stands, and balance, is certainly one of the most relevant scores, a number of other tests are available, including the Clinical Frailty Scale (CFS), the Fried’s Frailty Score (FFS), the Short Physical Performance Battery (SPPB), and the Hospital Frailty Risk Score (HFRS).
This study is not without limitations:
a) As only outpatients on the waiting list for LT were included, the true prevalence of frailty is certainly underestimated.
b) It is only an observational study.
c) The transferability of the US cohort to Europe is questionable given the significant differences in the transplant systems.
Nevertheless, the findings provide a crucial impetus to incorporate frailty assessment more rigorously into the evaluation of LT candidates.