Identifying an Optimal Liver Frailty Index Cutoff to Predict Waitlist Mortality in Liver Transplant Candidates

Abstract

Background and aims: Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality.

Approach and results: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79.

Conclusions: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.

Figure 1.

Distribution of Liver Frailty Index scores for 1,405 outpatients with cirrhosis awaiting liver transplantation. Higher values indicate a higher degree of frailty.

Figure 2.

Locally weighted scatterplot smoothing curve showing the association between the Liver Frailty Index and waitlist mortality

Figure 3.

Comparison of the Liver Frailty Index + MELDNa versus MELDNa alone in 3-month waitlist mortality prediction

Figure 4.

Cumulative incidence of waitlist mortality for four patients with cirrhosis on the liver transplant waitlist classified by a combination of MELDNa and Liver Frailty Index scores. Liver Frailty Index scores (3.4 and 4.7) and MELDNa scores (14 and 23) were selected because they represented the bottom 20%ile and top 80%ile values for the cohort.