Development and Internal Validation of a Novel Pre-Transplant Biomarker Panel to Predict Post-Liver Transplant Mortality

Abstract

Current scoring systems accurately predict risk of pre-liver transplant (LT) mortality but fall short in estimation of post-LT survival. This study seeks to identify biomarkers of pre-LT immune dysfunction that predict mortality following LT. From 10/1/13-3/23/21, 279 cirrhotic patients underwent assessment of plasma biomarker (Luminex) and clinical variables immediately prior to LT (T0). Cox-proportional hazards modeling identified HCV IgG, Fractalkine, and MMP3 as multivariate predictors of 1-year mortality, with covariate selection by clinical importance and LASSO methodology. These were utilized to comprise the novel Liver Immune Frailty Index (LIFI), which stratifies recipients into -low, -moderate, and –high risk tertiles. One-year mortality was 1.4%, 12.7%, and 58.3% for LIFI-low, -moderate, and -high, respectively. Internal validation through bootstrap resampling with 2000 replicates demonstrates LIFI predicts early post-LT mortality with C-statistic=0.84 and Brier score of 0.04. LIFI may identify patients at risk for persistent severe immune dysfunction and early mortality following LT.