Identification and Internal Validation of a Novel Pre-Transplant Biomarker Panel to Predict Mortality Following Liver Transplantation: The Liver Immune Frailty Index

Abstract

Abstract Cirrhosis-related immune dysfunction is well recognized and may contribute to early mortality following liver transplant (LT). The purpose of the present study was to identify pre-transplant biomarkers of immune dysfunction (i.e., immune frailty) that might accurately predict risk of early mortality following LT. Patient plasma was collected immediately prior to LT (T0) and analyzed via Luminex (N=279). On multivariate analysis, HCV IgG, Fractalkine, and MMP3 were significant predictors of 1yr post-LT mortality and were utilized to comprise a novel Liver Immune Frailty Index (LIFI). The LIFI stratifies LT recipients into -low, -moderate, and –high risk tertiles. One-year mortality was 1.4% for LIFI-low, 12.7% for LIFI-moderate, and 58.3% for LIFI-high. Internal validation through bootstrap resampling with 2000 replicates demonstrated the final LIFI model predicts early post-LT mortality with C-statistic=0.84. This novel index may identify patients at risk for persistent severe immune dysfunction and early mortality following LT.