Dysregulated of monocyte function prior to liver transplant is associated with increased risk of post-transplant mortality 3930

Abstract Description Cirrhosis induces progressively severe immune dysfunction, which persists early after liver transplant (LT) and increases risk of morbidity and mortality both prior to and following LT. We have previously identified the Liver Immune Frailty Index (LIFI), a pre-LT biomarker panel (MMP-3 and Fractalkine), which stratifies patients into tertiles of risk for post-LT mortality. 1-yr post-LT mortality is 63% vs. 1.8% in LIFI-high and -low (c-statistic 0.83). Plasma and PBMCs were obtained at the time of liver transplant (T0) and stratified by LIFI (-low vs high/moderate). Bulk RNAseq demonstrates distinct gene expression profiles in LIFI-high/moderate vs LIFI-low. Notably, pathways related to toll-like receptors (TLRs) signaling and phagocytic activity were enriched, indicating innate immune involvement in pre-LT immune dysfunction. Single-cell RNAseq analysis of monocyte clusters identified CD14+ monocytes as major contributors to TLRs and pattern recognition receptors (PRRs) upregulation in T0 PBMCs. These changes could result from bacterial translocation due to cirrhosis-related increases in intestinal permeability and peripheral vasodilation prior to LT. Such increases in antigen presentation could trigger an excessive pro-inflammatory response by monocytes. Persistence of such monocyte dysregulation early after LT could contributing to ongoing immune dysfunction and increased susceptibility to infection, thus impacting risk of post-LT mortality. Funding Sources 1R01DK137222-01A1, 1R21AI180739-01A1 Topic Categories Transplantation Immunology (TRAN)