Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures of early mortality in acute liver failure

Acute liver failure (ALF) has high mortality predominantly due to compromised immune system and increase vulnerability to bacterial and fungal infections. Plasma lipidome and fungal peptide-based-community (mycobiome) analysis were performed in Discovery cohort (40-ALF, 5-healthy) and validated in a validation cohort of 230-ALF using High-resolution-mass-spectrometry, artificial-neural-network (ANN) and machine-learning (ML). Untargeted lipidomics identified 2,013 lipids across 8 lipid-groups. 5 lipid-species (Phosphatidylcholine, PC(15:0/17:0), PC(20:1/14:1), PC(26:4/10:0), PC(32:0) and TG(4:0/10:0/23:6)) significantly differentiated ALF-NS (FC>10, p1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-non-survivors. In ALF plasma lipidome and mycobiome are dysregulated. Increase circulating phosphatidylcholine could stratify ALF predisposed to early-mortality or require emergency liver transplantation.