Metabonomic Profile of Macrosteatotic Allografts for Orthotopic Liver Transplantation in Patients With Initial Poor Function: Mechanistic Investigation and Prognostic Prediction

摘要

Background: Our previous study revealled amplified hazardous effects of macrosteatosis (MaS) on graft failure (GF) in recipients with severe liver damage in short post-operative days, with vague mechanism inside. Aim: We aimed to uncover the molecular mechanism of donor MaS on GF, and construct the predictive model to monitor post-transplant prognosis based on “omics” perspective. Methods: Ultra-performance liquid chromatography coupled to mass spectrometry metabolomic analysis was performed in allograft tissues from 82 patients with initial poor function (IPF) from multi-liver transplant (LT) centers. Pathway analysis was performed by on-line toolkit Metaboanalyst (v 3.0). Predictive model was constructed based on combinative metabonomic and clinical data extracted by stepwised cox proportional analysis. Results: Principle component analysis (PCA) analysis revealled stratification on metabolic feature in organs classified by MaS status. Differential metabolits both associated with MaS and GF were significantly enriched on pathway of glycerophospholipid metabolism (P0.05). Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) involved in glycerophospholipid metabolism was significantly decreased in cases with MaS donors and GF (P0.05). Better prediction was observed on graft survival by combinative model (area under the curve=0.91) and confirmed by internal validation. Conclusion: Metabonomic features of allografts can be clearly distinguished by MaS status in patients with IPF. Dysfunction on glycerophospholipid metabolism was culprit to link donor MaS and final GF. Decrement on PC and PE exerted the fatal effects of MaS on organ failure. Metabonomic data might help for monitoring long-term graft survival after LT.