Abbreviations: ALT, alanine transaminase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BMI, body mass index; COG, clusters of orthologous groups of proteins; DCD, donation after cardiac death; EAD, early allograft dysfunction; ECD, extended criteria donors; GO, gene ontology; HOPE, hypothermic oxygenated machine perfusion; iTRAQ, isobaric Tags for Relative and Absolute Quantification; IRI, ischemia reperfusion injury; KEGG, kyoto encyclopedia of genes and genomes; L-FABP, liver fatty acid binding protein; LDH, lactate degyfrogenase; LT, liver transplantation; MRM, multiple reaction monitoring; NMP, normothermic machine perfusion; OG, optimal graft; PNF, primary nonfunction; SDS-PAGE, sodium dodecyl sulfate -polyacrylamide gel electrophoresis; TBIL, total bilirubin; L-FABP -a biomarker of liver donor quality in liver transplantation Abstract: Background: To a large extent the success of liver transplantation depends on quality of allografts. The molecular basis of the susceptibility of different liver allografts to transplant injury remains undefined. Methods: Transplanted liver samples were collected and divided into three groups: the optimal graft (OG) group, early allograft dysfunction (EAD) group, and primary nonfunction (PNF) group. iTRAQ comparative quantitative proteomic analysis and multiple reaction monitoring (MRM) verification was performed.Results: More than 160 differentially expressed proteins were detected in the PNF group, compared to 54 and 36 proteins in the EAD and OG groups respectively.Liver-type fatty acid-binding protein (L-FABP) was found as differentially expressed in both cold preserved and reperfused liver. Serum L-FABP level in donors was higher in the PNF and EAD groups than in the OG group. A lower tissue expression of L-FABP was observed in the PNF groups than other groups after reperfusion, indicating incompetent liver donor quality. In mouse ischemia reperfusion injury (IRI) model, the serum levels and tissue expression of L-FABP corresponded to the ALT variation curve.
Conclusions:Suboptimal donor livers are more sensitive to ischemia reperfusion injury. L-FABP might be an effective biomarker for evaluating donor quality in liver transplantation.