The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation

Abstract

Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult because of the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable, and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical LT and in an experimental DCD model. Graft preservation solutions of 83 liver grafts at the end of cold ischemia were analyzed for miRNAs by reverse transcription polymerase chain reaction. Of these grafts, 42% developed EAD after transplantation. Results were verified in pig livers (n = 36) exposed to different lengths of warm ischemia time (WIT). The absolute miR-122 levels and miR-122/miR-222 ratios in preservation fluids were significantly higher in DCD grafts (P = 0.001) and grafts developing EAD (P = 0.004). In concordance, the miR-122/miR-222 ratios in perfusion fluid correlate with serum transaminase levels within the first 24 hours after transplantation. Longterm graft survival was significantly diminished in grafts with high miR-122/miR-222 ratios (P = 0.02). In the porcine DCD model, increased WIT lead to higher absolute miR-122 levels and relative miR-122/miR-222 ratios in graft perfusion fluid (P = 0.01 and P = 0.02, respectively). High miR-122/miR-222 ratios in pig livers were also associated with high aspartate aminotransferase levels after warm oxygenated reperfusion. In conclusion, both absolute and relative miR-122 levels in graft preservation solution are associated with DCD, EAD, and early graft loss after LT. As shown in a porcine DCD model, miRNA release correlated with the length of WITs. Liver Transplantation 23 946–956 2017 AASLD.