This will be a randomized study on the effects of hypothermic oxygenated machine perfusion in patients undergoing liver transplantations from donors after brain death with allocation of patients to either end-ischemic hypothermic oxygenated machine perfusion group (at least 2 hours of allograft perfusion at 12 degrees Celsius though hepatic artery and portal vein prior to implantation) or simple cold storage group in a 1:3 ratio. The primary outcome measure of the study will be model for early graft dysfunction (MEAF) score. A total number of 104 patients, including 26 in the hypothermic perfusion group and 78 in simple cold storage group will be included. Data on potential risk factors for worse allograft function and increased ischemia-reperfusion injury will be collected perioperatively. Circulating levels of proinflammatory cytokines (IL-2, IL-10, TNFα), nuclear damage (HMGB-1, 8-OHdG), serum activity of transaminases, gamma-glutamyl-transpeptidase, bilirubin concentration, and INR will be assessed in the perioperative period. Wedge allograft biopsies will be performed 90 minutes post-reperfusion to evaluate activation of innate immunity (TLR4), activation of endothelium (vWF, P-selectin), hepatocyte necrosis, hepatocyte apoptosis (TUNEL assay), ATP content, and oxidative damage (malondialdehyde content). Further, wedge biopsies will be performed at the end of simple cold storage and at the beginning and after two hours of perfusion to determine steatosis and ATP content. During the perfusion, perfusate samples will be periodically tested for lactate, sodium, and potassium concentration, CO2 partiall pressure, and flavin mononucleotide concentration. Patients will be closely monitored in the postoperative period for allograft function and secondary end-points: 2-year recipient and graft survival, 2-year incidence of biliary complications, and 90-day complication rate. Both groups will be compared with respect to the primary and secondary end-points, circulating levels of IL-2, IL-10, TNFα, HMGB-1, 8-OHdG, activity of transaminases and gamma-glutamyl-transpeptidase, and findings in post-reperfusion allograft biopsies. Further, changes of hepatic steatosis and hepatic ATP content during perfusion will be evaluated, and the results of perfusate analyses will be tested as predictors of allograft function in the post-transplant period.
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Model for early graft dysfunction score
Timeframe: 3 days