Effect of Aprotinin on Liver Injury after Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis

The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. In this single center retrospective analysis of 84 propensity score matched patients out of 274 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR 1,6, AST/ALT > 2000 within 7–10 days) and recipient survival. The incidence of PRS (52.4% vs. 47.6%) and 30-day mortality did not differ (4.8 vs. 0%; p = 0.152) but patients treated with aprotinin suffered more often from EAD (64.3% vs. 40.5%, p = 0.029) compared to controls. Acceptable or poor (OR = 3.3, p = 0.035; OR = 9.5, p = 0.003) organ quality were independent predictors of EAD. Our data do not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

The Utility of Extended Criteria Donor Livers in High Acuity Liver Transplant Recipients

Background Although the use of extended criteria donor (ECD) liver allografts has gained momentum as a potential method by which to expand the donor pool, their use largely remains relegated to low acuity liver transplant (LT) recipients. Thus, we sought to examine whether such grafts also have utility in high acuity (Model for End-Stage Liver Disease [MELD] ≥ 35) recipients. Study Design Extended criteria donors were defined as donor age > 60 years, hepatitis C virus positive donor, split livers, livers with cold ischemia time > 12 h, donor after cardiac death livers, or having macrosteatosis > 30%. Outcomes were compared between standard liver (SL) and ECD grafts in recipients with MELD ≥ 35. Results Of 225 patients, 46 (20.4%) received an ECD liver and 179 (79.6%) received a SL. Extended criteria donor graft recipients had significantly higher levels of post-LT maximal transaminases and rate of early allograft dysfunction. Nonetheless, high acuity ECD graft recipients had similar short- and long-term patient survival compared to SL recipients, with 1-,3-, and 5-year survivals of 86.9%, 82.3%, 79.3% and 86.9%, 80.5%, and 75.4%, respectively ( P = .674). There were also no significant differences in graft survival or rejection-free survival between the 2 groups. Conclusion The lack of inferior patient/graft survival among high acuity ECD graft recipients suggests that ECD livers present a viable method by which to expand the donor pool for this group of patients.

Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique.Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling.Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases.Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

Effect of Aprotinin on Liver Injury After Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis

Background: The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. Methods: In this single center retrospective analysis of 84 propensity score matched patients out of 290 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR  1,6, AST/ALT >2000 within 7-10 days) and recipient survival. Results: The Incidence of PRS (52,4% vs 47,6%) and 30-day mortality did not differ (4.8 vs 0%; p=0.152) but patients treated with aprotinin suffered more often from EAD (64,3% vs 40,5%, p=0.029) compared to controls. Acceptable or poor (OR=3.3, p=0.035; OR=9.5, p=0.003) organ quality were independent predictors of EAD. Conclusion: Our data does not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs

Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.