Long-term Outcomes After Controlled Oxygenated Rewarming of Human Livers Before Transplantation

Background. Controlled oxygenated rewarming (COR) has been shown to be a feasible and safe method in clinical practice and to reduce peak serum transaminases after liver transplantation. This study aimed to demonstrate further clinical experience of this method of now 18 clinical liver transplantations utilizing COR and demonstrate the long-term results. Methods. In this extended series of 18 patients, cold-stored livers were subjected to machine-assisted slow COR for ≈120 minutes before transplantation. A cohort of 178 patients transplanted during the same period with similar clinical characteristics were used for comparison of key outcomes. Results. All livers were perfused in accordance to the COR protocol without incidences and transplanted successfully. Early allograft dysfunction was observed in 2 (11.1%) cases after COR. Liver elasticity measurements indicated normal healthy liver parenchyma at the last follow-up. Graft survival demonstrated excellent outcomes after COR. The 1-, 3-, and 5-year patient survival rates were 100%, 100%, and 93.8% compared with 84.5%, 82.0%, and 75.8% in the control group (P = 0.12). Conclusions. The present study demonstrates excellent clinical outcomes after COR before liver transplantation. Comparison with a control cohort shows superiority of graft survival. Further evidence is needed to assess this promising method to improve organ preservation, finally.

[1]  G. Martucci,et al.  Normothermic Machine Perfusion in Liver Transplantation: Feasibility and Promise of Avoiding Recooling Before Engrafting , 2019, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  J. van Praagh,et al.  Peribiliary Glands Are Key in Regeneration of the Human Biliary Epithelium After Severe Bile Duct Injury , 2019, Hepatology.

[3]  N. Heaton,et al.  A randomized trial of normothermic preservation in liver transplantation , 2018, Nature.

[4]  J. Pirenne,et al.  Adult Liver Allocation in Eurotransplant , 2017, Transplantation.

[5]  T. Minor,et al.  Prediction of Hepatocellular Preservation Injury Immediately Before Human Liver Transplantation by Controlled Oxygenated Rewarming , 2016, Transplantation Direct.

[6]  H. Reis,et al.  End‐ischemic reconditioning of liver allografts: Controlling the rewarming , 2016, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[7]  T. Minor,et al.  Controlled Oxygenated Rewarming of Cold Stored Livers Prior to Transplantation: First Clinical Application of a New Concept , 2016, Transplantation.

[8]  P. Clavien,et al.  First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis. , 2015, Annals of surgery.

[9]  T. Minor,et al.  Donor information based prediction of early allograft dysfunction and outcome in liver transplantation , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[10]  J. Emond,et al.  Hypothermic Machine Preservation Facilitates Successful Transplantation of “Orphan” Extended Criteria Donor Livers , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  J. Markmann,et al.  Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. , 2014, Journal of hepatology.

[12]  T. Minor,et al.  Controlled Oxygenated Rewarming of Cold Stored Liver Grafts by Thermally Graduated Machine Perfusion Prior to Reperfusion , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  G. Gerken,et al.  Optimized endoscopic treatment of ischemic-type biliary lesions after liver transplantation. , 2012, Gastrointestinal endoscopy.

[14]  Philipp Dutkowski,et al.  Are There Better Guidelines for Allocation in Liver Transplantation?: A Novel Score Targeting Justice and Utility in the Model for End-Stage Liver Disease Era , 2011, Annals of surgery.

[15]  F. Rauchfuß,et al.  DTG Procurement Guidelines in Heart Beating Donors , 2011, Transplant international : official journal of the European Society for Organ Transplantation.

[16]  H. Akkız,et al.  Infectious complications in the early postoperative period in liver transplant patients. , 2010, Minerva gastroenterologica e dietologica.

[17]  M. Abecassis,et al.  Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[18]  J. McAnulty.  Hypothermic organ preservation by static storage methods: Current status and a view to the future. , 2010, Cryobiology.

[19]  T. Minor,et al.  Energy charge restoration, mitochondrial protection and reversal of preservation induced liver injury by hypothermic oxygenation prior to reperfusion. , 2009, Cryobiology.

[20]  C. Sima,et al.  The Survival Benefit of Deceased Donor Liver Transplantation as a Function of Candidate Disease Severity and Donor Quality , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[21]  H. de Groot,et al.  Iron-dependent vs. iron-independent cold-induced injury to cultured rat hepatocytes: a comparative study in physiological media and organ preservation solutions. , 2007, Cryobiology.

[22]  P. Clavien,et al.  Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  J. Bragg-Gresham,et al.  Characteristics Associated with Liver Graft Failure: The Concept of a Donor Risk Index , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  R. Porte,et al.  Biliary complications after liver transplantation: A review , 2006, Scandinavian journal of gastroenterology. Supplement.

[25]  S. Dufour,et al.  Mitochondrial permeability transition during hypothermic to normothermic reperfusion in rat liver demonstrated by the protective effect of cyclosporin A. , 1998, The Biochemical journal.