• Andrea Schlegel, Philipp Kron, Rolf Graf, Pierre-Alain Clavien, and Philipp Dutkowski.
• *Laboratory of the Swiss HPB and Transplant Center, Department of Surgery, University Hospital Zurich, Switzerland †Hospital Paul Brousse, Université Paris Sud, Paris, France.
• Ann. Surg.. 2014 Nov 1;260(5):931-7; discussion 937-8.

ObjectiveTo evaluate the impact of a novel oxygenated perfusion approach on rejection after orthotopic liver transplantation (OLT).BackgroundHypothermic oxygenated perfusion (HOPE) was designed to prevent graft failure after OLT. One of the mechanisms is downregulation of Kupffer cells (in situ macrophages). We, therefore, designed experiments to test the effects of HOPE on the immune response in an allogeneic rodent model of nonarterialized OLT.MethodsLivers from Lewis rats were transplanted into Brown Norway rats to induce liver rejection in untreated recipients within 4 weeks. Next, Brown Norway recipients were treated with tacrolimus (1 mg/kg), whereas in a third group, liver grafts from Lewis rats underwent HOPE or deoxygenated machine perfusion for 1 hour before implantation, but recipients received no immunosuppression. In a last step, low-dose tacrolimus treatment (0.3 mg/kg) was assessed with and without HOPE.ResultsAllogeneic OLT without immunosuppression led to death within 3 weeks after nonarterialized OLT due to severe acute rejection. Full-dose tacrolimus prevented rejection, whereas low-dose tacrolimus led to graft fibrosis within 4 weeks. HOPE treatment without immunosuppression also protected from lethal rejection. The combination of low-dose tacrolimus and 1-hour HOPE resulted in 100% survival within 4 weeks without any signs of rejection.ConclusionsWe demonstrate that allograft treatment by HOPE not only protects against preservation injury but also impressively downregulates the immune system, blunting the alloimmune response. Therefore, HOPE may offer many beneficial effects, not only to rescue marginal grafts but also by preventing rejection and the need for immunosuppression.

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