Increased and safe utilization of high-risk donor livers for transplantation after ex situ resuscitation and assessment using sequential hypo- and normothermic machine perfusion

Abstract

Background: Despite persistent donor organ shortage, a high number of donor livers is currently not used for transplantation. We aimed to increase the number of transplantable livers by resuscitating and assessing hepatobiliary viability of initially declined high-risk livers using a protocol of end-ischemic sequential ex situ hypothermic and normothermic machine perfusion. Method: In this prospective clinical trial, all nationwide declined livers were eligible for inclusion (Netherlands Trial Registry NTR5972). The protocol consisted of one hour hypothermic oxygenated perfusion (10°C) for resuscitation, one hour of controlled oxygenated rewarming, and subsequent normothermic machine perfusion (NMP) for viability testing. A perfusion fluid containing a hemoglobin-based oxygen carrier was used for all temperature phases. During the first 150 min of NMP, viability of liver and biliary tree was assessed, using the following criteria: perfusate lactate <1.7mmol/L, pH 7.35-7.45, cumulative bile production >10mL and biliary pH>7.45. Livers meeting these criteria were secondary accepted for transplantation. All recipients gave written informed consent. Primary endpoint was safety and feasibility, as reflected by a 3-months graft survival rate of at least 80%. Results: Between August 2017 and October 2018, 16 livers underwent machine perfusion after an average of 288 (241-480) min of static cold preservation. All livers were derived from donation after circulatory death donors, with a median age of 63 (range 42-82) years. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 cases biliary pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, increasing the number of deceased donor liver transplants by 20%. Patient and with graft survival at 3 months was 100%. Conclusion: Sequential hypo- and normothermic machine perfusion enabled resuscitation and selection of initially declined high-risk donor livers. This method offered a valuable tool to safely increase the number of transplantable livers by 20%.