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

O.B. van Leeuwen, Y. de Vries, M. Fujiyoshi, R. Ubbink, G.J. Pelgrim, M.J.M. Werner, K. Reyntjens, A.P. van den Berg, M.T. de Boer, R.H.J. de Kleine, V.E. de Meijer, R.J. Porte

Wednesday 13 march 2019

14:28 - 14:30h at Mauritszaal

Categories: Klinisch, Parallelsessie

Parallel session: Parallelsessie IV - Klinisch I

Background: Despite persistent donor organ shortage, a high number of donor livers is currently not used for transplantation because of a supposed too high risk of early graft dysfunction/loss. 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 situhypothermic and normothermic machine perfusion.

Methods: 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 novel perfusion fluid containing a hemoglobin-based oxygen carrier was used for all temperature phases. During the first 150 min of NMP viability of the 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 below 7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, resulting in a 20% increase in the number of deceased donor liver transplants. Patient and graft survival at 3 months was 100%. Comparison of non-transplanted and transplanted livers revealed median donor hepatectomy time (70 [IQR 44-93] min vs. 44 [IQR 28-54] min; p=0.04) and median cold ischemia time (326 [IQR 286-480] min vs. 270 [IQR 241-294] min; p=0.02) as variables significantly associated with secondary graft acceptance during NMP.

Conclusions: 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%.