Resuscitation and viability testing of initially declined livers using sequential hypo- and normothermic machine perfusion with an acellular fluid: First results of the DHOPE-COR-NMP Trial

Y.D.V. de Vries, A.P.M. Matton, S.A. Karangwa, O.B. van Leeuwen, M.W.N. Nijsten, R.H.J. de Kleine, A.P. van den Berg, H. Blokzijl, F. van der Heide, V.E.D.M. de Meijer, T.C.M.A. Schreuder, P. Meyer, M. Fujiyoshi, M.T. de Boer, R.J. Porte

Thursday 15 march 2018

11:30 - 11:40h at Van Rijck/Ruys Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 5: Clinical

Introduction

End-ischemic dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers serve different goals. While a short period of end-ischemic HOPE resuscitates mitochondria and reduces ischemia-reperfusion injury, NMP allows for ex-situ functional testing of donor livers. We established a combined protocol of one hour DHOPE, followed by controlled oxygenated rewarming (COR), and NMP for resuscitation and viability assessment of high risk donor livers that were initially declined for transplantation by all Dutch liver transplant centers (DHOPE-COR-NMP trial).

Methods

The DHOPE-COR-NMP trial (NTR5972) was initiated in July 2017 and three livers were included until October 2017. To facilitate machine perfusion at different temperatures an acellular perfusion fluid containing an hemoglobin-based oxygen carrier (HBOC) was developed. Livers were deemed transplantable if bile production was ≥ 10 g, biliary pH >7.45, and perfusate pH and lactate levels normalized within the first 150 minutes of the NMP phase.

Results

All three livers produced sufficient amounts of bile (median cumulative bile production 57 g at 150 minutes of NMP). Liver 1 reached normal perfusate pH and lactate levels, as well as a biliary pH of 7.55 within 150 min of NMP. Peak ALT in perfusate was 540 IU/L. This liver was successfully transplanted, with the recipient in excellent condition at 3 months of follow-up. Liver 2 reached normal perfusate pH and lactate levels within 150 min of NMP, but biliary pH was 7.39. Peak ALT in perfusate was 4215 IU/L. Liver 3 did not reach normal perfusate pH and lactate levels during viability assessment. Moreover, biliary pH was 7.32. Peak ALT in perfusate was 8460 IU/L. Both livers 2 and 3 did not meet the viability criteria and were therefore discarded.

Conclusion

Sequential DHOPE, COR and NMP, using an acellular fluid containing an HBOC, is feasible and enables both resuscitation and viability testing of high risk donor livers prior to transplantation. This protocol provides a tool to expand the donor pool by selecting donor livers that can be transplanted safely despite initial decline based on a high-risk donor profile.