Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

TLDR

Sequential dual hypothermic oxygenated machine perfusion (DHOPE) followed by normothermic machine perfusion (NMP) can complement each other, with DHOPE restoring mitochondrial ATP and NMP enabling viability assessment, but conventional NMP relies on red blood cells, which have limitations at low temperatures. The study aimed to develop a protocol combining DHOPE, controlled oxygenated rewarming, and NMP using a hemoglobin‑based oxygen carrier perfusion fluid. Seven donation‑after‑circulatory‑death livers initially deemed unsuitable were subjected to the DHOPE‑COR‑NMP protocol, and were considered transplantable when perfusate pH and lactate normalized, bile production reached ≥10 mL, and biliary pH exceeded 7.45 within 150 minutes of NMP. Five of the seven livers were transplanted, achieving a 100 % graft survival at 3 months, demonstrating that the HBOC‑based sequential perfusion provides a novel method for resuscitating and testing suboptimal livers before transplantation.

Abstract

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was ≥10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation.