Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death

Abstract

BackgroundExperimental studies have suggested that end‐ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case–control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation.MethodsIn consecutive DCD liver transplantations, liver grafts were treated with end‐ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End‐stage Liver Disease (MELD) score. All patients were followed for 1 year.ResultsTen transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6‐month and 1‐year graft and patient survival rates were 100 per cent in the DHOPE group. Six‐month graft survival and 1‐year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5′‐triphosphate (ATP) content increased 11‐fold, from 6 (3–10) to 66 (42–87) µmol per g protein (P = 0·005). All DHOPE‐preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7–1·4) versus 2·6 (0·9–5·1) mg/dl, P = 0·044). None of the ten DHOPE‐preserved livers required retransplantation for non‐anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140).ConclusionThis clinical study of end‐ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post‐transplant biliary complications.

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

“…2,3,6 The latter might explain why postoperative peak ALT was lower in our recipients than in the studies that compared SCS to end-ischemic NMP alone. has been shown to reduce ischemia reperfusion injury via resuscitation of the mitochondria and the increase in hepatic ATP content, thereby also protecting the hepatocytes.…”

“…2 During NMP an air/oxygen mixture was used aimed to reach an arterial perfusate pO 2 of 10.0-13.3 kPa and a venous oxygen saturation of 55% to 75%. 2 During NMP an air/oxygen mixture was used aimed to reach an arterial perfusate pO 2 of 10.0-13.3 kPa and a venous oxygen saturation of 55% to 75%.…”

“…[1][2][3][4][5] (Dual) hypothermic oxygenated perfusion ([D]HOPE) can be applied to resuscitate the mitochondria and increase hepatic adenosine triphosphate (ATP) content, resulting in less cell injury, including less choliangiocyte injury. Machine perfusion, was recently introduced in clinical practice using two different temperature protocols: hypothermic (4-12°C) or normothermic (37°C) machine perfusion.…”

Hypothermic oxygenated machine perfusion alleviates liver injury in donation after circulatory death through activating autophagy in mice

“…However, due to the shortage of donors, liver donation after circulatory death (DCD) has gradually begun to be utilized, and an increasing number of scholars apply hypothermic machine perfusion (HMP) or hypothermic oxygenated machine perfusion (HOPE) to relieve DCD liver injury. These methods may become indispensable ways to preserve livers …”

Organ Preservation into the 2020s: The Era of Dynamic Intervention

“…Van Rijn et al [121] tested dual hypothermic oxygenated machine perfusion over donation after cardiac death (DCD) livers. The biliary outcomes were also encouraging; none of the preserved livers required retransplantation for nonanastomotic biliary stricture, as opposed to 5 of 20 livers in the control group.…”