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

Abstract

Background: Experimental 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.

Methods: In 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.

Results: Ten 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).

Conclusion: This 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.

Figure 1

a–c Macroscopic view of a donor liver during machine perfusion. Liver graft with cannulas in the portal vein and supratruncal aorta during back‐table preparation, and before and after dual hypothermic oxygenated machine perfusion (DHOPE). The asterisk indicates a wet sterile gauze protecting the arteries. SCS, static cold storage

Figure 2

Schematic drawing of the set‐up of dual hypothermic oxygenated machine perfusion. The liver graft was placed in the reservoir, which was covered with a transparent lid to maintain a moist and sterile environment. The system was both pressure and temperature controlled. Two rotary pumps separately provided a pulsatile flow to the hepatic artery (HA) at a mean of 25 mmHg (pressure variation between 20 and 30 mmHg) and a continuous flow to the portal vein (PV) at 5 mmHg. The perfusion fluid was oxygenated by the membrane oxygenators, which also regulated the temperature (set to 10°C). Real‐time perfusion flow rates and temperature were measured by sensors and displayed on both pump units

Figure 3

Kaplan–Meier curves of a graft and b patient survival rates within the first year after transplantation in dual hypothermic oxygenated machine perfusion (DHOPE) and control groups. a P = 0·052, b P = 0·209 (log rank test)

Figure 4

Characteristics of dual hypothermic oxygenated machine perfusion. a Arterial and portal flow rates were measured by flow sensors attached to the tubing of the perfusion device. b Perfusion pressure (mmHg) was measured by pressure sensors attached to the arterial and venous tubing. Vascular resistance was calculated using Ohm's law and expressed as mmHg per ml per min per kg liver. c,d Levels of alanine aminotransferase (ALT), glucose and lactate were measured in perfusion fluid samples taken every 30 min during perfusion. Values are median (i.q.r.)

Figure 5

Post‐transplant biochemical markers of hepatic injury and function in dual hypothermic oxygenated machine perfusion (DHOPE) and control groups: a prothrombin time, b lactate, c alanine aminotransferase (ALT), d total bilirubin, e γ‐glutamyl transferase (GGT), f alkaline phosphatase (ALP). Day 0 was determined as the time interval between reperfusion and midnight. Values are median (i.q.r.). *P < 0·050 (Mann–Whitney U test)