Due to the organ shortage, inferior quality livers from donors after circulatory arrest (DCD) are offered to relieve mortality on the waiting list. The threshold to accept DCD livers is high and many livers are declined for safety reasons. Objective testing of these livers after retrieval could significantly increase the donor pool. The LiMAx (maximum liver function capacity) test is a functional test based on metabolism of ¹³C-methacetin, measured in exhaled air. A LiMAx value over 100 [micro]g/kg/h indicates good clinical outcome after liver resection and transplantation. We used this breath test in a novel way to assess the liver metabolism of grafts during ex vivo normothermic machine perfusion (NMP).

In a pig DCD model, grafts were retrieved after 15, 30 or 45 minutes of donor warm ischemia (DWIT) and perfused with UW preservation solution. After a cold ischemia time of 3 hours, livers were reperfused using NMP with the pig's own blood. After one hour of stabilization, LiMAx testing was performed.

In addition, two human DCD livers declined for transplantation were put on NMP with human blood for 150-210 min. After one hour, the LiMax test was performed and analysis was done similar to the pig experiments.

In the pigs, lactate level was 2.9 mmol/l at start NMP. AST increased from 50 to 412 IU/ml during NRP.

After 1 hour of NMP, lactate levels increased 2.0x, 2.5x and 5.6x in 15, 30 and 45 min of DWIT respectively. LiMAx values could be determined from the oxygenator filter of the NMP machine. In all pigs with 15 or 30 min of DWIT, a signal was recorded (891-3191 [micro]g/kg/h), whereas no signal was recorded after 45 min of DWIT.

The two human DCD livers showed LiMAx values of 650 and 2694 [micro]g/kg/h. Cold ischemic storage times were 64 and 5 hours in these livers, respectively. After reperfusion on NMP, the low LiMAx liver showed serious liver damage (AST 122269, ALT 97171, and gGT 205), whereas the high LiMAx liver showed liver values comparable to normal clinical values in DCD transplantation (AST 3317, ALT 3800, and gGT 3). Bilirubin was low in both (12 and 3 [micro]mol/L).

In conclusion, the LiMAx test is feasible in NMP and showed agreement with increased lactate production. However, the clinically accepted threshold cannot be used to discriminate between functional and defective livers on NMP, and substrate titration is needed.

CITATION INFORMATION: Schurink J., de Haan J., Verstegen M., Metselaar H., Ijzermans J., de Jonge J. The Use of LiMAx for Evaluating Donor Livers on Normothermic Machine Perfusion Am J Transplant. 2017;17 (suppl 3).

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