Machine perfusion of the liver: Putting the puzzle pieces together

Table 1 Potential benefits of the different modalities of machine perfusion of the liver on clinical studies

	Safety and feasibility	Prevention of early allograft dysfunction	Prevention of biliary complications	Prolonged preservation time	Viability assessment	Therapeutic interventions
Normothermic regional perfusion1	Yes[11,19,46]	Yes[11,19,46]	Yes[11,19,46]	No data available yet	Yes[11,46]	No data available yet
Normothermic machine perfusion	Yes[2,6,21,42,50,51]	Yes[2,6,42]	No data available yet	Yes[2,6]	Yes[6,24,26,50,51]	Yes[43]2
Subnormothermic machine perfusion	No data available yet	No data available yet	No data available yet	No data available yet	No data available yet	No data available yet
Hypothermic machine perfusion	Yes[3,37]	Yes[3,37]	Yes[3,22,37]	Yes[39]2	Yes[34]	No data available yet
Controlled oxygenated rewarming	Yes[9,47]	Yes[9,47]	No data available yet	No data available yet	No data available yet	No data available yet
Combined modalities (HMP + NMP)	Yes[14,15]	No data available yet	No data available yet	Yes[39]2	Yes[14,15]	No data available yet
Ischaemia-free liver transplantation3	Yes[12,48]	Yes[48,49]	No data available yet	No data available yet	No data available yet	No data available yet

¹Only suitable for donors after circulatory death.

²Only pre-clinical studies available so far.

³Only suitable for donors after brain death. HMP: Hypothermic machine perfusion; NMP: Normothermic machine perfusion.

Table 2 Parameters employed in clinical studies to assess the viability of donor organs before transplantation

Ref.	Method	Perfusate parameters	Bile parameters	Perfusion parameters
Watson et al[11]	NRP	Within 2 h of NRP: Alanine transaminase up to 500 IU/L, providing no continued rise between the first and second hours
Muller et al[34]	HMP	At least 1 h of HMP: Threshold at 10000 A.U. (100 ng FMN/mL perfusate) to refuse livers regardless of the use of a DCD or DBD liver
Watson et al[32]	NMP	No timepoint defined: Changes in lactate, glucose, and transaminase concentrations and the ability of the liver to maintain perfusate pH without supplemental bicarbonate
Matton et al[26]	NMP		Within 2.5 h of NMP: Bicarbonate concentration > 18 mmol/L, pH > 7.48, glucose concentration < 16 mmol/L, bile/perfusate glucose concentration ratio < 0.67, and LDH concentration < 3689 U/L
de Vries et al[14]	NMP	Within 150 min of NMP: Lactate concentration within “normal” values (0.5-1.7 mmol/L); pH within normal values (7.35-7.45), without continuing sodium bicarbonate supplementation	Within 150 min of NMP: Cumulative bile production of ≥ 10 mL and ≥ 4 mL in the preceding hour. pH > 7.45
Mergental et al[6]	NMP	Within 4 h of NMP: Lactate ≤ 2.5 mmol/L; and two or more parameters: pH ≥ 7.30; Evidence of glucose metabolism	Within 4 h of NMP: Evidence of bile production	Within 4 h of NMP: HA flow ≥ 150 mL/min and PV flow ≥ 500 mL/min; and homogenous perfusion of the parenchyma
Cardini et al[50]	NMP	Within 2 h of NMP: Rapid decrease and maintenance of lactate to physiological levels, maintenance of physiological pH values without sodium bicarbonate supplementation, and glucose consumption. Remarkably high transaminases and LDH levels and a severe rise of these parameters are deemed warning signals	Within 2 h of NMP: Bile production and bile pH are indicators for bile duct viability and function
Reiling et al[51]	NMP	Within 2 h of NMP: Lactate clearance to < 2 mmol/L. Within 4 h of NMP: Evidence of glucose metabolism. Maintenance of physiological pH without continuing administration of sodium bicarbonate	Within 4 h of NMP: Bile production (no lower limit)	Within 4 h of NMP: Stable hepatic arterial and portal venous flows. Homogeneous graft perfusion with soft consistency of parenchyma

DCD: Donation after circulatory death; DBD: Donation after brain death; HA: Hepatic artery; HMP: Hypothermic machine perfusion; LDH: Lactate dehydrogenase; NMP: Normothermic machine perfusion; NRP: Normothermic regional perfusion; PV: Portal vein.