Transplant Trial Watch

Evolution of dynamic, biochemical, and morphological parameters in hypothermic machine perfusion of human livers: A proof-of-concept study.

Abudhaise H, Davidson BR, et al.

PLoS ONE, 2018; 13(9): e0203803.


Aims
The aim of this study is to evaluate the progression of dynamic, biochemical and histological markers during hypothermic machine perfusion (HMP) in the human liver, comparing arterial, oxygen-supplemented venous and non-oxygen-supplemented venous perfusion, and to study these markers in relation to organ quality.

Interventions
Livers were randomised at 2 stages: stage 1, 25 livers were randomised into static cold storage (SCS, n = 7), arterial perfusion through the hepatic artery (AP, n = 10), and non-oxygen-supplemented venous perfusion through the portal vein (nOVP, n = 8). In stage 2, 20 livers were randomised into oxygen-supplemented perfusion (OVP, n = 11) and non-oxygen-supplemented venous perfusion (nOVP, n = 9).

Participants
Forty five sequential livers (whole livers from deceased donors) procured for transplantation using the standard clinical procurement protocols adopted by the UK National Organ Retrieval Service (NORS) but found to be unsuitable for transplantation by UK transplant centres.

Outcomes
Outcomes assessed were continuous measurement of dynamic perfusion parameters (flow and vascular resistance), hepatocellular injury enzymes (alanine transaminase and aspartate transaminase) in the perfusate, and a score of morphological changes (based on enlargement of the space of Disse, sinusoidal dilatation, coagulation necrosis, congestion, architectural damage, and neutrophil infiltration).

Follow-up
Baseline to 4-hour preservation.

CET Conclusions
This was an experimental study using discarded human livers; the study was not blinded. Hepatic artery perfusion was associated with significantly higher resistance and lower flow than portal vein perfusion. Both groups showed a significant rise in liver enzymes during perfusion, with or without oxygenation. Morphological scoring was no different comparing static cold storage and HMP (via hepatic artery or portal vein, and with or without oxygen). Previous studies have shown that hepatic artery perfusion alone is associated with graft injury. It should be noted that no power calculation was performed for this study and despite being one of the largest studies in discarded human livers it is probably too small to establish differences in perfusion parameters and enzyme levels that would be clinically relevant. As there was no warm perfusion phase after cold preservation, there is no information here about how the effect of these methods might come to light during a reperfusion model or after reperfusion in a recipient.

Jadad score
3

Data analysis
Per protocol analysis

Allocation concealment
Yes

Trial registration
None

Funding source
Industry & non-industry funded