Criteria for viability assessment of discarded human donor livers during ex-vivo normothermic machine perfusion

Abstract

Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37uC with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion.

Current challenges and future directions for liver transplantation

“…The efficacy of NPM in preserving the biliary tree from the ischaemic damage was demonstrated in 12 discarded human livers and the bile production during NPM was used as a predictor graft function, enabling viability testing. 71,72 Data obtained in the animal models and in discarded human livers provide convincing evidence that MP is very effective in protecting biliary three from ischaemic damage. It could be anticipated that the extensive use of MP can lead to a significant increase in the availability of transplant livers as well as a significant reduction in several types of graft dysfunction and biliary complications.…”

Normothermic machine perfusion of the liver

“…Our current understanding of the liver viability testing is based on several experimental studies. Using discarded human donor livers, Sutton et al 4 reported hourly bile production volume to be a marker of liver function, whereas Watson et al 5 suggested sequential perfusate liver transaminases levels may predict the liver function. The most widely accepted method of viability tested was described by the Birmingham group in a pilot study in humans of five liver transplants performed using livers initially declined for transplantation that were subjected to NMP-L viability testing.…”

Suitability of livers for transplantation when treated by normothermic machine perfusion

“…The "ex vivo" evaluation of liver function with NMP has been the focus of numerous studies 14,20,21 ; however, the definition of a viable graft is still a matter for debate and research. Continuous bile production and the normalization of lactate levels, which reflect the restoration of normal metabolic activity, 21 seem to be the two most reliable indicators of organ viability.…”

“…12 To evaluate organ viability, it is essential to restore full metabolism through normothermic perfusion. 13,14 This involves perfusing blood products through the arterial and portal routes at subphysiologic pressure. The first series of patients undergoing engraftment with organs treated by preimplantation NMP was reported recently, and this confirmed its feasibility in clinical practice.…”