Normothermic Ex-vivo Liver Perfusion and the Clinical Implications for Liver Transplantation

Abstract

Despite significant improvements in outcomes after liver transplantation, many patients continue to die on the waiting list, while awaiting an available organ for transplantation. Organ shortage is not only due to an inadequate number of available organs, but also the inability to adequately assess and evaluate these organs prior to transplantation. Over the last few decades, ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation. Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage. However, these studies have not, necessarily, been translatable to human livers. Small animal studies have been essential in understanding and improving this technology. Similarly, these results have yet to be translated into clinical use. A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology. However, more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preservation. Here, we aimed to review all relevant large and small animal research, as well as human liver studies on normothermic ex-vivo perfusion, and to identify areas of deficiency and opportunities for future research endeavors.

Organ Restoration With Normothermic Machine Perfusion and Immune Reaction

“…Early NMLP studies (39,40) describe how perfusing the graft at a physiological temperature has been revived and is at the forefront of "bench to bedside" practice in transplantation.…”

Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion

“…Ex vivo normothermic perfusion has been extensively studied during the past decade and it has allowed to monitor function and circulation in marginal organs, such as in case of donation after circulatory death or from extended criteria donors, in kidney, lung, heart and liver transplantation studies and also to deliver certain therapeutic strategies (33)(34)(35). During ex vivo normothermic perfusion the donated organ undergoes machine perfusion with warm and oxygenated blood or preservation solution prior to transplantation.…”

A Narrative Review of the Applications of Ex-vivo Human Liver Perfusion

“…There are a number of commercially available machine perfusion devices in clinical use currently, including the "Liver Assist TM " (Organ Assist, Groningen, The Netherlands) and the portable "OrganOx metra TM " (OrganOx Ltd, Oxford, UK). The "Liver Assist TM " facilitates NMP and HMP whereas the "OrganOx metra TM " only permits NMP [7]. "VitaSmart TM " by Bridge to Life Ltd. (Northbrook, United States of America) is another multi-organ machine perfusion system currently being investigated in the USA in a randomised clinical trial of ischaemia reperfusion treatment using portal venous hypothermic oxygenated perfusion [8,9].…”