Preliminary Single-Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial

Abstract

After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single-center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded. Transplanted NMP grafts were matched 1:3 with transplanted SCS livers. Median NMP was 11.5 h (range 3.3-22.5 h) with one DCD liver perfused for 22.5 h. All transplanted livers functioned, and serum transaminases, bilirubin, international normalized ratio, and lactate levels corrected in NMP recipients similarly to controls. Graft survival at 30 days (primary outcome) was not statistically different between groups on an intent-to-treat basis (p = 0.25). Intensive care and hospital stays were significantly more prolonged in the NMP group. This preliminary experience demonstrates feasibility as well as potential technical risks of NMP in a North American setting and highlights a need for larger, randomized studies.

The bridge between transplantation and regenerative medicine: Beginning a new Banff classification of tissue engineering pathology

“…Regenerative medicine/tissue engineering can rehabilitate suboptimal donor organs, thereby considerably expanding the current donor organ pool, and has the potential to save the remaining 90%, by generating or repairing organs. Rapid advances are also being made in other areas to increase the donor pool, including xenotransplantation,2 tolerance induction,3 ex vivo perfusion,4 organ preservation and banking,5 and more traditional approaches 6. If the field of transplantation is to be increased tenfold or more in size to fill the expanding need for organ replacement, regenerative medicine will be the major cause of this improvement, but there will be many other secondary causes in addition.…”

Normothermic Machine Perfusion: A New World Deserving Careful Exploration

“…We read with interest "Preliminary Single-Center Canadian Experience of Human Normothermic Ex Vivo Liver Perfusion: Results of a Clinical Trial," by Bral et al (1). The authors compared their experience transplanting 10 livers using normothermic machine perfusion (NMP) with 30 historic controls matched on five different characteristics.…”

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

“…Although such a circuit might be considered more sterile due to lack of contact between the perfusate and ambient air, cannulating the inferior vena cava runs the risk of provoking hepatic congestion due to outflow resistance. As well, when the perfusion circuit is closed and all the effluent is recovered, it is very difficult to perform rapid cold perfusion to avoid graft loss in the case of technical malfunction during NMP/ subnormothermic machine perfusion (SMP) (44,49).…”

“…Indications to ex situ NMP, results and donor and recipient characteristics are quite heterogeneous. The first experiences, were performed as attempts to resuscitate very marginal grafts already discarded by most liver transplant centers (72,78) and so far, only three randomized prospective series have been reported (48,49,71). The first human liver transplant using ex situ NMP was published by the group in Birmingham in 2016 (78).…”