Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Abstract

Joint first authors. ISRCTN 14355416.The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ) versus , p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.Abbreviations: AST, aspartate transaminase; DBD, donation after brain death; DCD, donation after circulatory death; IRI, ischemia-reperfusion injury; IVC, inferior vena cava; MELD, model for end-stage liver disease; NHSBT, National Health Service Blood and Transplant; NMP, normothermic machine perfusion

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

“…In addition to cannulating liver inflow, there are liver MP devices requiring cannulation of the hepatic outflow (44,48). 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.…”

“…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).…”

Response to “Normothermic Machine Perfusion: A New World Deserving Careful Exploration”

“…In our opinion, total preservation time represents an overly cautious way to compare outcomes of cold stored versus NMP grafts, as it assumes that cumulative injury over time is similar with both modalities; this is hard for us to accept for metabolically functional livers actively producing bile ex vivo. Matching storage duration in both modalities would be difficult because livers require at least 4-6 h to stabilize during the NMP phase (3)(4)(5). Although extended NMP duration should be monitored closely in ongoing safety trials, accrued porcine and limited pilot clinical experience suggests that NMP duration is not a critical variable, especially when kept ≤24 h (4).…”

Normothermic Ex Vivo Kidney Perfusion Following Static Cold Storage—Brief, Intermediate, or Prolonged Perfusion for Optimal Renal Graft Reconditioning?

“…In contrast, normothermic ex vivo liver perfusion has recently been introduced into clinical practice investigating continuous NMP with near complete exclusion of SCS. The initial clinical studies demonstrated feasibility and safety (12,13).…”