Letter to Editor: Repair or Prevent: What Is the Real Impact of Normothermic Machine Perfusion in Liver Transplantation?

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the paper by Jassem et al.,1 which provides detailed gene expression profiles of human livers during normothermic machine perfusion (NMP), compared with conventional cold storage. The authors should be congratulated on this extensive analysis, which shows for the first time transcriptional changes during any form of reperfusion under normothermic conditions.1 However, we would like to add a few critical comments. The authors analyzed liver samples at the end of cold storage or NMP, and after graft implantation. First, although changes in gene alteration during NMP are certainly relevant, we would like to mention that all livers in the NMP group underwent prolonged normothermic reperfusion on the device before the first biopsy, obtained after a considerable contact of liver cells with fully oxygenated blood. Another biopsy, for example, 1 hour after the start of NMP, would be important to confirm the hypothesis that NMP is in fact actively leading to down‐regulation of inflammatory pathways (Fig. 1). Importantly, for kidneys, lungs, hearts, and livers, current research has shown the opposite.2 Second, proper comparisons of NMP and cold storage require assessment of reperfusion injury after a similar duration of normothermic reperfusion, either on the NMP device or after reperfusion of cold stored livers in situ.1 (Fig. 1) Expectedly, gene expression profiles between NMP and cold storage appear very different, and parallel previous assessments after transplantation of subnormothermically perfused livers.4 Third, the results imply that NMP after cold ischemia triggers inferior outcome.1 Consistently, Watson et al. have demonstrated a clear inflammatory response when NMP was performed after significant cold storage in livers with a cumulative high risk.5 It may therefore be important to emphasize that especially high‐risk livers need either upfront NMP or other machine perfusion techniques targeting metabolic changes before implantation, such as hypothermic oxygenated perfusion or controlled oxygenated rewarming.2Figure 1: Overview of liver preservation and timepoints of gene expression profile analysis comparing upfront normothermic machine perfusion and cold storage.Based on this, we believe that the presented data show a minimization of inflammation and necrosis through replacement of cold ischemia by sophisticated NMP techniques. However, we do not think the data support the conclusion that NMP itself leads to down‐regulations of inflammatory pathways.