Establishing a Platform for 1-Wk Normothermic Machine Perfusion of Donor Livers

Background. Although short-term (24 h) normothermic machine perfusion (NMP) is suitable to assess liver quality before transplantation, prolonged NMP offers the potential for modification, regeneration, and repair of marginal organs. We systematically aimed for the development of a reproducible perfusion protocol for long-term ex situ liver preservation (LTP), using a commercially available perfusion device without hardware modification. Methods. Livers retrieved from domestic pigs (N = 18) were perfused for up to 7 d (OrganOx Metra). A precision-cut liver slice culture model was applied to assess and determine the perfusate recipe. The perfusion protocol was assessed and validated in a stepwise process and later evaluated in nontransplanted human livers (N = 22). Results. The stepwise development using porcine livers finally resulted in 7-d perfusion with stable function and preserved morphology. Key advancements include red blood cell substitution, bile excretion modifications, and expanded antiinfective therapy. Applying the perfusion protocol in nontransplantable human donor livers enabled 7-d NMP in 4 livers, while control livers deteriorated after 66 [48–84] h NMP. Preserved bile production, low-levels of free hemoglobin and a low-degree of inflammation were identified as key factors for successful LTP. Conclusions. Seven-day preservation of porcine and human livers using the LTP protocol in an unmodified, commercial perfusion system is feasible; thus, the model system is suitable for treating and recovering livers, which may help to limit global organ shortage.