Machine Perfusion—Leaving Its Mark on Liver Transplantation

Abstract

Despite rationing access to the liver transplantation waiting list, there is a significant disparity between the number of recipients requiring transplantation and the number of donor organs available.1 This leads to a significant waiting list mortality, which has driven increased utilization of “high risk” (marginal) grafts. Here, the increased risk to the recipient’s life using a less optimal donor organ has to be weighed against the risk of death on the waiting list whilst waiting for a more “optimal” graft.2 Normothermic ex situ liver perfusion (NESLiP) has emerged as a promising technique to allow assessment of the viability and safety of transplanting these marginal donor livers.3 NESLiP involves placing the donor liver in a container with its anterior surface cradled in a plastic basket, while perfusing both the artery and portal vein with oxygenated blood. We started a clinical program of ex situ machine perfusion in our center in 2014 and have used 2 devices: Liver Assist device (Organ Assist, Groningen, The Netherlands) and metra (OrganOx, Oxford, United Kingdom). We perfused 58 livers on the Liver Assist, most of which had been declined for transplantation by all other centers in the United Kingdom; of these 22 were successfully transplanted. Subsequently, we have used the metra (OrganOx) to perfuse 116 livers and 90 of these were transplanted. Here, we provide the first report of a complication that we have termed “cradle sign”: compression injury to the liver parenchyma as a consequence of its positioning against the plastic basket during machine perfusion (Figure 1). This only becomes evident at the end of perfusion when the liver is removed from the perfusion device. We estimate that this phenomenon has occurred in <5% of perfused livers at our center and was common to both of the devices that we have used (Liver Assist and OrganOx metra).FIGURE 1.: Cradle sign following NESLiP. A, Cradle sign on a liver following NESLiP on Liver Assist that was previously declined by all UK liver centers and used to evaluate markers of viability. This liver was not transplanted clinically because of adverse performance during perfusion. B, Appearances of liver on arrival at center after period of cold storage, demonstrating moderate steatosis macroscopically (left) and as liver was being taken off NESLiP (on Liver Assist) before transplantation demonstrating cradle sign (middle). Initial graft function was good with no evidence of early allograft dysfunction and a model of early allograft function score of 5.2.4 , 5 Additional details about donor and recipient are included in Table S1 (SDC, https://links.lww.com/TP/C18). Volume rendered 3-dimensional and axial computed tomography images at d 17 posttransplantation, demonstrating persistence of the latticed appearance of cradle sign (right). Currently, graft function remains good over 2 y after transplantation. Written patient consent was obtained, and this article is exempt from approval from an ethics’ board. NESLiP, normothermic ex situ liver perfusion.Although cradle sign may look alarming, in our experience these livers can be successfully transplanted if the other parameters of viability are favorable,3 albeit that the effects remain visible on computed tomography (Figure 1). It is currently not possible to completely see the anterior side of the liver after machine perfusion has started and so one cannot see the development of cradle sign until the point at which the liver is taken off the machine for implantation. One can envisage that the incidence of cradle sign could be reduced by the use of pressure redistribution technology or adoption of a policy of frequent repositioning, although that may affect flows within the vessels and/or compromise sterility. Although we have seen no significant adverse effect on the recipients at our center, our observation does mean that without improvement in the device design or perfusion protocols, it may limit the use of NESLiP in terms of prolonged perfusion especially in heavier or steatotic grafts. CONLUSIONS Although “cradle sign” may well look alarming, if the viability parameters are otherwise favorable, then our experience to date suggests that these livers can be successfully transplanted.

Topics & Concepts