Assessment and Transplantation of Orphan Donor Livers: A Back‐to‐Base Approach to Normothermic Machine Perfusion

Abstract

Globally, a large proportion of donor livers are discarded due to concerns over inadequate organ quality. Normothermic machine perfusion (NMP) allows for hepatocellular and biliary viability assessment prior to transplantation and might therefore enable the safe use of these orphan donor livers. We describe here the first Australasian experience of NMP-preserved liver transplants using a 'backto-base' approach, where NMP was commenced at the recipient hospital following initial static cold storage. In the preclinical phase, 10 human donor livers declined for transplantation (7 from donation after circulatory death [DCD] and 3 from donation after brain death [DBD]) were perfused using a custom-made NMP setup. Subsequently, 10 orphan donor livers (5 from DCD and 5 from DBD) underwent NMP and viability assessment on the OrganOx metra device (OrganOx Limited, Oxford, United Kingdom). Both hepatocellular and biliary viability criteria were used. The median donor risk index was 1.53 (1.16-1.71), and the median recipient Model for End-Stage Liver Disease score was 17 (11-21). In the preclinical phase, 'back-to-base' NMP was deemed suitable and feasible. In the clinical phase, each graft met predefined criteria for implantation during NMP and was subsequently transplanted. Five (50%) recipients developed early allograft dysfunction based on peak aspartate aminotransferase. To date, all grafts function satisfactorily, and none of the 5 recipients who received a DCD liver have developed cholangiopathy. The OrganOx metra using a backto-base approach has enabled the safe use of 10 high-risk orphan donor livers with 100% 6-month patient and graft survival. NMP improved surgeon confidence to use orphan donor livers and has enabled a safe expansion of the donor pool.

The Rise of the Machines: Will They Fulfill the Restoration Promise?

“…Reiling et al (4) 17 (14-26) 50% EAD, all grafts functioning, no DCD cholangiopathy Nasralla et al (5) Mergental et al (6) Bral et al (9) Schlegel et al (7) (2019) Viability Testing and Transplantation of Marginal Livers (VITTAL) trial by Mergental et al (6) did use NMP to monitor and revitalize discarded livers in the United Kingdom. EAD occurred in 32% of patients with 86% allograft survival at 1 year.…”

Viability Assessment in Liver Transplantation—What Is the Impact of Dynamic Organ Preservation?

“…Routine blood gas or biochemical analysis were transferred into the field of organ preservation and have been performed either from the cold storage solution or machine perfusates [10,[57][58][59]. The majority of markers is however unspecific, being copied from clinical practice of patients with liver diseases, including for example pH, lactate, or liver transaminases.…”

“…Normothermic machine perfusion (NMP) is nominated by many as the best perfusion approach to assess organ viability [59,73]. Various authors claim this technology provides "near-physiological" conditions, although the question, what circumstances from organ donation, transport and transplantation are really physiological?…”

“…High resistance has been a sign of organ injury and later dysfunction. Stable perfusion flow rates during NMP were therefore suggested by many [22,59,60]. A few authors have defined more specific viability criteria with a portal vein and hepatic artery flow above >500 mL/min and >150 mL/min, respectively (Table 2) [9,57,74].…”

Necroptosis in Hepatosteatotic Ischaemia-Reperfusion Injury

“…NMP aims to minimise the IR injury in liver graft and improve preservation of ECD livers [ 235 ]. The successful use of NMP in liver transplantation of ECD livers provides the opportunity for therapeutic intervention prior to transplantation of ECD livers [ 236 ]. NMP not only easily facilitates addition of therapeutic agents, such as necroptosis inhibitors described above, to the perfusion system but allows assessment of hepatocellular function and injury prior to transplantation.…”