A Back‐to‐Base Experience of Human Normothermic Ex Situ Liver Perfusion: Does the Chill Kill?

Abstract

Normothermic machine perfusion (NMP) has been shown to protect livers from injury between procurement and transplantation in a randomized controlled trial, where the machine was transported to and from the donor center. The aim of this study was to determine whether an alternative, more practical back‐to‐base approach after initial static cold storage would compromise beneficial outcomes. Between February 2015 and June 2018, a nonrandomized pilot study was performed at a single site. Outcomes of back‐to‐base livers (n = 26) were compared with those of grafts procured locally that underwent immediate NMP (n = 17). The primary outcome measure (safety) was defined as 30‐day patient and graft survival. A total of 46 liver grafts were perfused with NMP, of which 3 were discarded based on poor ex situ perfusion function. The 30‐day patient and graft survival in the back‐to‐base and local NMP groups were both 100% (primary outcome: safety). Despite significantly prolonged mean cold ischemia time (6 versus 3.2 hours; P = 0.001), the back‐to‐base livers demonstrated no difference in graft function, incidence of complications, or graft and patient survival. In conclusion, the back‐to‐base approach was safe, did not compromise the overall benefit of NMP, and offers a practical alternative to portable normothermic ex situ machine transport.

Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review

“…Following the Consortium for Organ Preservation in Europe (COPE) international clinical trial of NMP for liver transplantation, we found that immune-mediated processes were found to be positively impacted by NMP (e.g., reduced PRS in NMP cohort) corroborating pre-clinical work previously conducted within the group [12,14,31]. Furthermore, subsequent clinical studies exploring the use of NMP following longer periods of cold preservation in both North America and Europe have shown favourable outcomes for NMP with respect to leucocytosis and inflammatory cell infiltrates histologically [15,32]. Mechanistically, this has been explored by Jassem et al (2018), where the group found that the proportion of tissue-resident CD4 pos CD25 high CD127 neg FOXP3 pos regulatory T cells (Treg) seems to increase through the course of NMP, with more interferon-gamma (IFN-γ) and interleukin 17-producing T cells present and less necrosis and apoptosis in the liver parenchyma, associated with less neutrophil infiltration compared to SCS livers [33].…”

Machine Perfusions in Liver Transplantation: The Evidence‐Based Position Paper of the Italian Society of Organ and Tissue Transplantation

“…(31) Two further articles comparing different NMP modalities reported an ITBL rate of 2.7%. (27,33) recOMMenDatiOn We suggest that considering the use of NMP for the reduction of posttransplant ITBLs is not supported by the evidence available in literature. (2B)…”

“…A total of 34 LTs of grafts not producing bile during NMP have been reported (27)(28)(29)31,33,50) leading to 1 graft failure for hepatic artery thrombosis and 1 death for hepatitis C virus recurrence and rejection. Bile pH was measured in only 1 RCT, (38) but it was not the primary study endpoint.…”

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

“…This is in line with recent studies showing comparable outcomes with post-SCS NMP versus transit NMP. (5,6) Consensus on viability criteria during NMP is yet to be achieved, which is of most importance when using the technique to combat high nonuse rates. Lactate clearance, as a surrogate marker of metabolic recovery, has long been seen as an attractive viability marker because it is easy and reliable to serially assess.…”

“…Therefore, a back-to-base approach with the initiation of NMP at the recipient hospital could be a suitable and less complicated alternative, particularly for transplant services operating over large geographical areas. (5,6) To date, NMP has mostly been used as an alternative preservation method for livers already accepted for transplantation. (7) However, to combat high discard rates, more livers declined for transplantation should undergo functional assessment because a proportion are likely suitable for transplantation.…”