Reply

Liver Transplantation, vol. 27, pp. 602–603

Abstract

Potential conflict of interest: Nothing to report. TO THE EDITOR: We thank Hann et al. for their kind interest in our initial experience with the normothermic machine preservation (NMP) of liver allografts using a back‐to‐base approach. The technique has enabled a safe expansion of our donor pool through the objective assessment of orphan grafts, often procured at distant sites, before committing to implantation. Furthermore, in comparison to traditional static cold storage, back‐to‐base NMP has also provided major logistical benefits because of its independence from recipient variables. For example, it has facilitated the use of grafts donated after circulatory death (DCD) for retransplantation with the safety of having the donor organ preserved under optimal conditions during a difficult hepatectomy. The next exciting frontiers in NMP are the use of marginal grafts in high‐risk recipients, as outlined by Hann et al., and novel therapeutic interventions to resuscitate otherwise unsalvageable grafts. However, before these indications can develop further, it is essential to more precisely define exactly which ex situ parameters determine graft viability. Lactate clearance was arguably the earliest of the proposed viability criteria, with levels below 2.5 mmol/L most often observed in viable grafts by the 2‐hour mark. Furthermore, it has been clearly demonstrated that refractory serum lactate concentrations during NMP are a strong indicator of nonviability.(1) Unfortunately, however, it is also true that lactate clearance below the defined cutoff of 2.5 mmol/L can still result in primary nonfunction in the recipient (albeit under different NMP conditions),(2) such that ex vivo lactate clearance might still be observed in the presence of minimal and overall inadequate hepatocellular function. Nevertheless, we acknowledge the proposal of Hann et al. to increase graft utility by delaying the measurement of the lactate clearance cutoff of 2.5 mmol/L from 2 to 4 hours, as proven by their recent viability testing and transplantation of marginal livers (VITTAL) trial results.(3) In contrast to the experience of Hann et al., and despite early technical issues with bile collection, we have experienced no problems since routine ligation of the cystic duct. Although Hann et al. rightly debate the value of bile production as a major indicator of parenchymal function during NMP, we continue to use biliary biomarkers as essential measures of cholangiocyte viability when considering the use of DCD grafts. In our ongoing experience, we have increasingly focused on NMP for orphan DCD livers as opposed to those procured from brain‐dead donors, and because of this the prevention of ischemic cholangiopathy continues to be at the forefront of our thinking in terms of overall viability assessment. The use of 20% glucose solution instead of parenteral nutrition containing amino acids is interesting, and we are not aware of any direct comparisons between the 2 different strategies. Empirical evidence in vitro has shown halted hepatocyte regeneration in the absence of amino acid provision(4); however, the actual clinical impact of amino acid infusion during NMP is still to be elucidated. Although the understanding of viability markers continues to develop, individual centers must assess the acceptable level of risk to their population, as defined by attrition on the waiting list, and also the availability of urgent grafts for salvage retransplant. In Queensland, waiting list attrition is low and access to salvage grafts is restricted by population size, such that a relaxation of viability measures in our practice is currently both unnecessary and unacceptable.

Authors 10

1. Janske Reiling corresponding

   The University of Queensland · Greenslopes Private Hospital · Princess Alexandra Hospital · Maastricht University

   Affiliation as printed

   Department of Surgery,School of Nutrition and Translational Research in Metabolism,Maastricht University,Maastricht,the Netherlands

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

   Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

   Princess Alexandra Research Foundation,Princess Alexandra Hospital,Brisbane,Queensland,Australia

   Queensland Liver Transplant Service,Princess Alexandra Hospital,Brisbane,Queensland,Australia

2. Nick Butler

   The University of Queensland · Maastricht University

   Affiliation as printed

   Department of Surgery,School of Nutrition and Translational Research in Metabolism,Maastricht University,Maastricht,the Netherlands

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

3. Andrew H. Simpson

   Princess Alexandra Hospital

   Affiliation as printed

   Visiting Medical Officer Perfusion,Department of Cardiac Anesthetics,Princess Alexandra Hospital,Brisbane,Queensland,Australia

4. David S. R. Lockwood

   The University of Queensland · Maastricht University

   Affiliation as printed

   Department of Surgery,School of Nutrition and Translational Research in Metabolism,Maastricht University,Maastricht,the Netherlands

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

5. Kim R. Bridle

   The University of Queensland · Greenslopes Private Hospital

   Affiliation as printed

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

   Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

6. Nishreen Santrampurwala

   The University of Queensland · Greenslopes Private Hospital

   Affiliation as printed

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

   Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

7. Laurence J. Britton

   The University of Queensland · Greenslopes Private Hospital · Princess Alexandra Hospital · Maastricht University

   Affiliation as printed

   Department of Gastroenterology,Princess Alexandra Hospital,Brisbane,Queensland,Australia

   Department of Surgery,School of Nutrition and Translational Research in Metabolism,Maastricht University,Maastricht,the Netherlands

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

   Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

8. Dorothy H. Crawford

   The University of Queensland · Greenslopes Private Hospital

   Affiliation as printed

   Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

   Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

9. Cornelius H.C. Dejong Aachen Department of Surgery

   Princess Alexandra Hospital · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Surgery,Universitätsklinikum Aachen,Aachen,Germany

   Queensland Liver Transplant Service,Princess Alexandra Hospital,Brisbane,Queensland,Australia

10. Jonathan Fawcett

    The University of Queensland · Greenslopes Private Hospital · Princess Alexandra Hospital · Maastricht University

    Affiliation as printed

    Department of Surgery,School of Nutrition and Translational Research in Metabolism,Maastricht University,Maastricht,the Netherlands

    Faculty of Medicine,The University of Queensland,Brisbane,Queensland,Australia

    Gallipoli Medical Research Institute,Greenslopes Private Hospital,Brisbane,Queensland,Australia

    Princess Alexandra Research Foundation,Princess Alexandra Hospital,Brisbane,Queensland,Australia