Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof‐of‐concept study using discarded human livers

Abstract

The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk livers is the development of objective criteria for assessing their condition before transplantation. Compared to simple cold storage, hypothermic machine perfusion (HMP) provides a unique window for evaluating liver grafts between procurement and transplantation. In this proof-of-concept study, we tested basic parameters during HMP that may reflect the condition of human liver grafts, and we assessed their morphology after prolonged HMP. Seventeen discarded human livers were machine-perfused. Eleven livers were nontransplantable (major absolute contraindications and severe macrovesicular steatosis in the majority of the cases). Six livers were found in retrospect to be transplantable but could not be allocated and served as controls. Metabolic parameters (pH, lactate, partial pressure of oxygen, and partial pressure of carbon dioxide), enzyme release in the perfusate [aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)], and arterial/portal resistances were monitored during HMP. Nontransplantable livers released more AST and LDH than transplantable livers. In contrast, arterial/portal vascular resistances and metabolic profiles did not differ between the 2 groups. Morphologically, transplantable

Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

“…However, although hypothermic perfusion has achieved adequate results in near-clinical and clinical setting (3,4), its use seems to offer too little protection in suboptimal grafts (5,6). An important advantage of normothermic perfusion (37…”

Graft Reconditioning before Liver Transplantation

“…No morphological differences were found [46]. In discarded steatotic grafts cold-stored for 13 h before initiation of HMP, an increased release of AST and LDH into the perfusate but similar vascular resistances and metabolic profiles in comparison with transplantable human livers were noted [47]. …”

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation

“…Different liver retrieval techniques for DCD have been described in the early nineties, including femoral cannulation prior to withdrawal of life support, and to as the ''super-rapid technique'' [74]. The extent of ischemia reperfusion injury depends on the degree of activation of key players involved in the hepatic ischemia reperfusion injury including Kupffer cells, platelets and leukocytes, besides the generated pro-inflammatory response (oxidative stress, inflammatory cytokines, and cytoplasmic proteases, up regulation of pro-inflammatory transcription factors).…”

“…lazaroids (iron-dependent lipid peroxidase inhibitor), N-acetyl-cysteine were also studied in animal models [26]. Perhaps the most effective step in organ preservation is the cooling of the organ as the metabolic rate is halved for every 10 C drop in temperature [74].…”

“…They used HMP as a screening-tool to distinguish transplantable from non-transplantable ECD human liver grafts that were rejected for LT [74]. With SCS, the sinusoids become constricted due to the hypothermia, which prevents the penetration of the preservation solution in to the tissues and may cause an impaired microcirculation upon reperfusion [85].…”