Anita Niu

Introduction: Long‐term normothermic machine perfusion (LT‐NMP) enables the assessment and optimization of livers for days and, potentially, weeks. However, models of LT‐NMP have only been described for human and pig livers, which are resource intensive and impractical for laboratory research. Cost‐effective small animal models of LT‐NMP are needed for future research. This study aimed to develop a system for LT‐NMP of rat livers for up to 72 h. Methods: This study was performed in two stages: the development phase ( n = 20) and validation phase ( n = 5). The perfusion system included an organ reservoir, pump, heat exchanger, long‐term oxygenator, and dialysis. Hormonal and nutritional support were continuously infused. During the validation phase, five consecutive grafts were perfused using our protocol. At 72 h postreperfusion, grafts were assessed for viability, which was based on hemodynamic stability, mitochondrial function, bile production, and metabolic activity. Results: Rodent livers were supported up to 107 h using our LT‐NMP protocol. All grafts in the validation phase remained viable at 72 h ( n = 5/5). The median oxygen consumption and bile production at 72 h were 0.079 mLO ₂ /min/g‐liver and 8.6 uL/h/g‐liver, respectively. All grafts had a systemic vascular resistance less than 0.25 mmHg/mL/min. Metabolic activity, defined as lactate clearance, glucose production, or response to glucagon, was observed in all grafts (5/5). Conclusions: This is the first study to report LT‐NMP of rodent livers up to 5 days. Using our protocol, rat livers could reliably be supported until 72 h. This model provides a greater opportunity to investigate novel therapeutics to assess, optimize, and regenerate liver grafts for transplantation.

Background: Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high‐risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts.Methods: This study includes all papers comparing HOPE to static cold storage for high‐risk ECD and DCDD grafts. Systematic searches of Medline, Embase, and Scopus were completed using the terms “HOPE” OR “hypothermic oxygenated machine perfusion” AND “liver transplantation”. Data were extracted and analyzed using IBM SPSS to perform the meta‐analysis.Results: A total of 2286 records were identified, with 10 meeting the inclusion criteria. Overall, the quality of evidence is heterogenous with many papers relying on retrospective controls. However, pooled analysis demonstrates HOPE to significantly reduce the rate of early allograft dysfunction, 12‐month graft failure, re‐transplantation, total biliary complications, and non‐anastomotic strictures for high‐risk grafts.Conclusions: There is good evidence that HOPE improves outcomes following liver transplantation across a number of biochemical and clinical endpoints for high‐risk grafts. Of note, the reduction in biliary complications and re‐transplantation is particularly significant given the morbidity associated with these endpoints. However, further, high‐quality prospective trials with contemporary controls and clinically relevant primary endpoints are needed to better define the impact of HOPE for this cohort of grafts.