Beneficial effects of end-ischemic oxygenated machine perfusion preservation for split-liver transplantation in recovering graft function and reducing ischemia–reperfusion injury

Abstract

This study examined the efficacy of end-ischemic hypothermic oxygenated machine perfusion preservation (HOPE) using an originally developed machine perfusion system for split-liver transplantation. Porcine split-liver grafts were created via 75% liver resection after 10 min of warm ischemia. In Group 1, grafts were preserved by simple cold storage (CS) for 8 h (CS group; n = 4). In Group 2, grafts were preserved by simple CS for 6 h and end-ischemic HOPE for 2 h (HOPE group; n = 5). All grafts were evaluated using an isolated ex vivo reperfusion model with autologous blood for 2 h. Biochemical markers (aspartate aminotransferase and lactate dehydrogenase levels) were significantly better immediately after reperfusion in the HOPE group than in the CS group. Furthermore, the HOPE group had a better histological score. The levels of inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-10) were significantly lower after reperfusion in the HOPE group. Therefore, we concluded that end-ischemic HOPE for split-liver transplantation can aid in recovering the graft function and reducing ischemia–reperfusion injury. HOPE, using our originally developed machine perfusion system, is safe and can improve graft function while attenuating liver injury due to preservation.

Liver transplantation of partial grafts after ex situ splitting during hypothermic oxygenated perfusion—The HOPE–Split pilot study

“…Preservation with HOPE has already been shown to be beneficial, especially in the setting of marginal whole grafts by mitigating mitochondrial damage [10] and reducing sterile inflammation upon reperfusion. [27][28][29] In line with these observations, we were able to show a reduction in lobular neutrophilic infiltrate and the absence of severe IRI scores on reperfusion biopsies of HOPE-Split grafts compared with the Static-Split grafts. Of note, all HOPE-Split grafts underwent perfusion for >1 h (158 min in adult recipients and 95 min in pediatric recipients), which has been shown to be sufficient to mitigate IRI.…”

“…[10,25] This leads to a mitigation of IRI upon implantation of the graft and translates into clinical benefits compared with static cold storage, as shown by recent randomized clinical trials. [7,8] However, data on the use of HOPE in split LT are limited to small case series in either experimental [26,27] or clinical [12][13][14] settings. Previous reports from Spada et al [12] and Thorne et al [14] presented technical aspects of the procedure in single cases.…”

Over 30 Years of Pediatric Liver Transplantation at the Charité—Universitätsmedizin Berlin

“…Reports detailing early allograft dysfunction for pediatric patients are lacking. However, we assume more complex vascular anastomosis resulting in potentially longer cold and warm ischemia times, respectively, to lead, at least in part, to higher EAD rates than in adult patients [39][40][41]. Nonetheless overall re-transplantation rates remained comparatively low, potentially indicating recuperation in selected patients.…”

Effect of Mechanical Perfusion on Ischemia-reperfusion Injury after Liver Transplantation

“…Mechanical perfusion can effectively control the level of inflammatory factors in the early stage after liver transplantation, so as to alleviate the degree of ischemia-reperfusion injury caused by it. Static cold preserved by low temperature control after the donor liver in vitro tissue metabolism and nutrient consumption, but not to inhibit [21] of this process, therefore in the process of save for metabolism of liver is still in a constant state, and the state of ischemia hypoxia increases based energy metabolism level, restore perfusion after liver transplantation the metabolic situation exacerbate. As a result, the balance of oxygen free radicals is broken and a large number of free radicals are generated, thereby aggravating inflammatory changes and affecting the effect of liver transplantation.…”