Abstract
BackgroundWhile growing evidence supports the use of hypothermic oxygenated machine perfusion (HOPE) in liver transplantation, its effects on liver metabolism are still incompletely understood.MethodsTo assess liver metabolism during HOPE using microdialysis (MD), we conducted an open‐label, observational pilot study on 10 consecutive grafts treated with dual‐HOPE (D‐HOPE). Microdialysate and perfusate levels of glucose, lactate, pyruvate, glutamate, and flavin mononucleotide (FMN) were measured during back table preparation and D‐HOPE and correlated to graft function and patient outcome.ResultsMedian (IQR) MD and D‐HOPE time was 228 (210, 245) and 116 (103, 143) min. Three grafts developed early allograft dysfunction (EAD), with one requiring retransplantation. During D‐HOPE, MD glucose and lactate levels increased (ANOVA = 9.88 [p = 0.01] and 3.71 [p = 0.08]). Their 2nd‐hour levels were higher in EAD group and positively correlated with L‐GrAFT score. 2nd‐hour MD glucose and lactate were also positively correlated with cold ischemia time, macrovesicular steatosis, weight gain during D‐HOPE, and perfusate FMN. These correlations were not apparent when perfusate levels were considered. In contrast, MD FMN levels invariably dropped steeply after D‐HOPE start, whereas perfusate FMN was higher in dysfunctioning grafts.ConclusionMD glucose and lactate during D‐HOPE are markers of hepatocellular injury and could represent additional elements of the viability assessment.
Highlights
Hypothermic oxygenated machine perfusion (HOPE) is gaining increasing interest as a tool to reduce ischemia- reperfusion injury and to improve outcomes of liver transplantation (LT)
hypothermic oxygenated machine perfusion (HOPE) use has been associated with improved outcomes of grafts from donors after circulatory death (DCD),1–3 extended- criteria donors after brain death (DBD)[4,5], and steatotic grafts.[6]
MD has been extensively used in a variety of settings, especially for bedside sampling of cerebral interstitial fluid in critically ill patients.13–17 In LT, MD has been used to assess liver metabolism during the phases of liver retrieval, cold preservation and after graft implantation,18–22 and explored as a tool for early detection of ischemic complications and acute rejection.23–29 As applied to machine perfusion, MD has the potential of allowing monitoring of liver metabolism throughout static cold storage (SCS) and HOPE, overcoming one limitation of perfusate analysis, which cannot assess metabolism during SCS
Summary
Hypothermic oxygenated machine perfusion (HOPE) is gaining increasing interest as a tool to reduce ischemia- reperfusion injury and to improve outcomes of liver transplantation (LT). MD has been extensively used in a variety of settings, especially for bedside sampling of cerebral interstitial fluid in critically ill patients.13–17 In LT, MD has been used to assess liver metabolism during the phases of liver retrieval, cold preservation and after graft implantation,18–22 and explored as a tool for early detection of ischemic complications and acute rejection.23–29 As applied to machine perfusion, MD has the potential of allowing monitoring of liver metabolism throughout SCS and HOPE, overcoming one limitation of perfusate analysis, which cannot assess metabolism during SCS.
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