26-hour Storage of a Declined Liver Before Successful Transplantation Using Ex Vivo Normothermic Perfusion

Watson, Chris; Randle, Lucy V.; Kosmoliaptsis, Vasilis; Gibbs, Paul; Allison, Michael; Butler, Andrew

doi:10.1097/sla.0000000000001834

Cited by 45 publications

(42 citation statements)

References 4 publications

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“…The trial met its primary outcome, demonstrating a significant reduction in recipient peak serum aspartate aminotransferase (AST) in the NMP group (a surrogate marker for long term patient and graft survival ). The improvement in early biochemical function in NMP livers was in the context of significantly longer preservation times; indeed one of the benefits of NMP is extended graft preservation . As with the kidney, prolonged preservation could improve operating room logistics and may also provide the potential to provide liver‐directed therapeutic interventions to further enhance the graft during preservation.…”

Section: Perfusion and Re‐conditioning Methods For Abdominal Organsmentioning

confidence: 93%

The future of organ perfusion and re‐conditioning

et al. 2019

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Summary Organ preservation and re‐conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization and improved initial graft function. Here, we summarize the latest findings and study the results of ex‐vivo/ex‐situ hypothermic (HMP) and normothermic machine perfusion (NMP) in the area of abdominal organ transplantation (kidney, liver, pancreas and intestine). We also consider the potential role of normothermic regional perfusion (NRP) to re‐condition donors after circulatory death organs before retrieval. The findings from clinical studies reported to date suggest that machine perfusion will offer real benefits when compared with conventional cold preservation. Several randomized trials are expected to report their findings within the next 2 years which may shed light on the relative merits of different perfusion methods and could indicate which perfusion parameters may be most useful to predict organ quality and viability. Further work is needed to identify composite endpoints that are relevant for transplanted organs that have undergone machine preservation. Multi‐centre trials to compare and analyse the combinations of NRP followed by HMP and/or NMP, either directly after organ retrieval using transportable devices or when back‐to‐base, are needed. The potential applications of machine preservation technology beyond the field of solid organ transplantation are also considered.

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Section: Perfusion and Re‐conditioning Methods For Abdominal Organsmentioning

confidence: 93%

The future of organ perfusion and re‐conditioning

et al. 2019

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“…Several groups, including that of the authors, have reported recently on the feasibility and potential benefits of end‐ischaemic normothermic machine perfusion of human donor livers. In contrast to hypothermic machine perfusion, normothermic liver perfusion enables an ex situ functional assessment.…”

Section: Discussionmentioning

confidence: 99%

Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death

Rijn

Karimian

Matton

et al. 2017

British Journal of Surgery

206

239

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BackgroundExperimental studies have suggested that end‐ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case–control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation.MethodsIn consecutive DCD liver transplantations, liver grafts were treated with end‐ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End‐stage Liver Disease (MELD) score. All patients were followed for 1 year.ResultsTen transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6‐month and 1‐year graft and patient survival rates were 100 per cent in the DHOPE group. Six‐month graft survival and 1‐year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5′‐triphosphate (ATP) content increased 11‐fold, from 6 (3–10) to 66 (42–87) µmol per g protein (P = 0·005). All DHOPE‐preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7–1·4) versus 2·6 (0·9–5·1) mg/dl, P = 0·044). None of the ten DHOPE‐preserved livers required retransplantation for non‐anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140).ConclusionThis clinical study of end‐ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post‐transplant biliary complications.

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“…Preclinical studies have demonstrated that NMP provides superior preservation for livers from donation after circulatory death (DCD) compared with CS . In recent years, this technology has transitioned to the perfusion of discarded human livers and clinical trials . Another potential advantage of NMP is the ability to change steatosis.…”

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confidence: 99%

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion

et al. 2018

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Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

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26-hour Storage of a Declined Liver Before Successful Transplantation Using Ex Vivo Normothermic Perfusion

Cited by 45 publications

References 4 publications

The future of organ perfusion and re‐conditioning

The future of organ perfusion and re‐conditioning

Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion

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