Normothermic Acellular Ex Vivo Liver Perfusion Reduces Liver and Bile Duct Injury of Pig Livers Retrieved After Cardiac Death

Boehnert, Markus; Yeung, Jonathan C.; Bazerbachi, Fateh; Knaak, J. M.; Selzner, Nazia; McGilvray, Ian; Rotstein, Ori D.; Adeyi, Oyedele; Kandel, Sonja; Rogalla, Patrik; Yip, Paul; Levy, Gary; Keshavjee, Shaf; Grant, David; Selzner, Markus

doi:10.1111/ajt.12224

Cited by 110 publications

(117 citation statements)

References 30 publications

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“…Experimental data from large animal studies, specifically investigating biliary epithelial recovery following a period of warm ischemic and NMP, suggest that warm oxygen delivery may provide a critical advantage (29,30). This is a key issue in the quest to increase the utilization of DCD organs in liver transplantation and will only be addressed in the context of a randomized trial with longer-term follow-up of patients.…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

420

412

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Joint first authors. ISRCTN 14355416.The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group ) versus , p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.Abbreviations: AST, aspartate transaminase; DBD, donation after brain death; DCD, donation after circulatory death; IRI, ischemia-reperfusion injury; IVC, inferior vena cava; MELD, model for end-stage liver disease; NHSBT, National Health Service Blood and Transplant; NMP, normothermic machine perfusion

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Section: Discussionmentioning

confidence: 99%

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Ravikumar

Jassem

Mergental

et al. 2016

American Journal of Transplantation

420

412

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“…Normothermic machine perfusion (NMP) is a preservation technology with potential to prevent both ischemic injury and the deleterious effect of cold temperatures by perfusing organs with a warm oxygenated perfusion solution. Numerous studies have demonstrated the advantage of NMP over CS in the preservation of DCD livers (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), suggesting that NMP may greatly benefit the practice of liver transplantation. conducted using whole blood (WB) (9)(10)(11)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death

Liu

Nassar

Farias

et al. 2016

American Journal of Transplantation

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The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

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“…60 Normothermic machine perfusion was also shown to reduce liver and bile duct injury in a porcine DCD liver model. 61 Recovery of DCD livers and successful transplant after an extended WIT has also been recorded in rat models. 62 Rat livers subjected to 45 minutes of warm ischemia and 2 hours of cold storage were suc cessfully recovered using normothermic machine perfusion and transplanted.…”

Section: Future Considerationsmentioning

confidence: 92%

Untitled

2016

Exp Clin Transplant

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The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.

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Normothermic Acellular Ex Vivo Liver Perfusion Reduces Liver and Bile Duct Injury of Pig Livers Retrieved After Cardiac Death

Cited by 110 publications

References 30 publications

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial

Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death

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