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      Hypothermic machine perfusion reduces the incidences of early allograft dysfunction and biliary complications and improves 1-year graft survival after human liver transplantation : A meta-analysis

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          Abstract

          Background:

          The worldwide organ shortage continues to be the main limitation of liver transplantation. To bridge the gap between the demand and supply of liver grafts, it becomes necessary to use extended criteria donor livers for transplantation. Hypothermic machine perfusion (HMP) is designed to improve the quality of preserved organs before implantation. In clinical liver transplantation, HMP is still in its infancy.

          Methods:

          A systematic search of the PubMed, EMBASE, Springer, and Cochrane Library databases was performed to identify studies comparing the outcomes in patients with HMP versus static cold storage (SCS) of liver grafts. The parameters analyzed included the incidences of primary nonfunction (PNF), early allograft dysfunction (EAD), vascular complications, biliary complications, length of hospital stay, and 1-year graft survival.

          Results:

          A total of 6 studies qualified for the review, involving 144 and 178 liver grafts with HMP or SCS preservation, respectively. The incidences of EAD and biliary complications were significantly reduced with an odds ratio (OR) of 0.36 (95% confidence interval [CI] 0.17–0.77, P = .008) and 0.47 (95% CI 0.28–0.76, P = .003), respectively, and 1-year graft survival was significantly increased with an OR of 2.19 (95% CI 1.14–4.20, P = .02) in HMP preservation compared to SCS. However, there was no difference in the incidence of PNF (OR 0.30, 95% CI 0.06–1.47, P = .14), vascular complications (OR 0.69, 95% CI 0.29–1.66, P = .41), and the length of hospital stay (mean difference −0.30, 95% CI −4.10 to 3.50, P = .88) between HMP and SCS preservation.

          Conclusions:

          HMP was associated with a reduced incidence of EAD and biliary complications, as well as an increased 1-year graft survival, but it was not associated with the incidence of PNF, vascular complications, and the length of hospital stay.

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          Most cited references31

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          Machine perfusion or cold storage in deceased-donor kidney transplantation.

          Cyril Moers, Jacqueline Smits, Mark-Hugo J Maathuis … (2009)
          Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.) 2009 Massachusetts Medical Society
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            Hypothermic machine preservation in human liver transplantation: the first clinical series.

            J Guarrera, S D Henry, B Samstein … (2010)
            Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.
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              First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis.

              Philipp Dutkowski, Wojciech Polak, Paolo Muiesan … (2015)
              Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: June 2019
                Publication date (Electronic): 07 June 2019
                Volume: 98
                Issue: 23
                Electronic Location Identifier: e16033
                Affiliations
                [a ]Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University
                [b ]Department of Blood Transfusion, Xi’an Central Hospital
                [c ]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China.
                Author notes
                [∗ ]Correspondence: Shengli Wu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, Yanta West Road, Xi’an, Shaanxi 710061, China (e-mail: victorywu2000@ 123456163.com ).
                Article
                Publisher ID: MD-D-19-01311 Accession ID: 16033
                DOI: 10.1097/MD.0000000000016033
                PMC ID: 6571373
                PubMed ID: 31169745
                SO-VID: 821c575f-16f8-4912-832f-539b2dcc89b0
                Copyright © Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                Date received : 16 February 2019
                Date revision received : 20 May 2019
                Date accepted : 22 May 2019
                Categories
                Subject: 4500
                Subject: Research Article
                Subject: Systematic Review and Meta-Analysis
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: hypothermic machine perfusion,liver,meta-analysis,static cold storage,transplant
                Data availability:
                Keywords: hypothermic machine perfusion, liver, meta-analysis, static cold storage, transplant

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