Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD)
Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu klinické zkoušky, fáze II, časopisecké články, multicentrická studie, randomizované kontrolované studie
PubMed
29018070
PubMed Central
PMC5652559
DOI
10.1136/bmjopen-2017-017558
PII: bmjopen-2017-017558
Knihovny.cz E-zdroje
- Klíčová slova
- donation after brain death, extended criteria donor, hypothermic oxygenated machine perfusion,
- MeSH
- alografty * MeSH
- dárci tkání * MeSH
- dospělí MeSH
- játra * patologie chirurgie MeSH
- konečné stadium selhání jater chirurgie MeSH
- kyslík * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková smrt * MeSH
- perfuze MeSH
- přežívání štěpu * MeSH
- prospektivní studie MeSH
- senioři MeSH
- transplantace jater * MeSH
- získávání tkání a orgánů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- kyslík * MeSH
INTRODUCTION: Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT. METHODS AND ANALYSIS: HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018. TRIAL REGISTRATION NUMBER: NCT03124641.
Department of Anesthesiology University Hospital RWTH Aachen Aachen Germany
Department of General Surgery and Liver transplantation Fundeni Clinical Institute Bucharest Romania
Department of Medicine 3 University Hospital RWTH Aachen Aachen Germany
Department of Solid Organ Transplantation Ghent University Hospital and Medical School Ghent Belgium
Department of Surgery and Transplantation University Hospital RWTH Aachen Aachen Germany
Department of Surgery Maastricht University Medical Centre Maastricht Netherlands
Zobrazit více v PubMed
Starzl TE, Fung JJ. Themes of liver transplantation. Hepatology 2010;51:1869–84. 10.1002/hep.23595 PubMed DOI PMC
Tacke F, Kroy DC, Barreiros AP, et al. . Liver transplantation in Germany. Liver Transpl 2016;22:1136–42. 10.1002/lt.24461 PubMed DOI
Schlegel A, Kron P, Dutkowski P. Hypothermic machine perfusion in liver transplantation. Curr Opin Organ Transplant 2016;21:308–14. 10.1097/MOT.0000000000000303 PubMed DOI
Marecki H, Bozorgzadeh A, Porte RJ, et al. . Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials. Liver Transpl 2017;23:679–95. 10.1002/lt.24751 PubMed DOI
Gurusamy KS, Gonzalez HD, Davidson BR. Current protective strategies in liver surgery. World J Gastroenterol 2010;16:6098–103. 10.3748/wjg.v16.i48.6098 PubMed DOI PMC
Compagnon P, Levesque E, Hentati H, et al. . An oxygenated and transportable machine perfusion system fully rescues liver grafts exposed to lethal ischemic damage in a pig model of DCD liver transplantation. Transplantation 2017;101:e205–e213. 10.1097/TP.0000000000001764 PubMed DOI
Ceresa CDL, Nasralla D, Knight S, et al. . Cold storage or normothermic perfusion for liver transplantation: probable application and indications. Curr Opin Organ Transplant 2017;22:300–5. 10.1097/MOT.0000000000000410 PubMed DOI
Dutkowski P, Polak WG, Muiesan P, et al. . First comparison of hypothermic oxygenated perfusion versus static cold storage of human donation after cardiac death liver transplants: an international-matched case analysis. Ann Surg 2015;262:764–71. discussion 770-1 10.1097/SLA.0000000000001473 PubMed DOI
Lurje G, Raptis DA, Steinemann DC, et al. . Cosmesis and body image in patients undergoing single-port versus conventional laparoscopic cholecystectomy: a multicenter double-blinded randomized controlled trial (SPOCC-trial). Ann Surg 2015;262:728–34. discussion 734-5 10.1097/SLA.0000000000001474 PubMed DOI
Steinemann DC, Raptis DA, Lurje G, et al. . Cosmesis and body image after single-port laparoscopic or conventional laparoscopic cholecystectomy: a multicenter double blinded randomised controlled trial (SPOCC-trial). BMC Surg 2011;11:24 10.1186/1471-2482-11-24 PubMed DOI PMC
Kleiner DE, Brunt EM, Van Natta M, et al. . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–21. 10.1002/hep.20701 PubMed DOI
Westerkamp AC, de Boer MT, van den Berg AP, et al. . Similar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short. Transpl Int 2015;28:319–29. 10.1111/tri.12504 PubMed DOI
Chu MJ, Dare AJ, Phillips AR, et al. . Donor hepatic steatosis and outcome after liver transplantation: a systematic review. J Gastrointest Surg 2015;19:1713–24. 10.1007/s11605-015-2832-1 PubMed DOI
McCormack L, Dutkowski P, El-Badry AM, et al. . Liver transplantation using fatty livers: always feasible? J Hepatol 2011;54:1055–62. 10.1016/j.jhep.2010.11.004 PubMed DOI
RichtlinienfürdieWartelistenführungundOrganvermittlungzurLebertransplantationgem. § 16 Abs. 1 S. 1 Nrn. 2 u. 5 TPG. Bundesärztekamme:29.
Mossdorf A, Ulmer F, Junge K, et al. . Bypass during liver transplantation: anachronism or revival? liver transplantation using a combined venovenous/portal venous bypass—experiences with 163 liver transplants in a newly established liver transplantation program. Gastroenterol Res Pract 2015;2015:1–7. 10.1155/2015/967951 PubMed DOI PMC
Kienlein S, Schoening W, Andert A, et al. . Biliary complications in liver transplantation: Impact of anastomotic technique and ischemic time on short- and long-term outcome. World J Transplant 2015;5:300–9. 10.5500/wjt.v5.i4.300 PubMed DOI PMC
Neuhaus P, Blumhardt G, Bechstein WO, et al. . Technique and results of biliary reconstruction using side-to-side choledochocholedochostomy in 300 orthotopic liver transplants. Ann Surg 1994;219:426–34. 10.1097/00000658-199404000-00014 PubMed DOI PMC
Op den Dries S, Sutton ME, Karimian N, et al. . Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PLoS One 2014;9:e88521 10.1371/journal.pone.0088521 PubMed DOI PMC
Slankamenac K, Graf R, Barkun J, et al. . The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg 2013;258:1–7. 10.1097/SLA.0b013e318296c732 PubMed DOI
Olthoff KM, Kulik L, Samstein B, et al. . Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010;16:943–9. 10.1002/lt.22091 PubMed DOI
Guarrera JV, Henry SD, Samstein B, et al. . Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant 2010;10:372–81. 10.1111/j.1600-6143.2009.02932.x PubMed DOI
Dutkowski P, Schlegel A, de Oliveira M, et al. . HOPE for human liver grafts obtained from donors after cardiac death. J Hepatol 2014;60:765–72. 10.1016/j.jhep.2013.11.023 PubMed DOI
Schlegel A, Dutkowski P. Role of hypothermic machine perfusion in liver transplantation. Transpl Int 2015;28:677–89. 10.1111/tri.12354 PubMed DOI
Schlegel A, Kron P, Dutkowski P. Hypothermic oxygenated liver perfusion: basic mechanisms and clinical application. Curr Transplant Rep 2015;2:52–62. 10.1007/s40472-014-0046-1 PubMed DOI PMC
Schlegel A, Kron P, Graf R, et al. . Hypothermic oxygenated perfusion (HOPE) downregulates the immune response in a rat model of liver transplantation. Ann Surg 2014;260:931–8. discussion 937-8 10.1097/SLA.0000000000000941 PubMed DOI
Yang Z, Zhong Z, Li M, et al. . Hypothermic machine perfusion increases A20 expression which protects renal cells against ischemia/reperfusion injury by suppressing inflammation, apoptosis and necroptosis. Int J Mol Med 2016;38:161–71. 10.3892/ijmm.2016.2586 PubMed DOI PMC
Fu Z, Ye Q, Zhang Y, et al. . Hypothermic machine perfusion reduced inflammatory reaction by downregulating the expression of matrix metalloproteinase 9 in a reperfusion model of donation after cardiac death. Artif Organs 2016;40:E102–E111. 10.1111/aor.12658 PubMed DOI
Mazzolini G, Sowa JP, Canbay A. Cell death mechanisms in human chronic liver diseases: a far cry from clinical applicability. Clin Sci 2016;130:2121–38. 10.1042/CS20160035 PubMed DOI
Westerkamp AC, Karimian N, Matton AP, et al. . Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers. Transplantation 2016;100:825–35. 10.1097/TP.0000000000001081 PubMed DOI
Westerkamp AC, Mahboub P, Meyer SL, et al. . End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature. Liver Transpl 2015;21:1300–11. 10.1002/lt.24200 PubMed DOI
Jia JJ, Zhang J, Li JH, et al. . Influence of perfusate on liver viability during hypothermic machine perfusion. World J Gastroenterol 2015;21:8848–57. 10.3748/wjg.v21.i29.8848 PubMed DOI PMC
Monbaliu D, Liu Q, Libbrecht L, et al. . Preserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: a proof-of-concept study using discarded human livers. Liver Transpl 2012;18:1495–507. 10.1002/lt.23550 PubMed DOI
de Rougemont O, Dutkowski P, Clavien PA. Biological modulation of liver ischemia-reperfusion injury. Curr Opin Organ Transplant 2010;15:183–9. 10.1097/MOT.0b013e3283373ced PubMed DOI
Guan LY, Fu PY, Li PD, et al. . Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide. World J Gastrointest Surg 2014;6:122–8. 10.4240/wjgs.v6.i7.122 PubMed DOI PMC
van Rijn R, Karimian N, Matton APM, et al. . Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death. Br J Surg 2017;104:907–17. 10.1002/bjs.10515 PubMed DOI PMC
Schlegel A, Graf R, Clavien PA, et al. . Hypothermic oxygenated perfusion (HOPE) protects from biliary injury in a rodent model of DCD liver transplantation. J Hepatol 2013;59:984–91. 10.1016/j.jhep.2013.06.022 PubMed DOI
Schlegel A, Kron P, De Oliveira ML, et al. . Is single portal vein approach sufficient for hypothermic machine perfusion of DCD liver grafts? J Hepatol 2016;64:239–41. 10.1016/j.jhep.2015.09.015 PubMed DOI
Brüggenwirth IMA, Burlage LC, Porte RJ, et al. . Is single portal vein perfusion the best approach for machine preservation of liver grafts? J Hepatol 2016;64:1194–5. 10.1016/j.jhep.2015.12.025 PubMed DOI
Schlegel A, Kron P, de Oliveira ML, et al. . Reply to ’Is single portal vein perfusion the best approach for machine preservation of liver grafts?'. J Hepatol 2016;64:1195–6. 10.1016/j.jhep.2016.01.033 PubMed DOI
ClinicalTrials.gov
NCT03124641
