Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: A European observational cohort study
2022; Elsevier BV; Volume: 22; Issue: 7 Linguagem: Inglês
10.1111/ajt.17037
ISSN1600-6143
AutoresIsabel M.A. Brüggenwirth, Matteo Mueller, Veerle A. Lantinga, Stefania Camagni, Riccardo De Carlis, Luciano De Carlis, M. Colledan, Daniele Dondossola, Moritz Drefs, Janina Eden, Davide Ghinolfi, Dionysios Koliogiannis, Georg Lurje, Tommaso Maria Manzia, Diethard Monbaliu, Paolo Muiesan, Damiano Patrono, Johann Pratschke, Renato Romagnoli, Michel Rayar, F. Roma, Andrea Schlegel, Philipp Dutkowski, Robert J. Porte, Vincent E. de Meijer,
Tópico(s)Transplantation: Methods and Outcomes
ResumoAmerican Journal of TransplantationVolume 22, Issue 7 p. 1842-1851 ORIGINAL ARTICLEOpen Access Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: A European observational cohort study Isabel M. A. Brüggenwirth, Isabel M. A. Brüggenwirth orcid.org/0000-0002-8557-7081 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorMatteo Mueller, Matteo Mueller orcid.org/0000-0002-1118-156X Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorVeerle A. Lantinga, Veerle A. Lantinga orcid.org/0000-0002-6931-2825 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorStefania Camagni, Stefania Camagni orcid.org/0000-0002-3037-7904 Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Bergamo, ItalySearch for more papers by this authorRiccardo De Carlis, Riccardo De Carlis orcid.org/0000-0003-3697-1653 Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, ItalySearch for more papers by this authorLuciano De Carlis, Luciano De Carlis orcid.org/0000-0002-9133-8220 Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy School of Medicine and Surgery, University of Milano-Bicocca, Milan, ItalySearch for more papers by this authorMichele Colledan, Michele Colledan orcid.org/0000-0002-3880-4763 Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy School of Medicine and Surgery, University of Milano-Bicocca, Milan, ItalySearch for more papers by this authorDaniele Dondossola, Daniele Dondossola orcid.org/0000-0002-4374-3184 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorMoritz Drefs, Moritz Drefs orcid.org/0000-0002-0662-7643 Department of General, Visceral, and Transplant Surgery, University Hospital of Munich, Munich, GermanySearch for more papers by this authorJanina Eden, Janina Eden orcid.org/0000-0002-8724-9313 Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorDavide Ghinolfi, Davide Ghinolfi orcid.org/0000-0001-7933-8941 Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, ItalySearch for more papers by this authorDionysios Koliogiannis, Dionysios Koliogiannis orcid.org/0000-0002-8001-8547 Department of General, Visceral, and Transplant Surgery, University Hospital of Munich, Munich, GermanySearch for more papers by this authorGeorg Lurje, Georg Lurje orcid.org/0000-0001-9674-0756 Department of Surgery, Charité—Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorTommaso M. Manzia, Tommaso M. Manzia orcid.org/0000-0002-4636-3478 Hepato-Pancreato-Biliary and Transplant Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorDiethard Monbaliu, Diethard Monbaliu orcid.org/0000-0002-0506-1609 Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Catholic University Leuven, Leuven, BelgiumSearch for more papers by this authorPaolo Muiesan, Paolo Muiesan orcid.org/0000-0002-7389-6691 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorDamiano Patrono, Damiano Patrono orcid.org/0000-0002-4096-4504 AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, ItalySearch for more papers by this authorJohann Pratschke, Johann Pratschke orcid.org/0000-0001-9839-1369 Department of Surgery, Charité—Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorRenato Romagnoli, Renato Romagnoli orcid.org/0000-0001-8340-8885 AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, ItalySearch for more papers by this authorMichel Rayar, Michel Rayar orcid.org/0000-0003-3113-2260 CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, FranceSearch for more papers by this authorFederico Roma, Federico Roma orcid.org/0000-0002-6370-5708 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorAndrea Schlegel, Andrea Schlegel orcid.org/0000-0002-9385-9847 Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorPhilipp Dutkowski, Philipp Dutkowski orcid.org/0000-0002-3016-604X Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorRobert J. Porte, Robert J. Porte orcid.org/0000-0003-0538-734X Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorVincent E. de Meijer, Corresponding Author Vincent E. de Meijer v.e.de.meijer@umcg.nl orcid.org/0000-0002-7900-5917 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands Correspondence Vincent E. de Meijer, Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. Email: v.e.de.meijer@umcg.nlSearch for more papers by this author Isabel M. A. Brüggenwirth, Isabel M. A. Brüggenwirth orcid.org/0000-0002-8557-7081 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorMatteo Mueller, Matteo Mueller orcid.org/0000-0002-1118-156X Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorVeerle A. Lantinga, Veerle A. Lantinga orcid.org/0000-0002-6931-2825 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorStefania Camagni, Stefania Camagni orcid.org/0000-0002-3037-7904 Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Bergamo, ItalySearch for more papers by this authorRiccardo De Carlis, Riccardo De Carlis orcid.org/0000-0003-3697-1653 Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, ItalySearch for more papers by this authorLuciano De Carlis, Luciano De Carlis orcid.org/0000-0002-9133-8220 Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy School of Medicine and Surgery, University of Milano-Bicocca, Milan, ItalySearch for more papers by this authorMichele Colledan, Michele Colledan orcid.org/0000-0002-3880-4763 Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy School of Medicine and Surgery, University of Milano-Bicocca, Milan, ItalySearch for more papers by this authorDaniele Dondossola, Daniele Dondossola orcid.org/0000-0002-4374-3184 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorMoritz Drefs, Moritz Drefs orcid.org/0000-0002-0662-7643 Department of General, Visceral, and Transplant Surgery, University Hospital of Munich, Munich, GermanySearch for more papers by this authorJanina Eden, Janina Eden orcid.org/0000-0002-8724-9313 Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorDavide Ghinolfi, Davide Ghinolfi orcid.org/0000-0001-7933-8941 Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, ItalySearch for more papers by this authorDionysios Koliogiannis, Dionysios Koliogiannis orcid.org/0000-0002-8001-8547 Department of General, Visceral, and Transplant Surgery, University Hospital of Munich, Munich, GermanySearch for more papers by this authorGeorg Lurje, Georg Lurje orcid.org/0000-0001-9674-0756 Department of Surgery, Charité—Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorTommaso M. Manzia, Tommaso M. Manzia orcid.org/0000-0002-4636-3478 Hepato-Pancreato-Biliary and Transplant Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorDiethard Monbaliu, Diethard Monbaliu orcid.org/0000-0002-0506-1609 Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Catholic University Leuven, Leuven, BelgiumSearch for more papers by this authorPaolo Muiesan, Paolo Muiesan orcid.org/0000-0002-7389-6691 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorDamiano Patrono, Damiano Patrono orcid.org/0000-0002-4096-4504 AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, ItalySearch for more papers by this authorJohann Pratschke, Johann Pratschke orcid.org/0000-0001-9839-1369 Department of Surgery, Charité—Universitätsmedizin Berlin, Berlin, GermanySearch for more papers by this authorRenato Romagnoli, Renato Romagnoli orcid.org/0000-0001-8340-8885 AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, ItalySearch for more papers by this authorMichel Rayar, Michel Rayar orcid.org/0000-0003-3113-2260 CHU Rennes, Service de Chirurgie Hépatobiliaire et Digestive, Rennes, FranceSearch for more papers by this authorFederico Roma, Federico Roma orcid.org/0000-0002-6370-5708 General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorAndrea Schlegel, Andrea Schlegel orcid.org/0000-0002-9385-9847 Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan and Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalySearch for more papers by this authorPhilipp Dutkowski, Philipp Dutkowski orcid.org/0000-0002-3016-604X Department of Surgery and Transplantation, University Hospital Zurich, Zurich, SwitzerlandSearch for more papers by this authorRobert J. Porte, Robert J. Porte orcid.org/0000-0003-0538-734X Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The NetherlandsSearch for more papers by this authorVincent E. de Meijer, Corresponding Author Vincent E. de Meijer v.e.de.meijer@umcg.nl orcid.org/0000-0002-7900-5917 Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands Correspondence Vincent E. de Meijer, Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. Email: v.e.de.meijer@umcg.nlSearch for more papers by this author First published: 21 March 2022 https://doi.org/10.1111/ajt.17037Citations: 2 Robert J. Porte and Vincent E. de Meijer share last authorship. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract A short period (1–2 h) of hypothermic oxygenated machine perfusion (HOPE) after static cold storage is safe and reduces ischemia-reperfusion injury-related complications after liver transplantation. Machine perfusion time is occasionally prolonged for logistical reasons, but it is unknown if prolonged HOPE is safe and compromises outcomes. We conducted a multicenter, observational cohort study of patients transplanted with a liver preserved by prolonged (≥4 h) HOPE. Postoperative biochemistry, complications, and survival were evaluated. The cohort included 93 recipients from 12 European transplant centers between 2014–2021. The most common reason to prolong HOPE was the lack of an available operating room to start the transplant procedure. Grafts underwent HOPE for a median (range) of 4:42 h (4:00–8:35 h) with a total preservation time of 10:50 h (5:50–20:50 h). Postoperative peak ALT was 675 IU/L (interquartile range 419–1378 IU/L). The incidence of postoperative complications was low, and 1-year graft and patient survival were 94% and 88%, respectively. To conclude, good outcomes are achieved after transplantation of donor livers preserved with prolonged (median 4:42 h) HOPE, leading to a total preservation time of almost 21 h. These results suggest that simple, end-ischemic HOPE may be utilized for safe extension of the preservation time to ease transplantation logistics. Abbreviations AKI acute kidney injury ALT alanine aminotransferase AST aspartate aminotransferase BAR balance of risks BMI body mass index CVVH continuous veno-venous hemofiltration DBD donation after brain death DCD donation after circulatory death DHOPE dual hypothermic oxygenated machine perfusion EAD early allograft dysfunction HAT hepatic artery thrombosis HCC hepatocellular carcinoma HOPE hypothermic oxygenated machine perfusion INR international normalized ratio IQR interquartile range MELD model for end-stage liver disease mpEAD machine perfusion early allograft dysfunction NAS nonanastomotic biliary strictures NMP normothermic machine perfusion PNF primary nonfunction PRS post-reperfusion syndrome PVT portal vein thrombosis SCS static cold storage yGT gamma-glutamyl transferase 1 INTRODUCTION The use of machine perfusion to preserve donor livers is one of the most important advances in liver transplantation in the past decade. Hypothermic oxygenated machine perfusion (HOPE) is performed at 4–12°C with an acellular perfusion solution at low perfusion pressures and flow rates.1 Hypothermic oxygenation of mitochondria induces metabolic programming within 1 h, thereby decreasing mitochondrial succinate accumulation and uploading adenosine triphosphate levels.2 Reperfusion of livers treated by end-ischemic HOPE is, therefore, associated with less oxidative injury and mitochondrial damage with subsequently less downstream inflammation.2-4 The results of two recently published randomized controlled trials comparing end-ischemic HOPE versus static cold storage (SCS) confirm the beneficial effects of this technique on clinical outcomes.5, 6 In the transplantation of donation after circulatory death (DCD) livers, 2 h of HOPE after SCS reduced the incidence of ischemia-reperfusion-related complications after transplantation, including a 68% reduction in symptomatic nonanastomotic biliary strictures (NAS), when compared to grafts preserved with SCS alone.5 In the transplantation of livers from high-risk donation after brain death (DBD) donors, approximately 2 h of end-ischemic HOPE reduced the incidence of early allograft dysfunction (EAD) and postoperative complications.6 Whereas a brief period (usually 1–2 h) of HOPE after SCS improves post-transplant outcomes, machine perfusion time may occasionally be prolonged because of unforeseen transplant logistics. For example, when the donor liver is reallocated to another recipient in the last minute, or in the event of a difficult recipient hepatectomy.7-9 Good outcomes after prolonged normothermic machine perfusion (NMP) up to 20 h have been reported previously,10 but the use of prolonged HOPE is still unexplored. In a preclinical study of porcine and discarded human livers, HOPE could succesfully be prolonged for up to 24 h, followed by normothermic reperfusion.11 However, clinical data are currently lacking and it remains unknown whether postoperative outcomes are compromised when HOPE is prolonged beyond 2 h. The objective of this multicenter study was, therefore, to evaluate outcomes after transplantation of donor livers preserved by prolonged (≥4 h) HOPE. We hypothesize that good outcomes after prolonged HOPE can be achieved, which are comparable to those previously reported for regular HOPE. 2 METHODS 2.1 Study design European liver transplant centers with a clinical HOPE program were approached for participation in this multicenter observational cohort study. All cases of prolonged (≥4 h) HOPE-preserved donor livers and recipients were eligible for inclusion in the study. There were no exclusion criteria. The study was designed as a stage 1 study according to the IDEAL-D (Idea, Exploration, Assessment, Long-term study outcomes for Devices) framework.12-14 IDEAL stage 1 (‘Idea’) studies describe the first use of a procedure or device, either as a planned or unplanned approach with short-term clinical outcomes as endpoints. The study was approved by the Institutional Review Board of the University Medical Center Groningen (RR 202100366) and adhered to the Declaration of Helsinki and the Declaration of Istanbul. The first and last authors had full access to all data in the study and take responsibility for its integrity and the data analysis. The study complied with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.15 2.2 Liver procurement, preservation, and transplantation Donor livers were obtained, preserved, and transported to recipient transplant centers according to standard national practice. The transplantation surgery and postoperative care were performed according to standard local practice. According to national legislation, livers from DCD donors in Italy were retrieved with in situ normothermic regional perfusion. The Liver Assist device (XVIVO), VitaSmart (Medica), or a custom-made device by the Bergamo group was used for end-ischemic HOPE of the liver. The devices enable pressure-controlled, single or dual perfusion using a centrifugal pump or roller pump to provide a continuous flow through the portal vein and, in case of dual perfusion, a pulsatile flow through the hepatic artery. The Bergamo devices was based on a heart-lung machine combined with an oxygenator with heat-exchange performance (Quadrox-i) and a cardiotomy reservoir (VHK). The perfusion systems were filled with an acellular preservation solution. The perfusion pressure was set to 20–30 mmHg in the hepatic artery and 3–9 mmHg in the portal vein. The temperature of the perfusion fluid was maintained between 8–12°C. Oxygenation of the perfusion solution was provided by membrane oxygenators supplying 100% oxygen to the preservation solution to target partial oxygen pressures of at least 70 kPa. Livers included in this study were perfused for at least 4 h. 2.3 Survey An online questionnaire was sent to the program leader from each participating center. The survey included 10 questions about the centers’ experience with HOPE and the surgeon's view on prolonged HOPE. 2.4 Data collection Data were collected at each center and anonymously stored in a single electronic database. Donor and recipient characteristics included age, the body mass index (BMI), the model for end-stage liver disease (MELD) score, the donor risk index (DRI), the Eurotransplant DRI (ET-DRI), and the balance of risks (BAR) score. The DRI is calculated based on the following donor characteristics: age, race, height, cause of death, DCD, and whether it was a partial or split graft.16 By adding the latest laboratory gamma-glutamyl transferase (yGT) of the donor and rescue allocation, the ET-DRI was developed.17 The BAR score is calculated based on the following variables: MELD score, retransplantation, whether the recipient was on life support preoperatively, recipient age, cold ischemia time, and donor age.18 Postoperative outcomes included the occurrence of post-reperfusion syndrome (PRS) (as defined below), postoperative laboratory values up to day 7 (lactate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], yGT, bilirubin, creatinine, and international normalized ratio [INR]), intensive-care and total hospital length of stay, primary non-function (PNF), EAD, portal vein or hepatic artery thrombosis, NAS, acute kidney injury (AKI), complications according to Clavien-Dindo grading, and 1-year graft and patient survival. 2.5 Definitions Post-reperfusion syndrome was defined as (1) a decrease in mean arterial blood pressure ≥30 mmHg below baseline, lasting for ≥1 min, within 5 min after reperfusion (Aggarwal criteria19), or (2) a fall in mean arterial blood pressure on reperfusion 2 U/h vasopressin, or infusion of epinephrine (Watson crtiteria20). Primary nonfunction was defined as nonlife sustaining graft function leading to graft loss or retransplantation within the first week after liver transplantation. Both the definition of EAD according to Olthoff et al.21 as well as a modified machine perfusion EAD (mpEAD) were used. Since the definition of EAD according to Olthoff et al. was coined prior to the introduction of machine perfusion, it does not take into account the so-called washout effect of liver transaminases during/after machine perfusion (ILTS guidelines 202122). Hence, transaminases are likely to be lower in recipients transplanted by a machine-perfused graft. The mpEAD was defined as the presence of 1 or more of the following on postoperative day 7: bilirubin ≥10 mg/dl, INR ≥1.6, or lactate ≥2 mmol/L in the absence of vascular complications. Vascular thrombosis was defined as a radiologically or surgically proven thrombus of the portal vein or hepatic artery. NAS were defined as any nonanastomotic biliary complication leading to surgical or endoscopic intervention within 12 months after liver transplantation, in the absence of concomitant hepatic artery thrombosis, or anastomotic stenosis.23 Biliary leakage was defined as fluid with an elevated bilirubin level in the abdominal drain or intra-abdominal fluid on or after postoperative day three or the need for radiological intervention owing to biliary collections or relaparotomy due to biliary peritonitis.24 Acute kidney injury was defined as (1) increase serum creatinine by ≥0.3 mg/dl within 48 h after transplantation or, (2) increase in serum creatinine ≥1.5 times baseline, or (3) urine volume <0.5 ml/kg/h for 6 h.25 Graft survival was defined as the time between liver transplantation and retransplantation or death. Graft survival was censored for patients dying with a functional graft. Patient survival was defined as the time between liver transplantation and all-cause death. 2.6 Statistical analysis Continuous variables are expressed as median and interquartile range, unless stated otherwise. Categorical variables are expressed as frequencies and proportions (%). Kaplan–Meier survival curves were used to graphically depict patient and graft survival. In one subanalysis, outcomes after prolonged HOPE were compared between DBD and DCD livers. Another subanalysis compared outcomes after prolonged single HOPE versus dual HOPE. Categorical variables were compared using Chi-square test and continuous variables with a Mann–Whitney U test. p-values < .05 were considered statistically significant. Data were analyzed with IBM SPSS Statistics version 24 (IBM Corporation) and Prism 8. 3 RESULTS 3.1 Study population A total of 93 patients were transplanted with a donor liver after prolonged HOPE. In this cohort, the median donor age was 57 (50–68) years and 46% of livers were from DCD donors (Table 1). In case of DCD liver donation, median functional warm ischemia time was 32 (26–52) minutes. The median DRI and ET-DRI scores were 2.24 (1.88–2.45) and 1.96 (1.81–2.30), respectively. The median recipient age was 59 (53–65) years and the majority was male (78%). Prior to liver transplantation, the median BAR score was 5 (3–8). The most common indications for liver transplantation were alcoholic cirrhosis (22%), hepatocellular carcinoma (17%), and nonalcoholic steatohepatitis (16%). TABLE 1. Baseline characteristics Characteristics Patients (n = 93)n (%) or median(IQR) Donor Age—year 57 (50–68) Male sex—no. (%) 60 (65%) Body mass index—kg/m2 25 (23–28) Type of donor—no. (%) DBD 50 (54%) DCD 43 (46%) Donor Risk Indexa a The donor risk index includes seven donor and graft characteristics that are significantly and independently associated with increased failure of deceased donor liver transplants.16 2.24 (1.88–2.45) Eurotransplant Donor Risk Indexb b The Eurotransplant donor risk index was based on the donor risk index by adding the latest laboratory yGT of the donor and rescue allocation.17 1.96 (1.81–2.30) Recipient Age—year 59 (53–65) Male sex—no. (%) 73 (78%) Body-mass index—kg/m2 27 (23–29) Laboratory MELD scorec c The laboratory MELD score ranges from 6 to 40 with higher scores indicating more advanced disease. 12 (9–19) Balance of risk scored d The balance of risk score is a scoring system that was developed to detect unfavorable combinations of donor and recipient factors on the risk of graft failure after liver transplantation.18 5 (3–8) Indication for transplantation—no. (%) Alcoholic cirrhosis 20 (22%) HCC 16 (17%) NASH 15 (16%) HCV 14 (15%) HBV 6 (6.5%) Cholangiopathy 7 (7.5%) Retransplantation 3 (3.2%) AIH 2 (2.2%) Other 10 (11%) Child Pugh Score—no. (%) A 36 (39%) B 33 (35%) C 21 (23%) Missing 3 (3.2%) Machine perfusion Type of machine perfusion—no. (%) HOPE 38 (41%) DHOPE 55 (59%) Indication for prolonged HOPE—no. (%) Operating room logistics 34 (37%) Difficult recipient hepatectomy 27 (29%) Uncontrolled DCD in Italy 18 (19%) Change of recipient 10 (11%) Split liver on the pump 4 (4.3%) Portal venous pressure—mmHg 4 (3–5) Hepatic artery pressure—mmHg 25 (24–25) Portal venous flow start—ml/min 230 (140–310) Portal venous flow end—ml/min 251 (150–486) Hepatic artery flow start—ml/min 49 (38–82) Hepatic artery flow end—ml/min 75 (66–115) Temperature—°C 9 (7–10) Oxygenation—kPa 97 (81–106) Abbreviations: AIH, autoimmune hepatitis; DBD, donation after brain death; DCD, donation after circulatory death; HBV, viral hepatitis B; HCC, hepatocellular carcinoma; HCV, viral hepatitis C; MELD, model for end-stage liver disease; NASH, nonalcoholic steatohepatitis. a The donor risk index includes seven donor and graft characteristics that are significantly and independently associated with increased failure of deceased donor liver transplants.16 b The Eurotransplant donor risk index was based on the donor risk index by adding the latest laboratory yGT of the donor and rescue allocation.17 c The laboratory MELD score ranges from 6 to 40 with higher scores indicating more advanced disease. d The balance of risk score is a scoring system that was developed to detect unfavorable combinations of donor and recipient factors on the risk of graft failure after liver transplantation.18 3.2 Survey outcomes and center characteristics Twelve transplant centers in 6 European countries (the Netherlands, Germany, Belgium, Italy, Switzerland, and France) contributed to the study. The median number of liver transplantations performed per year in the participating centers was 80 (60–130) (Table S1). In 5
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