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Blondeel J, van Leeuwen OB, Schurink IJ, Lantinga VA, Gilbo N, de Goeij FHC, Pirenne J, Huurman VAL, de Meijer VE, de Jonge J, Porte RJ, Monbaliu D. Dynamic Preservation of Donation After Circulatory Death Liver Grafts From Donors Aged 60 y and Older. Transplantation 2025; 109:844-852. [PMID: 39702514 DOI: 10.1097/tp.0000000000005297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
BACKGROUND Donor livers from older donation after circulatory death (DCD) donors are frequently discarded for transplantation because of the high risk of graft failure. It is unknown whether DCD livers from older donors benefit from dynamic preservation. METHODS In a multicenter study, we retrospectively compared graft and patient outcomes after transplantation of livers from DCD donors older than 60 y, preserved with either static cold storage (SCS), ex situ sequential dual hypothermic perfusion, controlled oxygenated rewarming, and normothermic perfusion (DHOPE-COR-NMP), or in situ abdominal normothermic regional perfusion (aNRP). RESULTS Fifty-six liver transplants were included in the SCS cohort, 33 in the DHOPE-COR-NMP cohort, and 27 in the aNRP cohort. Donor warm ischemia time was significantly shorter in the SCS group than in DHOPE-COR-NMP ( P < 0.001) and aNRP ( P < 0.001) groups. Cold ischemia times were similar. One-year incidence of nonanastomotic biliary strictures was lower after DHOPE-COR-NMP (3%, P = 0.03) or aNRP (7%, P = 0.13), compared with SCS alone (21%). Anastomotic strictures were less frequent in aNRP (19%) compared with DHOPE-COR-NMP (52%; P = 0.015). One-year graft and patient survival were similar. CONCLUSIONS Dynamic preservation allows safe transplantation of livers from DCD donors aged 60 y or older. The risk of nonanastomotic strictures was significantly lower after DHOPE-COR-NMP than after SCS, despite longer donor warm ischemia times.
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Affiliation(s)
- Joris Blondeel
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Otto B van Leeuwen
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ivo J Schurink
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Veerle A Lantinga
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Nicholas Gilbo
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Surgery and Transplantation, CHU Liege, Liege, Belgium
| | - Femke H C de Goeij
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Jacques Pirenne
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Volkert A L Huurman
- Department of Surgery, Leiden University Medical Center Transplant Center, Leiden University Medical Center, Leiden, the Netherlands
| | - Vincent E de Meijer
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jeroen de Jonge
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Robert J Porte
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Diethard Monbaliu
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
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Jeddou H, Tzedakis S, Chaouch MA, Sulpice L, Samson M, Boudjema K. Viability Assessment During Normothermic Machine Liver Perfusion: A Literature Review. Liver Int 2025; 45:e16244. [PMID: 39821671 PMCID: PMC11740183 DOI: 10.1111/liv.16244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 12/25/2024] [Accepted: 01/03/2025] [Indexed: 01/19/2025]
Abstract
BACKGROUND AND OBJECTIVE The discrepancy between donor organ availability and demand leads to a significant waiting-list dropout rate and mortality. Although quantitative tools such as the Donor Risk Index (DRI) help assess organ suitability, many potentially viable organs are still discarded due to the lack of universally accepted markers to predict post-transplant outcomes. Normothermic machine perfusion (NMP) offers a platform to assess viability before transplantation. Thus, livers considered unsuitable for transplantation based on the DRI can be evaluated and potentially transplanted. During NMP, various viability criteria have been proposed. These criteria are neither homogeneous nor consensual. In this review, we aimed to describe the viability criteria during NMP and evaluate their ability to predict hepatic graft function following transplantation. We conducted a PubMed search using the terms 'liver transplantation', 'normothermic machine perfusion' and 'assessment', including only English publications up to February 2024. Viability assessment during NMP includes multiple hepatocellular and cholangiocellular criteria. Lactate clearance and bile production are commonly used indicators, but their ability to predict post-transplant outcomes varies significantly. The predictive value of cholangiocellular criteria such as bile pH, bicarbonate and glucose levels remains under investigation. Novel markers, such as microRNAs and proteomic profiles, offer the potential to enhance graft evaluation accuracy and provide insights into the molecular mechanisms underlying liver viability. Combining perfusion parameters with biomarkers may improve the prediction of long-term graft survival. Future research should focus on standardising viability assessment protocols and exploring real-time biomarker evaluations, which could enhance transplantation outcomes and expand the donor pool.
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Affiliation(s)
- Heithem Jeddou
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
| | - Stylianos Tzedakis
- Department of Hepato‐Biliary, Digestive and Endocrine SurgeryCochin Hospital, APHPParisFrance
- Université Paris CitéParisFrance
| | - Mohamed Ali Chaouch
- Department of Visceral and Digestive SurgeryMonastir University HospitalMonastirTunisia
| | - Laurent Sulpice
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- INSERM OSS U1242, University Hospital, Rennes 1 UniversityRennesFrance
| | - Michel Samson
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
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Groen PC, van Leeuwen OB, de Jonge J, Porte RJ. Viability assessment of the liver during ex-situ machine perfusion prior to transplantation. Curr Opin Organ Transplant 2024; 29:239-247. [PMID: 38764406 PMCID: PMC11224566 DOI: 10.1097/mot.0000000000001152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
PURPOSE OF REVIEW In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function. RECENT FINDINGS Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy. SUMMARY Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.
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Affiliation(s)
- Puck C Groen
- Department of Surgery, Division of Hepato-Pancreato- Biliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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Hsieh C, Hsu Y, Chen Y, Liang H, Lin K, Chen W, Wu H, Hunang S, Hung Y. Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome. Ann Gastroenterol Surg 2024; 8:312-320. [PMID: 38455485 PMCID: PMC10914688 DOI: 10.1002/ags3.12749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 08/17/2023] [Accepted: 09/29/2023] [Indexed: 03/09/2024] Open
Abstract
Aims The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. Methods We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). Results There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Conclusions Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.
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Affiliation(s)
- Chia‐En Hsieh
- Department of Nursing, Liver Transplantation CenterChung Shan Medical University HospitalTaichungTaiwan
| | - Ya‐Lan Hsu
- Department of Nursing, Liver Transplantation CenterChung Shan Medical University HospitalTaichungTaiwan
| | - Yao‐Li Chen
- Department of Surgery, Liver Transplantation CenterChung Shan Medical University HospitalTaichungTaiwan
- School of MedicineChung Shan Medical UniversityTaichungTaiwan
| | - Hsin‐Rou Liang
- Department of SurgeryKaohsiung Medical University Chung‐Ho Memorial HospitalKaohsiungTaiwan
| | - Kuo‐Hua Lin
- General SurgeryChanghua Christian HospitalChanghuaTaiwan
| | - Wen‐Yuan Chen
- Department of Pharmacy, Liver Transplantation CenterChung Shan Medical University HospitalTaichungTaiwan
| | - Hsiu‐Man Wu
- Department of NursingChanghua Christian HospitalChanghuaTaiwan
| | - Sin‐Bao Hunang
- Department of Family and Community MedicineChung Shan Medical University HospitalTaichungTaiwan
- Department of Medical Humanities, School of MedicineChung Shan Medical UniversityTaichungTaiwan
| | - Yu‐Ju Hung
- Department of Surgery, Liver Transplantation CenterChung Shan Medical University HospitalTaichungTaiwan
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Blondeel J, Blondeel M, Gilbo N, Vandervelde CM, Fieuws S, Jochmans I, Van Raemdonck D, Pirenne J, Ceulemans LJ, Monbaliu D. Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time. Transplantation 2024; 108:192-197. [PMID: 37271865 DOI: 10.1097/tp.0000000000004669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
BACKGROUND Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome. METHODS All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression). RESULTS Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival. CONCLUSIONS Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed.
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Affiliation(s)
- Joris Blondeel
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Maarten Blondeel
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Nicholas Gilbo
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Christelle M Vandervelde
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Steffen Fieuws
- Department of Public Health, Interuniversity Centre for Biostatistics and Statistical Bioinformatics, KU Leuven, Leuven, Belgium
| | - Ina Jochmans
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Dirk Van Raemdonck
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Laurens J Ceulemans
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
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Blondeel J, Gilbo N, De Bondt S, Monbaliu D. Stem cell Derived Extracellular Vesicles to Alleviate ischemia-reperfusion Injury of Transplantable Organs. A Systematic Review. Stem Cell Rev Rep 2023; 19:2225-2250. [PMID: 37548807 DOI: 10.1007/s12015-023-10573-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND The possible beneficial effects of stem cell-derived EV on ischemia-reperfusion injury (IRI) in organ transplantation have been frequently investigated; however, the source of EV, as well as the methods of isolation and administration vary widely. We conducted a systematic review to summarize current pre-clinical evidence on stem cell-derived EV therapy for IRI of transplantable organs. METHODS PubMed, Embase and Web of Science were searched from inception until August 19th, 2022, for studies on stem cell-derived EV therapy for IRI after heart, kidney, liver, pancreas, lung and intestine transplantation. The Systematic Review Center for Laboratory animal Experiments (SYRCLE) guidelines were followed to assess potential risk of bias. RESULTS The search yielded 4153 unique articles, of which 96 were retained. We identified 32 studies on cardiac IRI, 38 studies on renal IRI, 21 studies on liver IRI, four studies on lung IRI and one study on intestinal IRI. Most studies used rodent models of transient ischemic injury followed by in situ reperfusion. In all studies, EV therapy was associated with improved outcome albeit to a variable degree. EV-therapy reduced organ injury and improved function while displaying anti-inflammatory-, immunomodulatory- and pro-regenerative properties. CONCLUSION A multitude of animal studies support the potential of stem cell-derived EV-therapy to alleviate IRI after solid organ transplantation but suffer from low reporting quality and wide methodological variability. Future studies should focus on determining optimal stem cell source, dosage, and timing of treatment, as well as long-term efficacy in transplant models.
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Affiliation(s)
- Joris Blondeel
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium
| | - Nicholas Gilbo
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Surgery and Transplantation, CHU Liege, Liege, Belgium
| | | | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.
- Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium.
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Blondeel J, Gilbo N, Heedfeld V, Wylin T, Libbrecht L, Jochmans I, Pirenne J, Korf H, Monbaliu D. The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion. Int J Mol Sci 2023; 24:12831. [PMID: 37629012 PMCID: PMC10454045 DOI: 10.3390/ijms241612831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/04/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023] Open
Abstract
Although normothermic machine perfusion (NMP) provides superior preservation of liver grafts compared to static cold storage and allows for viability testing of high-risk grafts, its effect on the liver immune compartment remains unclear. We investigated the innate immune response during 6 h of continuous NMP (cNMP) of livers that were directly procured (DP, n = 5) or procured after 60 min warm ischemia (WI, n = 5), followed by 12 h of whole blood (WB) reperfusion. WI livers showed elevated transaminase levels during cNMP but not after WB reperfusion. Perfusate concentrations of TNF-α were lower in WI livers during cNMP and WB reperfusion, whereas IL-8 concentrations did not differ significantly. TGF-β concentrations were higher in WI livers during NMP but not after WB reperfusion, whereas IL-10 concentrations were similar. Endoplasmic stress and apoptotic signaling were increased in WI livers during cNMP but not after WB reperfusion. Additionally, neutrophil mobilization increased to a significantly lesser extent in WI livers at the end of NMP. In conclusion, WI livers exhibit a distinct innate immune response during cNMP compared to DP livers. The cytokine profile shifted towards an anti-inflammatory phenotype during cNMP and WB reperfusion, and pro-apoptotic signaling was stronger during cNMP. During WB reperfusion, livers exhibited a blunted cytokine release, regardless of ischemic damage, supporting the potential reconditioning effect of cNMP.
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Affiliation(s)
- Joris Blondeel
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Nicholas Gilbo
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Veerle Heedfeld
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Tine Wylin
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Louis Libbrecht
- Department of Pathology, AZ Groeninge, 8500 Kortrijk, Belgium;
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, 3000 Leuven, Belgium;
| | - Ina Jochmans
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
| | - Hannelie Korf
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, 3000 Leuven, Belgium;
| | - Diethard Monbaliu
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, 3000 Leuven, Belgium; (J.B.); (N.G.); (V.H.); (T.W.); (I.J.); (J.P.)
- Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium
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Guo Z, Zhao Q, Jia Z, Huang C, Wang D, Ju W, Zhang J, Yang L, Huang S, Chen M, Zhu X, Hu A, Ma Y, Wu L, Chen Y, Han M, Tang Y, Wang G, Wang L, Li L, Xiong W, Zhang Z, Shen Y, Tang Z, Zhu C, Chen X, Hu X, Guo Y, Chen H, Ma Y, Zhang T, Huang S, Zeng P, Lai S, Wang T, Chen Z, Gong J, Yu J, Sun C, Li C, Tan H, Liu Y, Dong Y, Sun C, Liao B, Ren J, Zhou Z, Andrea S, Björn N, Cai C, Gong F, Rong J, Huang W, Guan X, Clavien PA, Stefan TG, Huang J, He X. A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease. J Hepatol 2023; 79:394-402. [PMID: 37086919 DOI: 10.1016/j.jhep.2023.04.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 03/13/2023] [Accepted: 04/03/2023] [Indexed: 04/24/2023]
Abstract
BACKGROUND & AIMS Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.
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Affiliation(s)
- Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China; NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, China.
| | - Qiang Zhao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Zehua Jia
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Changjun Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Dongping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Weiqiang Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Jian Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510080, China
| | - Lu Yang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Shanzhou Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Maogen Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Anbin Hu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Linwei Wu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yinghua Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Ming Han
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yunhua Tang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Guodong Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Linhe Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Lifen Li
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Wei Xiong
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhiheng Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yuekun Shen
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhaoxia Tang
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Caihui Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Xiaoxiang Chen
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xiaoguang Hu
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Yiwen Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Honghui Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yihao Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Tao Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Shunwei Huang
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Ping Zeng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Simei Lai
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Tielong Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Zhitao Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Jinlong Gong
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Jia Yu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Canhui Sun
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Chang Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Haiyi Tan
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Yao Liu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Yuqi Dong
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Chengjun Sun
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Jun Ren
- Department of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Zhenhai Zhou
- Department of Blood Transfusion, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Schlegel Andrea
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, 20100, Italy
| | - Nashan Björn
- Organ Transplantation Center, The First Affiliated Hospital of the University of Science and Technology of China, Hefei, 230001, China
| | - Changjie Cai
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Fengqiu Gong
- Operating Room and Anesthesia Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Jian Rong
- Department of Cardiopulmonary Bypass, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Wenqi Huang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xiangdong Guan
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Zurich 8044, Switzerland
| | - Tullius G Stefan
- Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA
| | - Jiefu Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, 510080, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, 510080, China.
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9
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Blondeel J, Monbaliu D, Gilbo N. Dynamic liver preservation: Are we still missing pieces of the puzzle? Artif Organs 2023; 47:248-259. [PMID: 36227006 DOI: 10.1111/aor.14397] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 02/03/2023]
Abstract
To alleviate the persistent shortage of donor livers, high-risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls short in protecting these high-risk livers from ischemia-reperfusion injury, as evident from higher rates of post-transplant complications such as early allograft dysfunction and ischemic cholangiopathy. Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre-transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead.
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Affiliation(s)
- Joris Blondeel
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Nicholas Gilbo
- Department of Microbiology, Immunology and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery and Coordination, University Hospitals Leuven, Leuven, Belgium
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10
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Meurisse N, Mertens M, Fieuws S, Gilbo N, Jochmans I, Pirenne J, Monbaliu D. Effect of a Combined Drug Approach on the Severity of Ischemia-Reperfusion Injury During Liver Transplant: A Randomized Clinical Trial. JAMA Netw Open 2023; 6:e230819. [PMID: 36853611 PMCID: PMC9975910 DOI: 10.1001/jamanetworkopen.2023.0819] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/01/2023] Open
Abstract
IMPORTANCE In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant. OBJECTIVE To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury. DESIGN, SETTING, AND PARTICIPANTS This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020. INTERVENTIONS Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase. MAIN OUTCOMES AND MEASURES The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival. RESULTS Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis (median recipient age, 60 years [IQR, 51.7-66.2 years]; 52 [72.2%] men). Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L [95% CI, 946.3-1685.4 U/L] vs 1451.2 U/L [95% CI, 1087.4-1936.7 U/L]; geometric mean ratio, 0.87 [95% CI, 0.58-1.31]; P = .49) (to convert AST to μkat/L, multiply by 0.0167). There also were no significant differences in the secondary end points between the groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, the combined drug approach targeting the post-cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02251041.
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Affiliation(s)
- Nicolas Meurisse
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
- Department of Abdominal Surgery and Transplantation, CHU de Liège, University of Liège, Liège, Belgium
| | - Markoen Mertens
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Steffen Fieuws
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven—University of Leuven, Leuven, Belgium
| | - Nicholas Gilbo
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Ina Jochmans
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Abdominal Transplant Surgery and Transplant Coordination, University Hospitals Leuven, Leuven, Belgium
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11
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Cannon RM, Nassel AF, Walker JT, Sheikh SS, Orandi BJ, Lynch RJ, Shah MB, Goldberg DS, Locke JE. Lost potential and missed opportunities for DCD liver transplantation in the United States. Am J Surg 2022; 224:990-998. [PMID: 35589438 PMCID: PMC9940905 DOI: 10.1016/j.amjsurg.2022.05.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 04/20/2022] [Accepted: 05/03/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Donation after cardiac death(DCD) has been proposed as an avenue to expand the liver donor pool. METHODS We examined factors associated with nonrecovery of DCD livers using UNOS data from 2015 to 2019. RESULTS There 265 non-recovered potential(NRP) DCD livers. Blood type AB (7.8% vs. 1.1%) and B (16.9% vs. 9.8%) were more frequent in the NRP versus actual donors (p < 0.001). The median driving time between donor hospital and transplant center was similar for NRP and actual donors (30.1 min vs. 30.0 min; p = 0.689), as was the percentage located within a transplant hospital (20.8% vs. 20.9%; p = 0.984).The donation service area(DSA) of a donor hospital explained 27.9% (p = 0.001) of the variability in whether a DCD liver was recovered. CONCLUSION A number of potentially high quality DCD donor livers go unrecovered each year, which may be partially explained by donor blood type and variation in regional and DSA level practice patterns.
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Affiliation(s)
- Robert M Cannon
- Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA.
| | - Ariann F Nassel
- Lister Hill Center for Health Policy, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jeffery T Walker
- Center for the Study of Community Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Saulat S Sheikh
- Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Babak J Orandi
- Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Raymond J Lynch
- Department of Surgery, Division of Transplantation, Emory University, Atlanta, GA, USA
| | - Malay B Shah
- Department of Surgery, Division of Transplantation, University of Kentucky, Lexington, KY, USA
| | - David S Goldberg
- Department of Medicine, Division of Digestive Health and Liver Diseases, University of Miami, Miami, FL, USA
| | - Jayme E Locke
- Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA
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12
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Ziogas IA, Kakos CD, Esagian SM, Skarentzos K, Alexopoulos SP, Shingina A, Montenovo MI. Liver transplant after donation from controlled circulatory death versus brain death: A UNOS database analysis and publication bias adjusted meta-analysis. Clin Transplant 2021; 36:e14521. [PMID: 34689372 DOI: 10.1111/ctr.14521] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/06/2021] [Accepted: 10/16/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Donation after circulatory death (DCD) is an increasingly utilized alternative to donation after brain death (DBD) to expand the liver donor pool. We compared the outcomes of liver transplant (LT) after DCD versus DBD. METHODS A PRISMA-compliant systematic literature review was performed using the PubMed, Cochrane Library, and Embase databases (end-of-search-date: July 2, 2020). US outcomes were analyzed using the UNOS database (February, 2002-September, 2020). Pooled hazard ratios (HR) for patient and graft survival were obtained through random effect meta-analyses and adjusted for publication bias. RESULTS Thirteen studies reporting on 1426 DCD and 5385 DBD LT recipients were included. 5620 DCD and 87561 DBD LT recipients were analyzed from the UNOS database. Meta-analysis showed increased risk of patient mortality for DCD (HR = 1.36; 95%CI, 1.09-1.70; P = .01; I2 = 53.6%). When adjusted for publication bias, meta-analysis showed no difference in patient survival between DCD and DBD (HR = 1.15; 95%CI, .91-1.45; P = .25; I2 = 61.5%). Meta-analysis showed increased risk of graft loss for DCD (HR = 1.50; 95%CI, 1.20-1.88; P < .001; I2 = 67.8%). When adjusted for publication bias, meta-analysis showed a reduction in effect size (HR = 1.36; 95%CI, 1.06-1.74; P = .02; I2 = 73.5%). CONCLUSION When adjusted for publication bias, no difference was identified between DCD and DBD regarding patient survival, while DCD was associated with an increased risk of graft loss.
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Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.,Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Christos D Kakos
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | - Stepan M Esagian
- Surgery Working Group, Society of Junior Doctors, Athens, Greece
| | | | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Alexandra Shingina
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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13
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Schlegel A, Foley DP, Savier E, Flores Carvalho M, De Carlis L, Heaton N, Taner CB. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation. Transplantation 2021; 105:1892-1903. [PMID: 34416750 DOI: 10.1097/tp.0000000000003825] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - David P Foley
- University of Wisconsin School of Medicine and Public Health, William S. Middleton VA Medical Center, Madison, WI
| | - Eric Savier
- Department of Hepatobiliary Surgery and Liver Transplantation, Sorbonne Université Pitié-Salpêtrière Hospital, Paris, France
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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14
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Early Allograft Dysfunction and Complications in DCD Liver Transplantation: Expert Consensus Statements From the International Liver Transplantation Society. Transplantation 2021; 105:1643-1652. [PMID: 34291765 DOI: 10.1097/tp.0000000000003877] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Livers for transplantation from donation after circulatory death donors are relatively more prone to early and ongoing alterations in graft function that might ultimately lead to graft loss and even patient death. In consideration of this fact, this working group of the International Liver Transplantation Society has performed a critical evaluation of the medical literature to create a set of statements regarding the assessment of early allograft function/dysfunction and complications arising in the setting of donation after circulatory death liver transplantation.
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van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N, van Hoek B, Huurman VAL, Jochmans I, van Leeuwen OB, de Meijer VE, Monbaliu D, Polak WG, Slangen JJG, Troisi RI, Vanlander A, de Jonge J, Porte RJ. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial. N Engl J Med 2021; 384:1391-1401. [PMID: 33626248 DOI: 10.1056/nejmoa2031532] [Citation(s) in RCA: 379] [Impact Index Per Article: 94.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
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Affiliation(s)
- Rianne van Rijn
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Ivo J Schurink
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Yvonne de Vries
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Aad P van den Berg
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Miriam Cortes Cerisuelo
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Sarwa Darwish Murad
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Joris I Erdmann
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Nicholas Gilbo
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Robbert J de Haas
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Nigel Heaton
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Bart van Hoek
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Volkert A L Huurman
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Ina Jochmans
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Otto B van Leeuwen
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Vincent E de Meijer
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Diethard Monbaliu
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Wojciech G Polak
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Jules J G Slangen
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Roberto I Troisi
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Aude Vanlander
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Jeroen de Jonge
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
| | - Robert J Porte
- From the Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation (R.R., Y.V., O.B.L., V.E.M., R.J.P.), the Departments of Gastroenterology and Hepatology (A.P.B.) and Radiology (R.J.H., J.J.G.S.), University of Groningen, University Medical Center Groningen, Groningen, the Departments of Surgery (I.J.S., W.G.P., J.J.) and Gastroenterology and Hepatology (S.D.M.), Erasmus University Medical Center, Rotterdam, and the Departments of Surgery (J.I.E., V.A.L.H.) and Gastroenterology and Hepatology (B.H.), Leiden University Medical Center, Leiden - all in the Netherlands; the Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London (M.C.C., N.H.); the Transplantation Research Group, the Department of Microbiology, Immunology, and Transplantation, Katholieke Universiteit Leuven, and the Department of Abdominal Transplantation Surgery and Coordination, University Hospitals Leuven, Leuven (N.G., I.J., D.M.), and the Department of Transplant Surgery, Ghent University Hospital, Ghent (R.I.T., A.V.) - both in Belgium
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16
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Panconesi R, Flores Carvalho M, Mueller M, Meierhofer D, Dutkowski P, Muiesan P, Schlegel A. Viability Assessment in Liver Transplantation-What Is the Impact of Dynamic Organ Preservation? Biomedicines 2021; 9:161. [PMID: 33562406 PMCID: PMC7915925 DOI: 10.3390/biomedicines9020161] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/02/2021] [Accepted: 02/03/2021] [Indexed: 02/07/2023] Open
Abstract
Based on the continuous increase of donor risk, with a majority of organs classified as marginal, quality assessment and prediction of liver function is of utmost importance. This is also caused by the notoriously lack of effective replacement of a failing liver by a device or intensive care treatment. While various parameters of liver function and injury are well-known from clinical practice, the majority of specific tests require prolonged diagnostic time and are more difficult to assess ex situ. In addition, viability assessment of procured organs needs time, because the development of the full picture of cellular injury and the initiation of repair processes depends on metabolic active tissue and reoxygenation with full blood over several hours or days. Measuring injury during cold storage preservation is therefore unlikely to predict the viability after transplantation. In contrast, dynamic organ preservation strategies offer a great opportunity to assess organs before implantation through analysis of recirculating perfusates, bile and perfused liver tissue. Accordingly, several parameters targeting hepatocyte or cholangiocyte function or metabolism have been recently suggested as potential viability tests before organ transplantation. We summarize here a current status of respective machine perfusion tests, and report their clinical relevance.
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Affiliation(s)
- Rebecca Panconesi
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, 50134 Florence, Italy; (R.P.); (M.F.C.); (P.M.)
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, 50134 Florence, Italy; (R.P.); (M.F.C.); (P.M.)
| | - Matteo Mueller
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, 8091 Zurich, Switzerland; (M.M.); (P.D.)
| | - David Meierhofer
- Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, 14195 Berlin, Germany;
| | - Philipp Dutkowski
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, 8091 Zurich, Switzerland; (M.M.); (P.D.)
| | - Paolo Muiesan
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, 50134 Florence, Italy; (R.P.); (M.F.C.); (P.M.)
| | - Andrea Schlegel
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, 50134 Florence, Italy; (R.P.); (M.F.C.); (P.M.)
- Department of Visceral Surgery and Transplantation, University Hospital Zurich, Swiss HPB and Transplant Center, 8091 Zurich, Switzerland; (M.M.); (P.D.)
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17
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Little CJ, Dick AAS, Perkins JD, Hsu EK, Reyes JD. Livers From Pediatric Donation After Circulatory Death Donors Represent a Viable and Underutilized Source of Allograft. Liver Transpl 2020; 26:1138-1153. [PMID: 32403205 DOI: 10.1002/lt.25795] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/16/2020] [Accepted: 05/04/2020] [Indexed: 01/13/2023]
Abstract
Despite increased numbers of donation after circulatory death (DCD) donors, pediatric DCD livers are underused. To investigate possible reasons for this discrepancy, we conducted a retrospective cohort study using 2 data sets from the Organ Procurement and Transplantation Network for all deceased liver donors and for all recipients of DCD liver transplants from March 8, 1993, to June 30, 2018. Pediatric (0-12 years) and adolescent (13-17 years) DCD donors were compared with those aged 18-40 years. We found that pediatric DCD allografts are recovered at a significantly lower rate than from 18-to-40-year-old donors (27.3% versus 56.3%; P < 0.001). However, once recovered, these organs are transplanted at a similar rate to those from the 18-to-40-year-old donor cohort (74.7% versus 74.2%). Significantly more pediatric DCD livers (odds ratio [OR], 3.75; confidence interval [CI], 3.14-4.47) were not recovered compared with adult organs, which were most commonly not recovered due to organ quality (10.2% versus 7.1%; P < 0.001). The 10-year relative risks (RRs) for graft failure and patient death were similar between pediatric and adult DCD donors, with adolescent DCD livers demonstrating improved outcomes. DCD livers transplanted into pediatric donors were protective against graft failure (RR, 0.46; 95% confidence interval [CI], 0.21-0.99) and patient death (RR, 0.16; 95% CI, 0.04-0.69). In conclusion, despite lower rates of recovery, pediatric DCD livers represent a viable organ source for certain adults and children.
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Affiliation(s)
| | - Andre A S Dick
- Division of Transplantation, University of Washington Medical Center, Seattle, WA.,Seattle Children's Hospital, Section of Pediatric Transplantation, Seattle, WA
| | - James D Perkins
- Division of Transplantation, University of Washington Medical Center, Seattle, WA
| | - Evelyn K Hsu
- Division of Gastroenterology, Department of Pediatrics, University of Washington Medical Center, Seattle, WA
| | - Jorge D Reyes
- Division of Transplantation, University of Washington Medical Center, Seattle, WA.,Seattle Children's Hospital, Section of Pediatric Transplantation, Seattle, WA
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18
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Hann A, Osei-Bordom DC, Neil DAH, Ronca V, Warner S, Perera MTPR. The Human Immune Response to Cadaveric and Living Donor Liver Allografts. Front Immunol 2020; 11:1227. [PMID: 32655558 PMCID: PMC7323572 DOI: 10.3389/fimmu.2020.01227] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 05/15/2020] [Indexed: 12/13/2022] Open
Abstract
The liver is an important contributor to the human immune system and it plays a pivotal role in the creation of both immunoreactive and tolerogenic conditions. Liver transplantation provides the best chance of survival for both children and adults with liver failure or cancer. With current demand exceeding the number of transplantable livers from donors following brain death, improved knowledge, technical advances and the desire to prevent avoidable deaths has led to the transplantation of organs from living, ABO incompatible (ABOi), cardiac death donors and machine based organ preservation with acceptable results. The liver graft is the most well-tolerated, from an immunological perspective, of all solid organ transplants. Evidence suggests successful cessation of immunosuppression is possible in ~20–40% of liver transplant recipients without immune mediated graft injury, a state known as “operational tolerance.” An immunosuppression free future following liver transplantation is an ambitious but perhaps not unachievable goal. The initial immune response following transplantation is a sterile inflammatory process mediated by the innate system and the mechanisms relate to the preservation-reperfusion process. The severity of this injury is influenced by graft factors and can have significant consequences. There are minimal experimental studies that delineate the differences in the adaptive immune response to the various forms of liver allograft. Apart from ABOi transplants, antibody mediated hyperacute rejection is rare following liver transplant. T-cell mediated rejection is common following liver transplantation and its incidence does not differ between living or deceased donor grafts. Transplantation in the first year of life results in a higher rate of operational tolerance, possibly due to a bias toward Th2 cytokines (IL4, IL10) during this period. This review further describes the current understanding of the immunological response toward liver allografts and highlight the areas of this topic yet to be fully understood.
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Affiliation(s)
- Angus Hann
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | | | - Desley A H Neil
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Vincenzo Ronca
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Suz Warner
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,The Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom
| | - M Thamara P R Perera
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.,The Liver Unit, Birmingham Children's Hospital, Birmingham, United Kingdom
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19
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Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers. Transplantation 2020; 103:1405-1413. [PMID: 30395120 PMCID: PMC6613725 DOI: 10.1097/tp.0000000000002500] [Citation(s) in RCA: 123] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers before implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI). METHODS In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cutoff values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n = 6) to identify transplantable liver grafts with low BDI. RESULTS Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared with high BDI. The following cutoff values were associated with low BDI: biliary bicarbonate greater than 18 mmol/L (P = 0.002), biliary pH greater than 7.48 (P = 0.019), biliary glucose less than 16 mmol/L (P = 0.013), and bile/perfusate glucose ratio less than 0.67 (P = 0.013). In the clinical trial, 4 of 6 livers met these criteria and were transplanted, and none developed clinical evidence of posttransplant cholangiopathy. CONCLUSIONS Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point of care, making them suitable for the pretransplant assessment of bile duct viability. This may improve graft selection and decrease the risk of posttransplant cholangiopathy.
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20
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Matton APM, Selten JW, Roest HP, de Jonge J, IJzermans JNM, de Meijer VE, Porte RJ, van der Laan LJW. Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers. Clin Transplant 2020; 34:e13790. [PMID: 31984571 PMCID: PMC7154637 DOI: 10.1111/ctr.13790] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 12/20/2019] [Accepted: 01/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. METHODS Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. RESULTS Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. CONCLUSION Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion.
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Affiliation(s)
- Alix P. M. Matton
- Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
- Surgical Research LaboratoryDepartment of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Jasmijn W. Selten
- Department of SurgeryErasmus MC – University Medical Center RotterdamRotterdamThe Netherlands
| | - Henk P. Roest
- Department of SurgeryErasmus MC – University Medical Center RotterdamRotterdamThe Netherlands
| | - Jeroen de Jonge
- Department of SurgeryErasmus MC – University Medical Center RotterdamRotterdamThe Netherlands
| | - Jan N. M. IJzermans
- Department of SurgeryErasmus MC – University Medical Center RotterdamRotterdamThe Netherlands
| | - Vincent E. de Meijer
- Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Robert J. Porte
- Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity Medical Center GroningenUniversity of GroningenGroningenThe Netherlands
| | - Luc J. W. van der Laan
- Department of SurgeryErasmus MC – University Medical Center RotterdamRotterdamThe Netherlands
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21
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Cascales-Campos PA, Ferreras D, Alconchel F, Febrero B, Royo-Villanova M, Martínez M, Rodríguez JM, Fernández-Hernández JÁ, Ríos A, Pons JA, Sánchez-Bueno F, Robles R, Martínez-Barba E, Martínez-Alarcón L, Parrilla P, Ramírez P. Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again. Am J Transplant 2020; 20:204-212. [PMID: 31329359 DOI: 10.1111/ajt.15537] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/20/2019] [Accepted: 07/09/2019] [Indexed: 01/25/2023]
Abstract
Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD-LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD-LT immediately after each DCD-LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut-off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.
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Affiliation(s)
- Pedro A Cascales-Campos
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - David Ferreras
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Felipe Alconchel
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Beatriz Febrero
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Mario Royo-Villanova
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
- Intensive Care Unit, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - María Martínez
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
- Intensive Care Unit, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - José M Rodríguez
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Juan Á Fernández-Hernández
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Antonio Ríos
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - José A Pons
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
- Department of Hepatology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Francisco Sánchez-Bueno
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Ricardo Robles
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Enrique Martínez-Barba
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
- Department of Patholoy, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Laura Martínez-Alarcón
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Pascual Parrilla
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
| | - Pablo Ramírez
- Department of Surgery, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
- Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
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22
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Pietersen LC, Sarton E, Alwayn I, Lam HD, Putter H, van Hoek B, Braat AE. Impact of Temporary Portocaval Shunting and Initial Arterial Reperfusion in Orthotopic Liver Transplantation. Liver Transpl 2019; 25:1690-1699. [PMID: 31276282 DOI: 10.1002/lt.25592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 06/06/2019] [Indexed: 01/13/2023]
Abstract
The use of a temporary portocaval shunt (TPCS) as well as the order of reperfusion (initial arterial reperfusion [IAR] versus initial portal reperfusion) in orthotopic liver transplantation (OLT) is controversial and, therefore, still under debate. The aim of this study was to evaluate outcome for the 4 possible combinations (temporary portocaval shunt with initial arterial reperfusion [A+S+], temporary portocaval shunt with initial portal reperfusion, no temporary portocaval shunt with initial arterial reperfusion, and no temporary portocaval shunt with initial portal reperfusion) in a center-based cohort study, including liver transplantations (LTs) from both donation after brain death and donation after circulatory death (DCD) donors. The primary outcome was the perioperative transfusion of red blood cells (RBCs), and the secondary outcomes were operative time and patient and graft survival. Between January 2005 and May 2017, all first OLTs performed in our institution were included in the 4 groups mentioned. With IAR and TPCS, a significantly lower perioperative transfusion of RBCs was seen (P < 0.001) as well as a higher number of recipients without any transfusion of RBCs (P < 0.001). A multivariate analysis showed laboratory Model for End-Stage Liver Disease (MELD) score (P < 0.001) and IAR (P = 0.01) to be independent determinants of the transfusion of RBCs. When comparing all groups, no statistical difference was seen in operative time or in 1-year patient and graft survival rates despite more LTs with a liver from a DCD donor in the A+S+ group (P = 0.005). In conclusion, next to a lower laboratory MELD score, the use of IAR leads to a significantly lower need for perioperative blood transfusion. There was no significant interaction between IAR and TPCS. Furthermore, the use of a TPCS and/or IAR does not lead to increased operative time and is therefore a reasonable alternative surgical strategy.
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Affiliation(s)
- Lars Cornelis Pietersen
- Division of Transplantation, Departments of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Elise Sarton
- Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Ian Alwayn
- Division of Transplantation, Departments of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Hwai-Ding Lam
- Division of Transplantation, Departments of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Hein Putter
- Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands
| | - Bart van Hoek
- Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Andries Erik Braat
- Division of Transplantation, Departments of Surgery, Leiden University Medical Center, Leiden, the Netherlands
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23
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Meurisse N, Monbaliu D, Berlakovich G, Muiesan P, Oliverius M, Adam R, Pirenne J. Heterogeneity of Bile Duct Management in the Development of Ischemic Cholangiopathy After Liver Transplantation: Results of a European Liver and Intestine Transplant Association Survey. Transplant Proc 2019; 51:1926-1933. [PMID: 31301856 DOI: 10.1016/j.transproceed.2019.04.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 04/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Surgical factors and direct cytotoxicity of bile salts on cholangiocytes may play a role in the development of ischemic cholangiopathy (IC) after liver transplantation (LTx). There is no validated consensus on how to protect the bile ducts during procurement, static preservation, and LTx. Meanwhile, IC remains the most troublesome complication after LTx. AIM To characterize bile duct management techniques during the LTx process among European transplant centers in cases of donation after brain death (DBD) and circulatory death (DCD). METHOD An European Liver and Intestine Transplant Association-European Liver Transplant Registry web survey designed to conceal respondents' personal information was sent to surgeons procuring and/or transplanting livers in Europe. RESULTS Sixty-five percent of responses came from large transplant centers (>50 procurements/y). In 8% of DBDs and 14% of DCDs the bile duct is not rinsed. In 46% of DBDs and 52% of DCDs surgeons prefer to remove the gallbladder after graft reperfusion. Protocols concerning preservation solutions (nature, pressure, volume) are extremely heterogeneous. In 54% of DBDs and 61% of DCDs an arterial back table pressure perfusion is performed. Steroids (20%-10%), heparin (72%-60%), prostacyclin (3%-7%), and fibrinolytics (4%-11%) are used as donor-protective interventions in DBD and DCD cases, respectively. In 2% of DBD and 6% of DCD cases a hepatic artery reperfusion is performed first. In 4% of DBD and 6% of DCD cases, fibrinolytics are administered through the hepatic artery during the bench and/or implantation. CONCLUSION This European web survey shows for the first time the heterogeneity in the management of bile ducts during procurement, preservation, and transplantation in Europe. In the context of sharing more marginal liver grafts, an expert meeting must be organized to formulate guidelines to be applied to protect liver grafts against IC.
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Affiliation(s)
- Nicolas Meurisse
- Department of Abdominal Transplant Surgery, University of Liege Academic Hospital, ULg CHU, Liege, Belgium; Department of Abdominal Transplant Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Gabriela Berlakovich
- Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Paolo Muiesan
- Liver Unit, University of Birmingham, Birmingham, United Kingdom
| | - Martin Oliverius
- Department of Surgery of the 3rd Faculty of Medicine Charles University and Kralovske Vinohrady Hospital, Prague, Czech Republic
| | - René Adam
- APHP Hospital Paul Brousse, Inserm U985, University Paris Sud, Paris, France
| | - Jacques Pirenne
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
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24
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Franchitto A, Overi D, Mancinelli R, Mitterhofer AP, Muiesan P, Tinti F, Umbro I, Hubscher SG, Onori P, Gaudio E, Carpino G. Peribiliary gland damage due to liver transplantation involves peribiliary vascular plexus and vascular endothelial growth factor. Eur J Histochem 2019; 63:3022. [PMID: 31113191 PMCID: PMC6517787 DOI: 10.4081/ejh.2019.3022] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 04/23/2019] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic bile ducts are characterized by the presence of peribiliary glands (PBGs), which represent stem cell niches implicated in biliary regeneration. Orthotopic liver transplantation may be complicated by non-anastomotic strictures (NAS) of the bile ducts, which have been associated with ischemic injury of PBGs and occur more frequently in livers obtained from donors after circulatory death than in those from brain-dead donors. The aims of the present study were to investigate the PBG phenotype in bile ducts after transplantation, the integrity of the peribiliary vascular plexus (PVP) around PBGs, and the expression of vascular endothelial growth factor-A (VEGF-A) by PBGs. Transplanted ducts obtained from patients who underwent liver transplantation were studied (N=62). Controls included explanted bile duct samples not used for transplantation (N=10) with normal histology. Samples were processed for histology, immunohistochemistry and immunofluorescence. Surface epithelium is severely injured in transplanted ducts; PBGs are diffusely damaged, particularly in ducts obtained from circulatory-dead compared to brain-dead donors. PVP is reduced in transplanted compared to controls. PBGs in transplanted ducts contain more numerous progenitor and proliferating cells compared to controls, show higher positivity for VEGF-A compared to controls, and express VEGF receptor-2. In conclusion, PBGs and associated PVP are damaged in transplanted extrahepatic bile ducts; however, an activation of the PBG niche takes place and is characterized by proliferation and VEGF-A expression. This response could have a relevant role in reconstituting biliary epithelium and vascular plexus and could be implicated in the genesis of non-anastomotic strictures.
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Affiliation(s)
- Antonio Franchitto
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome.
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Vivalda S, Zhengbin H, Xiong Y, Liu Z, Wang Z, Ye Q. Vascular and Biliary Complications Following Deceased Donor Liver Transplantation: A Meta-analysis. Transplant Proc 2019; 51:823-832. [PMID: 30979471 DOI: 10.1016/j.transproceed.2018.11.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 11/15/2018] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To assess biliary and vascular complications after liver transplantations (LTs) sourced from deceased donors. METHODS This study reviewed potentially relevant English-language articles gathered from PubMed and Medline published from 2012 to 2017. One additional study was carried out using our institution's database for articles published from 2013 to 2017. Biliary and vascular complications from adult patients receiving their first deceased-donor LT were included. This meta-analysis was performed using Review Manager version 5.2 (Cochrane Collaboration, Copenhagen, Denmark) and the study quality was evaluated using the Newcastle-Ottawa Scale. RESULTS Ten studies met our inclusion criteria. Heterogeneity in donation after cardiac death (DCD) and donation after brain death (DBD) recipients was observed and minimized after pooling a subgroup analysis. This latter analysis focused on biliary stricture, biliary leaks and stones, and vascular thrombosis and stenosis. Meta-analyses showed that patients receiving DCD organs have a greatly increased risk of biliary complications compared to those receiving DBD organs, particularly the following: biliary leaks and stones (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.22-2.34); and biliary stricture (OR = 1.58, 95% CI 1.21-2.06). DCD grafts tended to be but were not significantly associated with DBD regarding vascular thrombosis (OR = 1.62, 95% CI 1.05-2.50), and the risk of vascular stenosis in DCD grafts was not statistically significant (OR = 1.25, 95% CI, .70-2.25). CONCLUSION DCD was associated with an increased risk of biliary complications after LT, tended to indicate an increased risk of vascular thrombosis versus, and was not associated with an increased risk of vascular stenosis compared to DBD. There was no significant difference between the grafts.
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Affiliation(s)
- S Vivalda
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - H Zhengbin
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Y Xiong
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Z Liu
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Z Wang
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Q Ye
- Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital, Wuhan University, Wuhan, China; Transplantation Medicine Engineering and Technology Research Center, National Health Commission, the 3rd Xiangya Hospital of Central South University, Changsha, China.
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26
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van Rijn R, van den Berg AP, Erdmann JI, Heaton N, van Hoek B, de Jonge J, Leuvenink HGD, Mahesh SVK, Mertens S, Monbaliu D, Muiesan P, Perera MTPR, Polak WG, Rogiers X, Troisi RI, de Vries Y, Porte RJ. Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial. BMC Gastroenterol 2019; 19:40. [PMID: 30866837 PMCID: PMC6416838 DOI: 10.1186/s12876-019-0956-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 02/22/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. METHODS This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. DISCUSSION DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. TRIAL REGISTRATION The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283 .
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Affiliation(s)
- Rianne van Rijn
- Section Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Aad P. van den Berg
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Joris I. Erdmann
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Nigel Heaton
- Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London, UK
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Henri G. D. Leuvenink
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Shekar V. K. Mahesh
- Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Sarah Mertens
- Department of Abdominal Transplantation Surgery, University Hospitals of Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplantation Surgery, University Hospitals of Leuven, Leuven, Belgium
| | - Paolo Muiesan
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M. Thamara P. R. Perera
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Wojciech G. Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Xavier Rogiers
- Department of Transplant Surgery, Ghent University Hospital, Ghent, Belgium
| | - Roberto I. Troisi
- Department of Transplant Surgery, Ghent University Hospital, Ghent, Belgium
| | - Yvonne de Vries
- Section Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J. Porte
- Section Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
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Outcomes of Controlled Donation After Cardiac Death Compared With Donation After Brain Death in Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Proc 2018; 50:33-41. [PMID: 29407328 DOI: 10.1016/j.transproceed.2017.11.034] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/29/2017] [Accepted: 11/19/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Controlled donation after cardiac death (CDCD) is increasingly common for liver transplantation due to donor shortage. However, the outcomes, in terms of grafts and recipients, remain unclear. The current study is a systematic review and meta-analysis that compared CDCD with donation after brain death (DBD). METHODS We conducted an electronic search of MEDLINE, EMBASE, and the Cochrane Database (from January 2007 to May 2017). Studies reporting Maastricht category III or IV CDCD liver transplantation were screened for inclusion. We appraised studies using the Newcastle-Ottawa scale and meta-analyzed using a fixed or random effects model. RESULTS A total of 21 studies, with 12,035 patients, were included in data analysis. CDCD did not differ from DBD in patient survival (hazard ration: 1.20; 95% confidence interval [CI]: 0.98 to 1.47; P = .07), graft survival (hazard ratio: 1.24; 95% CI: 0.99 to 1.56; P = .06), primary nonfunction (odds ratio [OR]: 1.74; 95% CI: 1.00 to 3.03; P = .05), hepatic artery thrombosis (OR: 1.17; 95% CI: 0.78 to 1.74; P = .45). However, CDCD was associated with biliary complications (OR: 2.48; 95% CI: 2.05 to 3.00), retransplantation (OR: 2.54; 95% CI: 1.99 to 3.26), and peak alanine aminotransferase (weighted mean difference: 330.88; 95% CI: 259.88 to 401.87). A subgroup analysis that included only hepatitis C virus (HCV)-positive recipients showed no significant difference between CDCD and DBD in biliary complications (P = .16), retransplantion (P = .15), HCV recurrence (P = .20), and peak alanine aminotransferase (P = .06). CONCLUSIONS CDCD transplantation is the most viable alternative to DBD transplantation in the current critical shortage of liver organs. HCV infection may not be the inferior factor of postoperative outcomes and survival.
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Ramirez P, Ferreras D, Febrero B, Royo M, Cascales P, Rodriguez JM, Rios A, Fernandez JA, González MR, Sanchez-Bueno F, Robles R, Parrilla P. Outcomes of Liver Transplantation Using Older Donors After Circulatory Death and the Super-Rapid Technique: 14 Cases. Transplant Proc 2018; 50:601-604. [PMID: 29579864 DOI: 10.1016/j.transproceed.2017.11.037] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 10/22/2017] [Accepted: 11/11/2017] [Indexed: 01/14/2023]
Abstract
INTRODUCTION Donation after circulatory death (DCD) has increased in the last decade, although a slight increase in surgical complications has been reported in liver transplantation (LT). Therefore, DCD is not recommended with donors aged 60 years or more because it entails an added risk. However, donation after brain death (DBD)-LT with donors aged 70 years or more shows acceptable results. OBJECTIVE The objective was to analyze the characteristics and complications of DCD-LT with donors aged 70 years or more (DCD-70). MATERIALS AND METHODS We included 14 DCD-70-LT and compared them with a control group of 28 DBD-LT aged 70 years or more. STATISTICAL ANALYSIS A descriptive analysis, Mann-Whitney U test, and Pearson chi-square or Fisher test were performed when appropriate. RESULTS Significant differences were found in aminotransferase peak at 24 hours, with an increase in the DCD-70 group (aspartate aminotransferease [AST] 1038 vs 507, P = .013; alanine aminotransferase [ALT] 750 vs 399, P = .014). The cold ischemia time was lower in DCD-70 although without significant differences (4.8 vs 6.7 hours). Biliary complications (28.6% vs 31.7%) and vascular complications (7.1% vs 7.1%) were similar. A single transplant with DCD-70 required a retransplantation due to arterial thrombosis. Mortality was the same in both cases (14.3%). CONCLUSION LT results with DCD-70 are similar to those of DBD-70, so the age criteria could also be extended in this type of donation.
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Affiliation(s)
- P Ramirez
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - D Ferreras
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - B Febrero
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain.
| | - M Royo
- Transplant Unit, Intensive Care Unit, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - P Cascales
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - J M Rodriguez
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - A Rios
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - J A Fernandez
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - M R González
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - F Sanchez-Bueno
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - R Robles
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - P Parrilla
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
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Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes. Transplantation 2017; 100:1513-24. [PMID: 27014794 DOI: 10.1097/tp.0000000000001175] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. METHODS Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. RESULTS Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. CONCLUSIONS Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.
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Eren EA, Latchana N, Beal E, Hayes D, Whitson B, Black SM. Donations After Circulatory Death in Liver Transplant. EXP CLIN TRANSPLANT 2016; 14:463-470. [PMID: 27733105 PMCID: PMC5461820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
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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Affiliation(s)
- Emre A. Eren
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Latchana
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Eliza Beal
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Don Hayes
- Departments of Pediatrics and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Section of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Bryan Whitson
- Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Sylvester M. Black
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Blok JJ, Detry O, Putter H, Rogiers X, Porte RJ, van Hoek B, Pirenne J, Metselaar HJ, Lerut JP, Ysebaert DK, Lucidi V, Troisi RI, Samuel U, den Dulk AC, Ringers J, Braat AE. Longterm results of liver transplantation from donation after circulatory death. Liver Transpl 2016; 22:1107-14. [PMID: 27028896 DOI: 10.1002/lt.24449] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 03/05/2016] [Accepted: 03/09/2016] [Indexed: 12/13/2022]
Abstract
Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107-1114 2016 AASLD.
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Affiliation(s)
- Joris J Blok
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, Liège, Belgium
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Xavier Rogiers
- Department of Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Robert J Porte
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Jacques Pirenne
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jan P Lerut
- Starzl Unit of Abdominal Transplantation, Department of Abdominal Surgery and Transplantation, University Hospitals Saint Luc, Brussels, Belgium
| | - Dirk K Ysebaert
- Department of Hepatobiliary, Transplantation and Endocrine Surgery, Antwerp University Hospital, Antwerp University, Belgium
| | - Valerio Lucidi
- Department of Abdominal Surgery, Hepatobiliary and Liver Transplantation Unit, Erasme Hospital ULB, Brussels, Belgium
| | - Roberto I Troisi
- Department of Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Undine Samuel
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - A Claire den Dulk
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Jan Ringers
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Andries E Braat
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
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Op den Dries S, Karimian N, Westerkamp AC, Sutton ME, Kuipers M, Wiersema-Buist J, Ottens PJ, Kuipers J, Giepmans BN, Leuvenink HGD, Lisman T, Porte RJ. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transpl 2016; 22:994-1005. [PMID: 26946466 DOI: 10.1002/lt.24436] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Revised: 02/04/2016] [Accepted: 02/14/2016] [Indexed: 12/21/2022]
Abstract
Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.
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Affiliation(s)
- Sanna Op den Dries
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Negin Karimian
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Andrie C Westerkamp
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Michael E Sutton
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Michiel Kuipers
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Janneke Wiersema-Buist
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Petra J Ottens
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jeroen Kuipers
- Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ben N Giepmans
- Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Henri G D Leuvenink
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Guo M, Yao D, Li L, Lu C, Li Y, Li J. Intestinal Conditioning After Cardiac Arrest: The Use of Normothermic Extracorporeal Membrane Oxygenation in the Non-Heart-Beating Animal Model. Artif Organs 2016; 40:738-45. [PMID: 27097758 DOI: 10.1111/aor.12691] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 12/03/2015] [Accepted: 12/11/2015] [Indexed: 12/12/2022]
Abstract
The effect of normothermic extracorporeal membrane oxygenation (NECMO) on small bowel preservation in a clinically relevant large animal model of expected donation after cardiac death (eDCD) was evaluated. Thirty domestic crossbred donor pigs were divided into five groups. The first group served as the live donation (LD) group, the second group served as the donation after cardiac death (DCD) group, and the remaining were further assigned into three subgroups: E1 group (1 h NECMO support), E3 group (3 h NECMO support), and E5 group (5 h NECMO support). Pathology, electron microscopy, energy metabolism, cell apoptosis, and tight junction (TJ) protein expression level of intestinal mucosa and the level of plasma d-lactic acid were evaluated in normal, cardiac death and at the end of extracorporeal support, respectively. The mean arterial pressure and PaO2 were maintained over 60 and 267 mm Hg during NECMO support, respectively. One hour of extracorporeal support could improve the energy status in intestines of the DCD group. Although the histologic damage and apoptosis of the E1 group had no significant difference with those of the LD and DCD groups (P > 0.05), the levels of intestinal mucosa TJ protein decreased (P < 0.05), and plasma d-lactic acid increased progressively (P < 0.05). With the extension of extracorporeal support, the degree of intestinal mucosa damage and intestinal permeability gradually increased, as well as the content of adenosine triphosphate in intestinal mucosa. The normothermic extracorporeal support for 1 h in DCD is beneficial for improving the energy status and viability of the bowel. However, the integrity of intestinal mucosa was destroyed gradually as extracorporeal support time went by. And the activation of intestinal epithelial apoptosis and hyperoxia might be the factors that lead to intestinal mucosa injury.
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Affiliation(s)
- Mingxiao Guo
- Department of Laparoscopic Surgery Center, Linyi People's Hospital, Shandong University, Linyi
| | - Danhua Yao
- Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing
| | - Linlin Li
- Department of Surgery, Linyi Mental Health Center, Linyi, China
| | - Chunlei Lu
- Department of Laparoscopic Surgery Center, Linyi People's Hospital, Shandong University, Linyi
| | - Yousheng Li
- Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing
| | - Jieshou Li
- Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing
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Chirichella TJ, Dunham CM, Zimmerman MA, Phelan EM, Mandell MS, Conzen KD, Kelley SE, Nydam TL, Bak TE, Kam I, Wachs ME. Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy. World J Gastroenterol 2016; 22:3392-3403. [PMID: 27022221 PMCID: PMC4806197 DOI: 10.3748/wjg.v22.i12.3392] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Revised: 10/06/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate donation after circulatory death (DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy (HC) and patient/graft survival] and donor risk-conditions.
METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS DonorNet included preoperative systolic and diastolic blood pressure, heart rate, pH, SpO2, PaO2, FiO2, and hemoglobin. Mean arterial blood pressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O2 content was computed as [hemoglobin (gm/dL) × 1.37 (mL O2/gm) × SpO2%) + (0.003 × PaO2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure < 60 mmHg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry < 80% until clamping. Donor hypoxia score was (ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.
RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age (33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion (9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin (10.7 ± 2.2 gm/dL vs 12.3 ± 2.1 gm/dL, P = 0.017), lower preoperative arterial oxygen content (14.8 ± 2.8 mL O2/100 mL blood vs 16.8 ± 3.3 mL O2/100 mL blood, P = 0.049), greater hypoxia score >2.0 (69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure (92.7 ± 16.2 mmHg vs 83.8 ± 18.5 mmHg, P = 0.10). HC was independently associated with age, multi-pressor/red-cell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure (r2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2 (7.1/year)], compared to our early experience [era 1 (2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1 (P = 0.03). Era 2 donors had longer times for extubation-to-asystole (14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia (13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia (16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score > 2.0 rate (73.1% vs 28.6%, P = 0.006).
CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.
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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. Ann Surg 2016; 262:764-70; discussion 770-1. [PMID: 26583664 DOI: 10.1097/sla.0000000000001473] [Citation(s) in RCA: 284] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND 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. METHODS HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. RESULTS HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. CONCLUSIONS HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.
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Zhu XS, Wang SS, Cheng Q, Ye CW, Huo F, Li P. Using ultrasonography to monitor liver blood flow for liver transplant from donors supported on extracorporeal membrane oxygenation. Liver Transpl 2016; 22:188-91. [PMID: 26334555 DOI: 10.1002/lt.24318] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/12/2015] [Accepted: 08/20/2015] [Indexed: 01/13/2023]
Abstract
Extracorporeal membrane oxygenation (ECMO) has been used to support brain-dead donors for liver procurement. This study investigated the potential role of ultrasonographic monitoring of hepatic perfusion as an aid to improve the viability of liver transplants obtained from brain-dead donors who are supported on ECMO. A total of 40 brain-dead patients maintained on ECMO served as the study population. Hepatic blood flow was monitored using ultrasonography, and perioperative optimal perfusion was maintained by calibrating ECMO. Liver function tests were performed to assess the viability of the graft. The hepatic arterial blood flow was well maintained with no significant changes observed before and after ECMO (206 ± 32 versus 241 ± 45 mL/minute; P = 0.06). Similarly, the portal venous blood flow was also maintained throughout (451 ± 65 versus 482 ± 77 mL/minute; P = 0.09). No significant change in levels of total bilirubin, alanine transaminase, and lactic acid were reported during ECMO (P = 0.17, P = 0.08, and P = 0.09, respectively). Before the liver is procured, ultrasonographic monitoring of hepatic blood flow could be a valuable aid to improve the viability of a liver transplant by allowing for real-time calibration of ECMO perfusion in brain-dead liver donors. In our study, ultrasonographic monitoring helped prevent warm ischemic injury to the liver graft by avoiding both overperfusion and underperfusion of the liver.
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Affiliation(s)
- Xian-Sheng Zhu
- Department of Ultrasound, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
| | - Sha-Sha Wang
- Department of Ultrasound, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
| | - Qi Cheng
- Department of Ultrasound, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
| | - Chuang-Wen Ye
- Department of Ultrasound, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
| | - Feng Huo
- The Center for Liver Disease and Transplantation, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
| | - Peng Li
- The Center for Liver Disease and Transplantation, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangzhou, China
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Pezzati D, Ghinolfi D, De Simone P, Balzano E, Filipponi F. Strategies to optimize the use of marginal donors in liver transplantation. World J Hepatol 2015; 7:2636-47. [PMID: 26609341 PMCID: PMC4651908 DOI: 10.4254/wjh.v7.i26.2636] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 10/04/2015] [Accepted: 11/03/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD.
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Affiliation(s)
- Daniele Pezzati
- Daniele Pezzati, Davide Ghinolfi, Paolo De Simone, Emanuele Balzano, Franco Filipponi, Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Davide Ghinolfi
- Daniele Pezzati, Davide Ghinolfi, Paolo De Simone, Emanuele Balzano, Franco Filipponi, Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Paolo De Simone
- Daniele Pezzati, Davide Ghinolfi, Paolo De Simone, Emanuele Balzano, Franco Filipponi, Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Emanuele Balzano
- Daniele Pezzati, Davide Ghinolfi, Paolo De Simone, Emanuele Balzano, Franco Filipponi, Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
| | - Franco Filipponi
- Daniele Pezzati, Davide Ghinolfi, Paolo De Simone, Emanuele Balzano, Franco Filipponi, Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, 56124 Pisa, Italy
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O'Neill S, Roebuck A, Khoo E, Wigmore SJ, Harrison EM. A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation. Transpl Int 2015; 27:1159-74. [PMID: 25052036 DOI: 10.1111/tri.12403] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 05/05/2014] [Accepted: 07/12/2014] [Indexed: 12/11/2022]
Abstract
Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy (IC). This study aimed to compare outcomes between DCD and donation after brain death (DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify between-study predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers.
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Affiliation(s)
- Stephen O'Neill
- MRC Centre for Inflammation Research, Tissue Injury and Repair Group, University of Edinburgh, Edinburgh, UK
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Champigneulle B, Fieux F, Cheisson G, Dondero F, Savier E, Riou B, Langeron O, Nicolas-Robin A. French survey of the first three-years of liver transplantation activity from uncontrolled donors deceased after cardiac death. Anaesth Crit Care Pain Med 2015; 34:35-9. [PMID: 25829313 DOI: 10.1016/j.accpm.2014.05.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Accepted: 05/22/2014] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To assess the first three years of French activity related to liver transplantation from uncontrolled donation after cardiac death (uDCD). STUDY DESIGN Prospective and observational study in the three active centres authorized by the French Biomedicine Agency. PATIENTS AND METHODS All patients deceased between 2010 and 2012 after an uncontrolled cardiac arrest admitted to one of three centres (Pitié-Salpêtrière, Saint-Louis or Bicêtre hospitals, AP-HP, Paris, France) and potentially eligible for liver recovery were included. Abdominal normothermic oxygenated recirculation (ANOR) was used for graft preservation. RESULTS One hundred twenty-six potential uDCD donors were identified as eligible for liver recovery after hospital admission. The main causes of organ recovery failure were technical failure related to ANOR (29 patients, 23%), refusal of consent (39 patients, 31% of potential uDCD donors and 40% of asked relatives) and abnormal hepatic transaminases up to 200 UI.L(-1) during ANOR (24 patients, 19%). Finally, 11 livers were transplanted. Process efficiency was 9% [95% CI: 4-15%]. One-year recipient survival was 82%, [95% CI: 48-98%] and one-year graft survival was 64% [95% CI: 31-89%]. CONCLUSION Liver transplantation from uDCD donors is achievable in France, despite low process efficiency.
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Affiliation(s)
- B Champigneulle
- Department of Anesthesiology and Critical Care, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France
| | - F Fieux
- Department of Anesthesiology and Critical Care & Organ Transplant Coordination Team, hôpital Saint-Louis, AP-HP, Paris, France
| | - G Cheisson
- Department of Anesthesiology and Critical Care & Organ Transplant Coordination Team, hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France
| | - F Dondero
- Hepatobiliary Surgery and Liver Transplantation Department, hôpital Beaujon, AP-HP, Clichy, France
| | - E Savier
- Hepatobiliary Surgery and Liver Transplantation Department, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France
| | - B Riou
- Department of Emergency Medicine and Surgery, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France; UMRS Inserm 956, université médecine Pierre-et-Marie-Curie-Paris 6, 4, place Jussieu, 75005 Paris, France
| | - O Langeron
- Department of Anesthesiology and Critical Care, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France; UMRS Inserm 956, université médecine Pierre-et-Marie-Curie-Paris 6, 4, place Jussieu, 75005 Paris, France
| | - A Nicolas-Robin
- Department of Anesthesiology and Critical Care, groupe hospitalier Pitié-Salpêtrière, AP-HP, Paris, France; UMRS Inserm 956, université médecine Pierre-et-Marie-Curie-Paris 6, 4, place Jussieu, 75005 Paris, France.
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den Dulk AC, Sebib Korkmaz K, de Rooij BJF, Sutton ME, Braat AE, Inderson A, Dubbeld J, Verspaget HW, Porte RJ, van Hoek B. High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with donation after circulatory death. Transpl Int 2015; 28:492-501. [PMID: 25601020 DOI: 10.1111/tri.12524] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Revised: 09/21/2014] [Accepted: 01/11/2015] [Indexed: 12/11/2022]
Abstract
Orthotopic liver transplantation (OLT) with donation after circulatory death (DCD) often leads to a higher first week peak alanine aminotransferase (ALT) and a higher rate of biliary nonanastomotic strictures (NAS) as compared to donation after brain death (DBD). This retrospective study was to evaluate whether an association exists between peak ALT and the development of NAS in OLT with livers from DBD (n = 399) or DCD (n = 97) from two transplantation centers. Optimal cutoff value of peak ALT for risk of development of NAS post-DCD-OLT was 1300 IU/l. The 4-year cumulative incidence of NAS after DCD-OLT was 49.5% in patients with a high ALT peak post-OLT, compared with 11.3% in patients with a low ALT peak. (P < 0.001). No relation between peak ALT and NAS was observed after DBD-OLT. Multivariate analysis revealed peak ALT ≥1300 IU/l [adjusted hazard ratio (aHR) = 3.71, confidence interval (CI) (1.26-10.91)] and donor age [aHR = 1.04, CI 1.00-1.07] to be independently associated with development of NAS post-DCD-OLT. A peak ALT of <1300 IU/l carries a risk for NAS similar to DBD-OLT. Thus, in DCD-OLT, but not in DBD-OLT, peak ALT discriminates patients at high or low risk for NAS.
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Affiliation(s)
- A Claire den Dulk
- Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
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Bazerbachi F, Selzner N, Seal JB, Selzner M. Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge. World J Transl Med 2014; 3:58-68. [DOI: 10.5528/wjtm.v3.i2.58] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/11/2014] [Accepted: 07/17/2014] [Indexed: 02/05/2023] Open
Abstract
The scarcity of donor livers has increased the interest in donation after cardiac death (DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusion models, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.
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op den Dries S, Westerkamp AC, Karimian N, Gouw ASH, Bruinsma BG, Markmann JF, Lisman T, Yeh H, Uygun K, Martins PN, Porte RJ. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. J Hepatol 2014; 60:1172-9. [PMID: 24560661 DOI: 10.1016/j.jhep.2014.02.010] [Citation(s) in RCA: 146] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Revised: 01/19/2014] [Accepted: 02/04/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation. METHODS In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system. Histological severity of injury was subsequently compared in liver grafts that later developed biliary structures vs. uncomplicated liver grafts. RESULTS Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p<0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%, respectively; p=0.004). In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed NAS, compared to grafts without NAS (>50% vascular changes in 57.1% vs. 20.3%; p=0.006). CONCLUSION Injury of peribiliary glands and vascular plexus before transplantation is strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply may explain the development of biliary strictures.
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Affiliation(s)
- Sanna op den Dries
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Andrie C Westerkamp
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Negin Karimian
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Annette S H Gouw
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bote G Bruinsma
- Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA, United States
| | - James F Markmann
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Heidi Yeh
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Korkut Uygun
- Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, MA, United States
| | - Paulo N Martins
- Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Robert J Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
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Detry O, Deroover A, Meurisse N, Hans MF, Delwaide J, Lauwick S, Kaba A, Joris J, Meurisse M, Honoré P. Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme. Br J Surg 2014; 101:784-92. [PMID: 24771475 DOI: 10.1002/bjs.9488] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. METHODS All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. RESULTS A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). CONCLUSION Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized.
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Affiliation(s)
- O Detry
- Department of Abdominal Surgery and Transplantation, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium
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op den Dries S, Sutton ME, Karimian N, de Boer MT, Wiersema-Buist J, Gouw ASH, Leuvenink HGD, Lisman T, Porte RJ. Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PLoS One 2014; 9:e88521. [PMID: 24551114 PMCID: PMC3925142 DOI: 10.1371/journal.pone.0088521] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Accepted: 01/07/2014] [Indexed: 12/14/2022] Open
Abstract
Background Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model. Methods After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system. Results After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024). Conclusions Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.
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Affiliation(s)
- Sanna op den Dries
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Michael E. Sutton
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Negin Karimian
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marieke T. de Boer
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Janneke Wiersema-Buist
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Annette S. H. Gouw
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Henri G. D. Leuvenink
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J. Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- * E-mail:
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[Liver transplant with donated graft after controlled cardiac death. Current situation]. Cir Esp 2013; 91:554-62. [PMID: 24021972 DOI: 10.1016/j.ciresp.2013.04.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 04/04/2013] [Accepted: 04/08/2013] [Indexed: 02/07/2023]
Abstract
An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review.
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