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Zhang P, Liang H, Wang Y. Advances and Challenges of Thrombolytic Therapy for Donation After Circulatory Death Organs. Clin Transplant 2025; 39:e70099. [PMID: 39921605 DOI: 10.1111/ctr.70099] [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] [Received: 11/18/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 02/10/2025]
Abstract
The demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long-term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post-transplantation complications, most organs considered high-risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior-quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.
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Affiliation(s)
- Peng Zhang
- Department of General Surgery, Division of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, P.R. China
| | - Han Liang
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
| | - Yanfeng Wang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, Hubei, P.R. China
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Goto T, Noguchi Y, Linares I, Mazilescu L, Nogueira E, Hobeika C, Ray S, Parmentier C, Ganesh S, Peranantharuban J, Chan HH, Reichman T, Selzner N, Selzner M. Indocyanine green fluorescence quantification during normothermic ex situ perfusion for the assessment of porcine liver grafts after circulatory death. Liver Transpl 2024; 30:907-917. [PMID: 38869990 PMCID: PMC11332378 DOI: 10.1097/lvt.0000000000000416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 04/25/2024] [Indexed: 06/15/2024]
Abstract
Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.
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Affiliation(s)
- Toru Goto
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
- Department of Surgery, Divisions of Hepato-biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuki Noguchi
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Ivan Linares
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Laura Mazilescu
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Emmanuel Nogueira
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Christian Hobeika
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Samrat Ray
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Catherine Parmentier
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Sujani Ganesh
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Jathuya Peranantharuban
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Harley H.L. Chan
- TECHNA Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Trevor Reichman
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Nazia Selzner
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Markus Selzner
- Department of Surgery, Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Hessheimer AJ, Flores E, Vengohechea J, Fondevila C. Better liver transplant outcomes by donor interventions? Curr Opin Organ Transplant 2024; 29:219-227. [PMID: 38785132 DOI: 10.1097/mot.0000000000001153] [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: 05/25/2024]
Abstract
PURPOSE OF REVIEW Donor risk factors and events surrounding donation impact the quantity and quality of grafts generated to meet liver transplant waitlist demands. Donor interventions represent an opportunity to mitigate injury and risk factors within donors themselves. The purpose of this review is to describe issues to address among donation after brain death, donation after circulatory determination of death, and living donors directly, for the sake of optimizing relevant outcomes among donors and recipients. RECENT FINDINGS Studies on donor management practices and high-level evidence supporting specific interventions are scarce. Nonetheless, for donation after brain death (DBD), critical care principles are employed to correct cardiocirculatory compromise, impaired tissue oxygenation and perfusion, and neurohormonal deficits. As well, certain treatments as well as marginally prolonging duration of brain death among otherwise stable donors may help improve posttransplant outcomes. In donation after circulatory determination of death (DCD), interventions are performed to limit warm ischemia and reverse its adverse effects. Finally, dietary and exercise programs have improved donation outcomes for both standard as well as overweight living donor (LD) candidates, while minimally invasive surgical techniques may offer improved outcomes among LD themselves. SUMMARY Donor interventions represent means to improve liver transplant yield and outcomes of liver donors and grafts.
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Affiliation(s)
- Amelia J Hessheimer
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
| | - Eva Flores
- Transplant Coordination Unit, Hospital Universitario La Paz, Madrid, Spain
| | - Jordi Vengohechea
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
| | - Constantino Fondevila
- General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd
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Watson CJ, Gaurav R, Swift L, Fear C, Allison ME, Upponi SS, Brais R, Butler AJ. Bile Chemistry During Ex Situ Normothermic Liver Perfusion Does Not Always Predict Cholangiopathy. Transplantation 2024; 108:1383-1393. [PMID: 38409681 PMCID: PMC11115455 DOI: 10.1097/tp.0000000000004944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/20/2023] [Accepted: 01/08/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND Bile chemistry during normothermic ex situ liver perfusion (NESLiP) has been suggested to be an indicator of cholangiopathy. The normal range of biochemical variables in bile of livers undergoing NESLiP has not been defined, nor have published biliary viability criteria been assessed against instances of posttransplant nonanastomotic bile strictures (NASs). METHODS The bile and perfusate chemistry of 200 livers undergoing NESLiP between February 1, 2018, and October 30, 2023, was compared. In addition, 11 livers that underwent NESLiP and later developed NAS were selected and their bile chemistry was also examined. RESULTS In livers that did not develop cholangiopathy, concentrations of sodium, potassium, and chloride were slightly higher in bile than in perfusate, whereas the concentration of calcium was slightly lower. Bile was alkali and had a lower glucose concentration than perfusate. Cholangiocyte glucose reabsorption was shown to saturate at high perfusate concentrations and was more impaired in livers donated after circulatory death than in livers donated after brain death. Published criteria failed to identify all livers that went on to develop NASs. CONCLUSIONS A significant false-negative rate exists with current biliary viability criteria, probably reflecting the patchy and incomplete nature of the development of NASs in the biliary tree. The data presented here provide a benchmark for future assessment of bile duct chemistry during NESLiP.
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Affiliation(s)
- Christopher J.E. Watson
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- The National Institute of Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom
- The National Institute for Health Research Blood and Transplant Research Unit at the University of Cambridge in collaboration with Newcastle University and in partnership with National Health Service (NHS) Blood and Transplant, Cambridge, United Kingdom
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Rohit Gaurav
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Lisa Swift
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Corrina Fear
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Michael E.D. Allison
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
- Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Sara S. Upponi
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Rebecca Brais
- Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
- Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Andrew J. Butler
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- The National Institute of Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom
- The National Institute for Health Research Blood and Transplant Research Unit at the University of Cambridge in collaboration with Newcastle University and in partnership with National Health Service (NHS) Blood and Transplant, Cambridge, United Kingdom
- The Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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5
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Watson CJ, Gaurav R, Butler AJ. Current Techniques and Indications for Machine Perfusion and Regional Perfusion in Deceased Donor Liver Transplantation. J Clin Exp Hepatol 2024; 14:101309. [PMID: 38274508 PMCID: PMC10806097 DOI: 10.1016/j.jceh.2023.101309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/27/2023] [Indexed: 01/27/2024] Open
Abstract
Since the advent of University of Wisconsin preservation solution in the 1980s, clinicians have learned to work within its confines. While affording improved outcomes, considerable limitations still exist and contribute to the large number of livers that go unused each year, often for fear they may never work. The last 10 years have seen the widespread availability of new perfusion modalities which provide an opportunity for assessing organ viability and prolonged organ storage. This review will discuss the role of in situ normothermic regional perfusion for livers donated after circulatory death. It will also describe the different modalities of ex situ perfusion, both normothermic and hypothermic, and discuss how they are thought to work and the opportunities afforded by them.
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Affiliation(s)
- Christopher J.E. Watson
- University of Cambridge Department of Surgery, Box 210, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
| | - Rohit Gaurav
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
| | - Andrew J. Butler
- University of Cambridge Department of Surgery, Box 210, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
- The Roy Calne Transplant Unit, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK
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Al-Ameri AAM, Zhou Z, Zheng S. Comparative Analysis of Donor Liver Allograft Outcomes in Hepatocellular Carcinoma Patients Who Underwent Liver Transplant. EXP CLIN TRANSPLANT 2023; 21:664-670. [PMID: 37698401 DOI: 10.6002/ect.2023.0119] [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: 09/13/2023]
Abstract
OBJECTIVES Liver transplant for patients with hepatocellular carcinoma involves 3 main types of donor allografts: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Data on this topic are limited, and controversies exist regarding liver transplant outcomes in hepatocellular carcinoma patients who have received these allografts. MATERIALS AND METHODS Data from 490 hepatocellular carcinoma patients who received liver transplant from 2015 to 2021 at the Shulan (Hangzhou) Hospital were retrospectively analyzed. Participants were divided into 3 cohorts according to allograft type: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Kaplan-Meier and Cox regression methods were used to evaluate patient survival, graft survival, and recurrence-free survival rates after liver transplant. RESULTS Kaplan-Meier analysis revealed that 3-year patient survival rates were 69.2% for donations after brain death, 69.2% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .42); the 3-year graft survival rates were 53.3% for donations after brain death, 56.4% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .44); and 3-year recurrence-free survival rates were 55% for donations after brain death, 56.6% for donations after cardiac death, and 39.5% for donations after brain and cardiac death (P = .46). Complications were also similar across the 3 cohorts (P = .36). Multivariable analysis showed that intraoperative red blood cell transfusion (hazard ratio: 1.820; P = .042) and early allograft dysfunction (hazard ratio: 3.240; P = .041) were independent risk factors for graft survival. CONCLUSIONS Similar outcomes can be achieved for hepatocellular carcinoma patients who undergo liver transplant with donations after brain death, donations after cardiac death, or donations after brain and cardiac death allografts, especially when strict donor selection criteria are applied.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- >From the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; the Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China; and the NHC Key Laboratory of Combined Multi-organ Transplantation, the Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, and the Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou China
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Watson CJ, MacDonald S, Bridgeman C, Brais R, Upponi SS, Foukaneli T, Swift L, Fear C, Selves L, Kosmoliaptsis V, Allison M, Hogg R, Parsy KS, Thomas W, Gaurav R, Butler AJ. D-dimer Release From Livers During Ex Situ Normothermic Perfusion and After In Situ Normothermic Regional Perfusion: Evidence for Occult Fibrin Burden Associated With Adverse Transplant Outcomes and Cholangiopathy. Transplantation 2023; 107:1311-1321. [PMID: 36728501 PMCID: PMC10205116 DOI: 10.1097/tp.0000000000004475] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 10/10/2022] [Accepted: 10/29/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis. METHODS D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed. RESULTS Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture. CONCLUSIONS Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.
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Affiliation(s)
- Christopher J.E. Watson
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Stephen MacDonald
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Christopher Bridgeman
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Rebecca Brais
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Histopathology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Sara S. Upponi
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Radiology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Theodora Foukaneli
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Department of Haematology, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Lisa Swift
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Corrina Fear
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Linda Selves
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Michael Allison
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
- Department of Medicine, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
| | - Rachel Hogg
- Statistics and Clinical Research, NHS Blood and Transplant, Bristol, United Kingdom
| | - Kourosh Saeb Parsy
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Will Thomas
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- Specialist Haemostasis Laboratory, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Rohit Gaurav
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
| | - Andrew J. Butler
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom
- National Institute for Health and Care Research Blood and Transplant Research Unit in Organ Donation and Transplantation, at the University of Cambridge in collaboration with Newcastle University in partnership with National Health Service Blood and Transplant (NHSBT), Cambridge, United Kingdom
- Roy Calne Transplant Unit, Cambridge University Hospitals National Health Service Trust, Cambridge, United Kingdom
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8
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Ray S, Torres-Hernandez A, Bleszynski MS, Parmentier C, McGilvray I, Sayed BA, Shwaartz C, Cattral M, Ghanekar A, Sapisochin G, Tsien C, Selzner N, Lilly L, Bhat M, Jaeckel E, Selzner M, Reichman TW. Medical Assistance in Dying (MAiD) as a Source of Liver Grafts: Honouring the Ultimate Gift. Ann Surg 2023; 277:713-718. [PMID: 36515405 DOI: 10.1097/sla.0000000000005775] [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: 12/15/2022]
Abstract
OBJECTIVE To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.
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Affiliation(s)
- Samrat Ray
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
| | | | | | | | - Ian McGilvray
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Blayne Amir Sayed
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Chaya Shwaartz
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Mark Cattral
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Anand Ghanekar
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Cynthia Tsien
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Nazia Selzner
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Leslie Lilly
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Elmar Jaeckel
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Markus Selzner
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Trevor W Reichman
- Ajmera Transplant Centre, Toronto General Hospital, University Health Network
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
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9
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Hughes CB, Nigmet Y, Villanueva FS, Chen X, Demetris AJ, Stolz DB, Pacella JJ, Humar A. Ultrasound-Targeted Microbubble Cavitation During Machine Perfusion Reduces Microvascular Thrombi and Graft Injury in a Rat Liver Model of Donation After Circulatory Death. Transplant Proc 2023; 55:485-495. [PMID: 36878745 DOI: 10.1016/j.transproceed.2023.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/15/2023] [Accepted: 02/02/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Ischemic cholangiopathy is a process of bile duct injury that might result from peribiliary vascular plexus (PBP) thrombosis and remains a dreaded complication in liver transplantation from donors after circulatory death (DCD). The aim of this study was to propose a mechanical method of clot destruction to clear microvascular thrombi in DCD livers before transplantation. METHODS Sonothrombolysis (STL) is a process by which inertial cavitation of circulating microbubbles entering an ultrasound field create a high-energy shockwave at a microbubble-thrombus interface, causing mechanical clot destruction. The effectiveness of STL in DCD liver treatment remains unclear. We carried out STL treatment during normothermic, oxygenated, ex vivo machine perfusion (NMP), introducing microbubbles into the perfusate with the liver enveloped in an ultrasound field. RESULTS The STL livers showed reduction in hepatic arterial and PBP thrombus and decreases in hepatic arterial and portal venous flow resistance, reduced parenchymal injury as measured by aspartate transaminase release and oxygen consumption, and improved cholangiocyte function. Light and electron microscopy showed reduction of hepatic arterial and PBP thrombus in STL livers compared with controls and preserved hepatocyte structure, sinusoid endothelial morphology, and biliary epithelial microvilli. CONCLUSION In this model, STL improved flow and functional measures in DCD livers undergoing NMP. These data suggest a novel therapeutic approach to treat PBP injury in DCD livers, which may ultimately increase the pool of grafts available to patients awaiting liver transplantation.
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Affiliation(s)
- Christopher B Hughes
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
| | - Yermek Nigmet
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Flordeliza S Villanueva
- Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical, Pittsburgh, Pennsylvania
| | - Xucai Chen
- Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical, Pittsburgh, Pennsylvania
| | - Anthony J Demetris
- Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Donna B Stolz
- Center for Biological Imaging, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - John J Pacella
- Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical, Pittsburgh, Pennsylvania
| | - Abhinav Humar
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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10
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Krom RJ, Welsby IJ, Fuller M, Barbas AS, Gao Q, Anwar IJ, Dunkman WJ. Incidence of Postreperfusion Hyperfibrinolysis in Liver Transplantation by Donor Type and Observed Treatment Strategies. Anesth Analg 2023; 136:518-523. [PMID: 36729887 DOI: 10.1213/ane.0000000000006302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND Hyperfibrinolysis is a possible complication during liver transplantation, particularly immediately after reperfusion. METHODS We performed a retrospective study to examine the incidence, treatment, and resolution of postreperfusion hyperfibrinolysis in patients undergoing liver transplantation at Duke University Hospital from 2015 to 2020. RESULTS Out of 535 patients undergoing liver transplantation, 21 or 3.9%, 95% CI (2.5-5.9), had hyperfibrinolysis after reperfusion. Hyperfibrinolysis occurred in 16 of 511 (3.1%) patients receiving livers from DBD donors, 5 of 18 (27.8%) patients receiving livers from donation after circulatory death (DCD) donors, and 0 of 6 (0.0%) patients receiving livers from living donors. Fibrinolysis was treated with cryoprecipitate (12/21), a combination of cryoprecipitate and tranexamic acid (3/21), or neither (6/21) and resolved within several hours in all cases. CONCLUSIONS Anesthesiologists should be aware of the possibility of postreperfusion hyperfibrinolysis in liver transplantation, particularly with DCD donors, and may consider treatment with cryoprecipitate or tranexamic acid. Further work is needed to identify any potential differences, such as faster resolution of fibrinolysis, between different treatment modalities.
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Affiliation(s)
- Russell J Krom
- From the Department of Anesthesiology and Department of Surgery, Duke University Medical Center, Durham, North Carolina
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11
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Sellers MT, Nassar A, Alebrahim M, Sasaki K, Lee DD, Bohorquez H, Cannon RM, Selvaggi G, Neidlinger N, McMaster WG, Hoffman JRH, Shah AS, Montenovo MI. Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study. Clin Transplant 2022; 36:e14659. [PMID: 35362152 DOI: 10.1111/ctr.14659] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/07/2022] [Accepted: 03/25/2022] [Indexed: 11/28/2022]
Abstract
Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from 8 organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal pre-sepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; 1 patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Marty T Sellers
- Department of Surgery, Emory University, Atlanta, Georgia.,Tennessee Donor Services, Nashville, Tennessee
| | - Ahmed Nassar
- Department of Surgery, Emory University, Atlanta, Georgia
| | - Musab Alebrahim
- Department of Surgery, The Ohio State University, Columbus, Ohio
| | - Kazunari Sasaki
- Department of General Surgery, Cleveland Clinic, Cleveland, Ohio.,Department of Surgery, Stanford University
| | - David D Lee
- Department of Surgery, Loyola University, Chicago, Illinois
| | - Humberto Bohorquez
- Department of Surgery, Ochsner School of Medicine, New Orleans, Louisiana
| | - Robert M Cannon
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | | | | | - William G McMaster
- Department of Cardiac Surgery, Vanderbilt University, Nashville, Tennessee
| | - Jordan R H Hoffman
- Department of Cardiac Surgery, Vanderbilt University, Nashville, Tennessee
| | - Ashish S Shah
- Department of Cardiac Surgery, Vanderbilt University, Nashville, Tennessee
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12
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Wallace D, Cowling TE, Suddle A, Gimson A, Rowe I, Callaghan C, Sapisochin G, Ivanics T, Claasen M, Mehta N, Heaton N, van der Meulen J, Walker K. National time trends in mortality and graft survival following liver transplantation from circulatory death or brainstem death donors. Br J Surg 2021; 109:79-88. [PMID: 34738095 PMCID: PMC10364702 DOI: 10.1093/bjs/znab347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. METHODS Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008-2011 and 2012-2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. RESULTS A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142). CONCLUSION Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.
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Affiliation(s)
- David Wallace
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.,Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Thomas E Cowling
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
| | - Abid Suddle
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Alex Gimson
- The Liver Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Ian Rowe
- Liver Unit, St James' Hospital and University of Leeds, Leeds, UK/Leeds Institute for Data Analytics, University of Leeds, Leeds, UK
| | - Chris Callaghan
- Department of Nephrology and Transplantation, Renal Unit, Guy's Hospital, London, UK
| | - Gonzalo Sapisochin
- Multi-Organ Transplant, Toronto General Surgery, Toronto, Canada.,Department of General Surgery, University of Toronto, Toronto, Canada
| | - Tommy Ivanics
- Multi-Organ Transplant, Toronto General Surgery, Toronto, Canada.,Department of General Surgery, University of Toronto, Toronto, Canada
| | - Marco Claasen
- Multi-Organ Transplant, Toronto General Surgery, Toronto, Canada.,Department of General Surgery, University of Toronto, Toronto, Canada
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Jan van der Meulen
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
| | - Kate Walker
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
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13
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Crannell WC, Sally M, McConnell K, Connelly C, Maynard E, Dewey E, Abt P, Enestvedt CK. Thromboelastography profiles for controlled circulatory death donors: Validating the role of heparin. Clin Transplant 2021; 36:e14518. [PMID: 34668240 DOI: 10.1111/ctr.14518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 09/23/2021] [Accepted: 09/23/2021] [Indexed: 11/29/2022]
Abstract
Controlled donation after circulatory death (cDCD) liver transplants are associated with increased ischemic-type biliary complications. Microvascular thrombosis secondary to decreased donor fibrinolysis may contribute to bile duct injury. We hypothesized that cDCD donors are hypercoagulable with impaired fibrinolysis and aim to use thromboelastography to characterize cDCD coagulation profiles.
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Affiliation(s)
- W Christian Crannell
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - Mitch Sally
- Department of Surgery, Division of Trauma, Critical Care, and Acute Care Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Keeley McConnell
- Department of Surgery, Division of Trauma, Critical Care, and Acute Care Surgery, Oregon Health & Science University, Portland, Oregon, USA
| | - Chris Connelly
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - Erin Maynard
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - Elizabeth Dewey
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - Peter Abt
- Department of Surgery, Division of Transplantation, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - C Kristian Enestvedt
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
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14
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Regulations and Procurement Surgery in DCD Liver Transplantation: Expert Consensus Guidance From the International Liver Transplantation Society. Transplantation 2021; 105:945-951. [PMID: 33675315 DOI: 10.1097/tp.0000000000003729] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Donation after circulatory death (DCD) donors are an increasingly more common source of livers for transplantation in many parts of the world. Events that occur during DCD liver recovery have a significant impact on the success of subsequent transplantation. This working group of the International Liver Transplantation Society evaluated current evidence as well as combined experience and created this guidance on DCD liver procurement. Best practices for the recovery and transplantation of livers arising through DCD after euthanasia and organ procurement with super-rapid cold preservation and recovery as well as postmortem normothermic regional perfusion are described, as are the use of adjuncts during DCD liver procurement.
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15
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Early Allograft Dysfunction After Liver Transplantation With Donation After Circulatory Death and Brain Death Grafts: Does the Donor Type Matter? Transplant Direct 2021; 7:e727. [PMID: 34291149 PMCID: PMC8288897 DOI: 10.1097/txd.0000000000001182] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/04/2021] [Accepted: 04/29/2021] [Indexed: 11/30/2022] Open
Abstract
Background. Early allograft dysfunction (EAD) after liver transplantation has been associated with long-term reduced graft and patient survival. Methods. In this single-center cohort study, we aimed to compare incidence, risk factors, and outcomes in liver transplant recipients who developed EAD. Patients who received donation after circulatory death (DCD) or donation after brain death (DBD) grafts between January 2007 and December 2017 were included. EAD was defined as bilirubin of ≥10 mg/dL (171 μmol/L) or an international normalized ratio of ≥1.6 on postoperative day 7 or transaminases >2000 U\L in the first-week posttransplantation as previously described. Results. In our cohort of 1068 patients, incidence of EAD was 44%. EAD occurred more frequently in the DCD versus DBD group (71% versus 41%, P < 0.01). Overall, recipients who developed EAD showed a significantly lower graft and patient survival at 1, 3, and 5 y after transplantation (all P < 0.05). This was also the case for recipients of DBD grafts. However, for recipients of DCD grafts, patient and graft survival were not affected by the presence of EAD. For recipients of DBD grafts, donor age, body mass index (BMI) and gender, recipient BMI and model for end-stage liver disease score and warm and cold ischemia time were associated with EAD. For DCD recipients, donor BMI and cold ischemia time were associated with EAD. Conclusions. In our cohort study, EAD resulted in reduced long-term patient and graft survival only for DBD recipients but not for DCD recipients. Predictive markers for EAD were dependent on the donor type.
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16
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Haque O, Raigani S, Rosales I, Carroll C, Coe TM, Baptista S, Yeh H, Uygun K, Delmonico FL, Markmann JF. Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury. Front Surg 2021; 8:644859. [PMID: 34222314 PMCID: PMC8245781 DOI: 10.3389/fsurg.2021.644859] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 05/24/2021] [Indexed: 12/29/2022] Open
Abstract
Background: A major limitation in expanding the use of donation after circulatory death (DCD) livers in transplantation is the increased risk of graft failure secondary to ischemic cholangiopathy. Warm ischemia causes thrombosis and injury to the peribiliary vascular plexus (PVP), which is supplied by branches of the hepatic artery, causing higher rates of biliary complications in DCD allografts. Aims/Objectives: We aimed to recondition discarded DCD livers with tissue plasminogen activator (tPA) while on normothermic machine perfusion (NMP) to improve PVP blood flow and reduce biliary injury. Methods: Five discarded DCD human livers underwent 12 h of NMP. Plasminogen was circulated in the base perfusate prior to initiation of perfusion and 1 mg/kg of tPA was administered through the hepatic artery at T = 0.5 h. Two livers were split prior to perfusion (S1, S2), with tPA administered in one lobe, while the other served as a control. The remaining three whole livers (W1-W3) were compared to seven DCD control liver perfusions (C1-C7) with similar hepatocellular and biliary viability criteria. D-dimer levels were measured at T = 1 h to verify efficacy of tPA. Lactate, total bile production, bile pH, and difference in biliary injury scores before and after perfusion were compared between tPA and non-tPA groups using unpaired, Mann-Whitney tests. Results: Average weight-adjusted D-dimer levels were higher in tPA livers in the split and whole-liver model, verifying drug function. There were no differences in perfusion hepatic artery resistance, portal vein resistance, and arterial lactate between tPA livers and non-tPA livers in both the split and whole-liver model. However, when comparing biliary injury between hepatocellular and biliary non-viable whole livers, tPA livers had significantly lower PVP injury scores (0.67 vs. 2.0) and mural stroma (MS) injury scores (1.3 vs. 2.7). Conclusion: This study demonstrates that administration of tPA into DCD livers during NMP can reduce PVP and MS injury. Further studies are necessary to assess the effect of tPA administration on long term biliary complications.
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Affiliation(s)
- Omar Haque
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Siavash Raigani
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Ivy Rosales
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Cailah Carroll
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Taylor M Coe
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Sofia Baptista
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Heidi Yeh
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Korkut Uygun
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Francis L Delmonico
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States.,New England Donor Services (NEDS), Waltham, MA, United States
| | - James F Markmann
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
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17
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Kalisvaart M, Croome KP, Hernandez-Alejandro R, Pirenne J, Cortés-Cerisuelo M, Miñambres E, Abt PL. Donor Warm Ischemia Time in DCD Liver Transplantation-Working Group Report From the ILTS DCD, Liver Preservation, and Machine Perfusion Consensus Conference. Transplantation 2021; 105:1156-1164. [PMID: 34048418 DOI: 10.1097/tp.0000000000003819] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation.
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Affiliation(s)
- Marit Kalisvaart
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | | | | | - Jacques Pirenne
- Department of Abdominal Transplant Surgery, University Hospital Leuven, Leuven, Belgium
| | - Miriam Cortés-Cerisuelo
- Department of Liver Transplantation, Institute of Liver Studies, King's College Hospital NHS Trust, London, United Kingdom
| | - Eduardo Miñambres
- Transplant Coordination Unit and Service of Intensive Care, University Hospital Marqués de Valdecilla-IDIVAL, School of Medicine, University of Cantabria, Santander, Spain
| | - Peter L Abt
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
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18
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Haque O, Yuan Q, Uygun K, Markmann JF. Evolving utilization of donation after circulatory death livers in liver transplantation: The day of DCD has come. Clin Transplant 2021; 35:e14211. [PMID: 33368701 PMCID: PMC7969458 DOI: 10.1111/ctr.14211] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 11/29/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022]
Abstract
Compared to donation after brain death (DBD), livers procured for transplantation from donation after circulatory death (DCD) donors experience more ischemia-reperfusion injury and higher rates of ischemic cholangiopathy due to the period of warm ischemic time (WIT) following withdrawal of life support. As a result, utilization of DCD livers for liver transplant (LT) has generally been limited to short WITs and younger aged donor grafts, causing many recovered DCD organs to be discarded without consideration for transplant. This study assesses how DCD liver utilization and outcomes have changed over time, using OPTN data from adult, first-time, deceased donor, whole-organ LTs between January 1995 and December 2019. Results show that increased clinical experience with DCD LT has translated into increased use of livers from DCD donors, shorter ischemic times, shorter lengths of hospitalization after transplant, and lower rates of retransplantation. The data also reveal that over the past decade, the rate of increase in DCD LTs conducted in the United States has outpaced that of DBD. Together, these trends signal an opportunity for the field of liver transplantation to mitigate the organ shortage by capitalizing on DCD liver allografts that are currently not being utilized.
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Affiliation(s)
- Omar Haque
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, MA, USA
- Shriners Hospitals for Children, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Qing Yuan
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- 8th Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Korkut Uygun
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, MA, USA
- Shriners Hospitals for Children, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - James F Markmann
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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19
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Kubal C, Roll GR, Ekser B, Muiesan P. Donation after circulatory death liver transplantation: What are the limits for an acceptable DCD graft? Int J Surg 2020; 82S:36-43. [PMID: 32389812 DOI: 10.1016/j.ijsu.2020.04.064] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/17/2020] [Accepted: 04/27/2020] [Indexed: 01/06/2023]
Abstract
The utilization of donation after circulatory death (DCD) livers has been growing over the last decade. In large-volume centers, survival outcomes have improved and are comparable to outcomes with brain death donor (DBD) liver transplantation (LT). The relatively concentrated success with DCD LT demonstrated by high-volume transplant centers has rekindled international enthusiasm. The combination of increasing expertise in DCD LT and ongoing shortage in transplantable organs has promoted expansion of the DCD donor pool with regards to donor age, body mass index and donor warm ischemia time. In this review, we focused on the practice patterns in DCD liver graft utilization in the last decade, along with the possibilities for further expansion of DCD liver graft utilization and new technologies, such as machine perfusion.
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Affiliation(s)
- ChandrashekharA Kubal
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Garrett R Roll
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, CA, USA.
| | - Burcin Ekser
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Paolo Muiesan
- The Liver Unit, Queen Elizabeth University Hospital, Birmingham, United Kingdom.
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20
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Karangwa SA, Lisman T, Porte RJ. Anticoagulant Management and Synthesis of Hemostatic Proteins during Machine Preservation of Livers for Transplantation. Semin Thromb Hemost 2020; 46:743-750. [DOI: 10.1055/s-0040-1715452] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AbstractLiver transplantation remains the only curative treatment for patients with end-stage liver disease. Despite a steadily increasing demand for suitable donor livers, the current pool of donor organs fails to meet this demand. To resolve this discrepancy, livers traditionally considered to be of suboptimal quality and function are increasingly utilized. These marginal livers, however, are less tolerant to the current standard cold preservation of donor organs. Therefore, alternative preservation methods have been sought and are progressively applied into clinical practice. Ex situ machine perfusion is a promising alternative preservation modality particularly for suboptimal donor livers as it provides the ability to resuscitate, recondition, and test the viability of an organ prior to transplantation. This review addresses the modalities of machine perfusion currently being applied, and particularly focuses on the hemostatic management employed during machine perfusion. We discuss the anticoagulant agents used, the variation in dosage, and administration, as well as the implications of perfusion for extended periods of time in terms of coagulation activation associated with production of coagulation factors during perfusion. Furthermore, in regard to viability testing of an organ prior to transplantation, we discuss the possibilities and limitations of utilizing the synthesis of liver-derived coagulation factors as potential viability markers.
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Affiliation(s)
- Shanice A. Karangwa
- Department of Surgery, Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Department of Surgery, Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J. Porte
- Section of HPB Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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21
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Nagai S, Chau LC, Kitajima T, Yeddula S, Collins K, Rizzari M, Yoshida A, Abouljoud MS, Moonka D. A Share 21 model in liver transplantation: Impact on waitlist outcomes. Am J Transplant 2020; 20:2184-2197. [PMID: 32155314 DOI: 10.1111/ajt.15836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/09/2020] [Accepted: 02/04/2020] [Indexed: 01/25/2023]
Abstract
With the introduction of Model for End-Stage Liver Disease-Sodium (MELD-Na)-based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD-Na scores <21 and explore the utility of replacing "Share 15" with "Share 21." The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD-Na-based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD-Na score of 6-14 (Group 1) and those with a score of 15-20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6-14 (Group 1) and 3282 with a score of 15-20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD-Na scores without compromising waitlist outcomes.
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Affiliation(s)
- Shunji Nagai
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Lucy C Chau
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Toshihiro Kitajima
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Sirisha Yeddula
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Kelly Collins
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Michael Rizzari
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Atsushi Yoshida
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Marwan S Abouljoud
- Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, Michigan
| | - Dilip Moonka
- Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan
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22
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Croome KP. Donation after Circulatory Death: Potential Mechanisms of Injury and Preventative Strategies. Semin Liver Dis 2020; 40:256-263. [PMID: 32557479 DOI: 10.1055/s-0040-1709487] [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] [Indexed: 02/01/2023]
Abstract
Donation after circulatory death (DCD) donors represent a potential means to help address the disparity between the number of patients awaiting liver transplantation (LT) and the availability of donor livers. While initial enthusiasm for DCD LT was high in the early 2000s, early reports of high rates of biliary complications and inferior graft survival resulted in reluctance among many transplant centers to use DCD liver grafts. As with all innovations in transplant practice, there is undoubtedly a learning curve associated with the optimal utilization of liver grafts from DCD donors. More contemporary data has demonstrated that results with DCD LT are improving and the number of DCD LT performed annually has been steadily increasing. In this concise review, potential mechanisms of injury for DCD livers are discussed along with strategies that have been employed in clinical practice to improve DCD LT outcomes.
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23
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Hessheimer AJ, Gastaca M, Miñambres E, Colmenero J, Fondevila C. Donation after circulatory death liver transplantation: consensus statements from the Spanish Liver Transplantation Society. Transpl Int 2020; 33:902-916. [PMID: 32311806 PMCID: PMC7496958 DOI: 10.1111/tri.13619] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 02/06/2020] [Accepted: 04/14/2020] [Indexed: 02/06/2023]
Abstract
Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.
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Affiliation(s)
- Amelia J. Hessheimer
- Liver Transplant UnitCIBERehdIDIBAPSHospital ClínicUniversity of BarcelonaBarcelonaSpain
| | - Mikel Gastaca
- Hospital Universitario CrucesBilbaoSpain
- SETH Board of DirectorsSpain
| | - Eduardo Miñambres
- Transplant Coordination Unit & Intensive Care ServiceIDIVALHospital Universitario Marqués de ValdecillaUniversity of CantabriaSantanderSpain
| | - Jordi Colmenero
- Liver Transplant UnitCIBERehdIDIBAPSHospital ClínicUniversity of BarcelonaBarcelonaSpain
- SETH Board of DirectorsSpain
| | - Constantino Fondevila
- Liver Transplant UnitCIBERehdIDIBAPSHospital ClínicUniversity of BarcelonaBarcelonaSpain
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24
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Hashimoto K. Liver graft from donation after circulatory death donor: Real practice to improve graft viability. Clin Mol Hepatol 2020; 26:401-410. [PMID: 32646199 PMCID: PMC7641554 DOI: 10.3350/cmh.2020.0072] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 05/27/2020] [Indexed: 12/14/2022] Open
Abstract
Donation after circulatory death (DCD) is an increasing source of liver grafts for transplantation, yet outcomes have been inferior compared to donation after brain death liver transplantation. These worse outcomes are mainly due to the severe graft injury resulting from mandatory warm ischemia during DCD organ recovery. New evidence, however, indicates that improved donor selection and surgical techniques can decrease the risk of graft failure and ischemic cholangiopathy (IC). Under current best practices, DCD organs are retrieved with the super-rapid technique, optimizing timing and protecting the liver graft from detrimental warm ischemia. Graft viability is influenced by both the quantity and quality of warm ischemia, which is unique to each donor and causes various degrees of pathophysiologic consequences. Evidence also shows that the choice of preservation solution and premortem heparin administration influences graft viability. Additionally, although the precise mechanism of IC remains unknown, stasis of blood during donor warm ischemia may cause the formation of microthrombi in the peribiliary vascular plexus and ischemia of the bile duct. Importantly, thrombolytic protocols show a possible preventive modality for IC. Finally, while ex vivo machine perfusion technology has gained an interest in DCD liver transplantation, further studies are necessary to evaluate the effectiveness of this evolving field to improve graft quality and transplant outcomes.
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Affiliation(s)
- Koji Hashimoto
- Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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25
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DiRito JR, Hosgood SA, Reschke M, Albert C, Bracaglia LG, Ferdinand JR, Stewart BJ, Edwards CM, Vaish AG, Thiru S, Mulligan DC, Haakinson DJ, Clatworthy MR, Saltzman WM, Pober JS, Nicholson ML, Tietjen GT. Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys. Am J Transplant 2020; 21:161-173. [PMID: 32627324 PMCID: PMC7775334 DOI: 10.1111/ajt.16148] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/15/2020] [Accepted: 06/08/2020] [Indexed: 01/25/2023]
Abstract
Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs. In a recent study of 8 transplant-declined human kidneys on NMP, we discovered microvascular obstructions that impaired microvascular blood flow. However, the nature and physiologic impact of these lesions were unknown. Here, in a study of 39 human kidneys, we have identified that prolonged cold storage of human kidneys induces accumulation of fibrinogen within tubular epithelium. Restoration of normoxic conditions-either ex vivo during NMP or in vivo following transplant-triggered intravascular release of fibrinogen correlating with red blood cell aggregation and microvascular plugging. Combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs leading to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular-targeted nanoparticles. Our study suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential.
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Affiliation(s)
- Jenna R. DiRito
- Department of Surgery, University of Cambridge, Cambridge, UK,Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | | | - Melanie Reschke
- Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut
| | - Claire Albert
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | - Laura G. Bracaglia
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | - John R. Ferdinand
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
| | - Benjamin J. Stewart
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Anand G. Vaish
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | - Sathia Thiru
- Department of Pathology, University of Cambridge, Cambridge, UK
| | - David C. Mulligan
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | | | - Menna R. Clatworthy
- Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
| | - W. Mark Saltzman
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | - Jordan S. Pober
- Department of Immunobiology, Yale University, New Haven, Connecticut
| | | | - Gregory T. Tietjen
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut,Department of Biomedical Engineering, Yale University, New Haven, Connecticut
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26
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Pérez IB, Duca A. Top Papers in Liver Transplantation 2017-2018. Transplant Proc 2020; 53:620-623. [PMID: 32247594 DOI: 10.1016/j.transproceed.2020.01.085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 01/10/2020] [Indexed: 12/14/2022]
Abstract
Organ shortage remains a major limitation in liver transplantation, and there has been a significant effort over the past decade to increase the existing deceased donor pool. Recent advances have included better selection and management of donors after circulatory arrest, application of hypothermic and normothermic perfusion, minimization of standard immunosuppression, and use of new immunosuppressive medications. Additionally, there has been renewed emphasis and understanding of liver immunology and the impact of antibody-mediated rejection. Together, these advances have allowed for expansion of the donor pool with concurrent improved patient outcomes. Furthermore, direct-acting antiviral agents for the treatment of hepatitis C virus infection has been management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. In this article, we analyze some of the top papers published in 2017-2018 dealing with these issues.
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Affiliation(s)
- Isolina Baños Pérez
- Unit Transplantation Liver, Internal Medicine Service, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
| | - Ana Duca
- Unit Transplantation Liver, Internal Medicine Service, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
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27
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Nostedt JJ, Shapiro J, Freed DH, Bigam DL. Addressing organ shortages: progress in donation after circulatory death for liver transplantation. Can J Surg 2020; 63:E135-E141. [PMID: 32195556 DOI: 10.1503/cjs.005519] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Reducing wait list mortality among patients awaiting liver transplantation remains a substantial challenge because of organ shortage. In efforts to expand the donor pool there has been a trend toward increased use of donation after circulatory death (DCD) liver grafts. However, these marginal grafts are prone to higher complication rates, particularly biliary complications. In addition, many procured DCD livers are then deemed unsuitable for transplant. Despite these limitations, DCD grafts represent an important resource to address the current organ shortage, and as such there are research efforts directed toward improving the use of and outcomes for transplantation of these grafts. We review the current progress in DCD liver transplantation.
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Affiliation(s)
- Jordan J. Nostedt
- From the Department of Surgery, Division of General Surgery, University of Alberta Hospital, Edmonton, Alta. (Nostedt, Shapiro, Bigam); the Department of Physiology, University of Alberta, Edmonton, Alta. (Freed); and the Department of Surgery, Division of Cardiac Surgery, University of Alberta, Alberta Heart Institute, Edmonton, Alta. (Freed)
| | - James Shapiro
- From the Department of Surgery, Division of General Surgery, University of Alberta Hospital, Edmonton, Alta. (Nostedt, Shapiro, Bigam); the Department of Physiology, University of Alberta, Edmonton, Alta. (Freed); and the Department of Surgery, Division of Cardiac Surgery, University of Alberta, Alberta Heart Institute, Edmonton, Alta. (Freed)
| | - Darren H. Freed
- From the Department of Surgery, Division of General Surgery, University of Alberta Hospital, Edmonton, Alta. (Nostedt, Shapiro, Bigam); the Department of Physiology, University of Alberta, Edmonton, Alta. (Freed); and the Department of Surgery, Division of Cardiac Surgery, University of Alberta, Alberta Heart Institute, Edmonton, Alta. (Freed)
| | - David L. Bigam
- From the Department of Surgery, Division of General Surgery, University of Alberta Hospital, Edmonton, Alta. (Nostedt, Shapiro, Bigam); the Department of Physiology, University of Alberta, Edmonton, Alta. (Freed); and the Department of Surgery, Division of Cardiac Surgery, University of Alberta, Alberta Heart Institute, Edmonton, Alta. (Freed)
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28
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Favorable Outcomes After Liver Transplantation With Normothermic Regional Perfusion From Donors After Circulatory Death: A Single-center Experience. Transplantation 2019; 103:938-943. [PMID: 30063694 DOI: 10.1097/tp.0000000000002391] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Controlled donation after circulatory death (cDCD) has been associated with a high incidence of ischemic cholangiopathy and other perioperative complications. In an attempt to avoid these complications, we implemented an active protocol of cDCD liver transplant (LT) with normothermic regional perfusion (NRP) preservation. METHODS This is a descriptive analysis of data collected from a prospective date base of cDCD LT preserved with NRP from January 2015 to June 2017 with a minimum follow up of 9 months. RESULTS Fifty-seven potential cDCD donors were connected to the NRP system. Of these, 46 livers were transplanted over a 30-month period (80% liver recovery rate). The median posttransplant peak in alanine transaminase was 1136 U/L (220-6683 U/L). Seven (15%) patients presented postreperfusion syndrome and 11 (23%) showed early allograft dysfunction. No cases of ischemic cholangiopathy were diagnosed, and no graft loss was observed over a medium follow-up period of 19 months. Of note, 13 donors were older than 65 years, achieving comparable perioperative and midterm results to younger donors. CONCLUSIONS As far as we know, this represents the largest published series of cDCD LT with NRP preservation. Our results demonstrate that cDCD liver grafts preserved with NRP appear far superior to those obtained by the conventional rapid recovery technique.
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29
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Tun-Abraham ME, Wanis K, Garcia-Ochoa C, Sela N, Sharma H, Al Hasan I, Quan D, Al-Judaibi B, Levstik M, Hernandez-Alejandro R. Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience. Can J Surg 2019. [PMID: 30484989 DOI: 10.1503/cjs.012017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. Methods We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Results Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era. Conclusion We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.
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Affiliation(s)
- Mauro Enrique Tun-Abraham
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Kerollos Wanis
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Carlos Garcia-Ochoa
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Nathalie Sela
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Hemant Sharma
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Ibrahim Al Hasan
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Douglas Quan
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Bandar Al-Judaibi
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Mark Levstik
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Roberto Hernandez-Alejandro
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
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30
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Paterno F, Guarrera JV, Wima K, Diwan T, Cuffy MC, Anwar N, Woodle ES, Shah S. Clinical Implications of Donor Warm and Cold Ischemia Time in Donor After Circulatory Death Liver Transplantation. Liver Transpl 2019; 25:1342-1352. [PMID: 30912253 DOI: 10.1002/lt.25453] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 03/19/2019] [Indexed: 02/07/2023]
Abstract
The use of donation after circulatory death (DCD) liver allografts has been constrained by limitations in the duration of donor warm ischemia time (DWIT), donor agonal time (DAT), and cold ischemia time (CIT). The purpose of this study is to assess the impact of longer DWIT, DAT, and CIT on graft survival and other outcomes in DCD liver transplants. The Scientific Registry of Transplant Recipients was queried for adult liver transplants from DCD donors between 2009 and 2015. Donor, recipient, and center variables were included in the analysis. During the study period, 2107 patients underwent liver transplant with DCD allografts. In most patients, DWIT and DAT were <30 minutes. DWIT was <30 minutes in 1804 donors, between 30 and 40 minutes in 248, and >40 minutes in 37. There was no difference in graft survival, duration of posttransplant hospital length of stay, and readmission rate between DCD liver transplants from donors with DWIT <30 minutes and DWIT between 30 and 40 minutes. Similar outcomes were noted for DAT. In the multivariate analysis, DAT and DWIT were not associated with graft loss. The predictors associated with graft loss were donor age, donor sharing, CIT, recipient admission to the intensive care unit, recipient ventilator dependence, Model for End-Stage Liver Disease score, and low-volume transplant centers. Any CIT cutoff >4 hours was associated with increased risk for graft loss. Longer CIT was also associated with a longer posttransplant hospital stay, higher rate of primary nonfunction, and hyperbilirubinemia. In conclusion, slightly longer DAT and DWIT (up to 40 minutes) were not associated with graft loss, longer posttransplant hospitalization, or hospital readmissions, whereas longer CIT was associated with worse outcomes after DCD liver transplants.
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Affiliation(s)
- Flavio Paterno
- Division of Liver Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School and University Hospital, Newark, NJ
| | - James V Guarrera
- Division of Liver Transplant and Hepatobiliary Surgery, Department of Surgery, Rutgers New Jersey Medical School and University Hospital, Newark, NJ
| | - Koffi Wima
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Tayyab Diwan
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Madison C Cuffy
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Nadeem Anwar
- Division of Hepatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
| | - E Steve Woodle
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Shimul Shah
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH
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31
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Mihaylov P, Mangus R, Ekser B, Cabrales A, Timsina L, Fridell J, Lacerda M, Ghabril M, Nephew L, Chalasani N, Kubal CA. Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers. Liver Transpl 2019; 25:1198-1208. [PMID: 30929303 DOI: 10.1002/lt.25462] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 03/16/2019] [Indexed: 02/07/2023]
Abstract
Use of donation after circulatory death (DCD) donor livers for transplantation has remained cautious in the United States. The aim of this study was to demonstrate the expansion of a DCD liver transplantation (LT) program with the use of extended criteria donor (ECD) DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with 1 of the following factors: donor age >50 years, donor body mass index >35 kg/m2 , donor functional warm ischemia time >30 minutes, and donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush and efforts to minimize ischemia times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC), and change in DCD LT volume. Of 135 consecutive DCD LTs, 62 were ECD DCDs. In total, 24 ECD DCD LTs were performed before (era 1) and 38 after the institution of optimization protocol (era 2), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in era 2, with a significantly lower incidence of IC (5% versus 17% in era 1; P = 0.03) and better 1-year graft survival (93% versus 75% in era 1; P = 0.07). Survival outcomes for ECD DCD LT in era 2 were comparable to matched deceased donor LT. With the expansion of the DCD donor pool, the number of DCD LTs performed at our center gradually increased in era 2 to account for >20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.
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Affiliation(s)
- Plamen Mihaylov
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Richard Mangus
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Burcin Ekser
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Arianna Cabrales
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Lava Timsina
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Jonathan Fridell
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Marco Lacerda
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
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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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Hessheimer AJ, Coll E, Torres F, Ruíz P, Gastaca M, Rivas JI, Gómez M, Sánchez B, Santoyo J, Ramírez P, Parrilla P, Marín LM, Gómez-Bravo MÁ, García-Valdecasas JC, López-Monclús J, Boscá A, López-Andújar R, Fundora-Suárez J, Villar J, García-Sesma Á, Jiménez C, Rodríguez-Laíz G, Lladó L, Rodríguez JC, Barrera M, Charco R, López-Baena JÁ, Briceño J, Pardo F, Blanco G, Pacheco D, Domínguez-Gil B, Sánchez Turrión V, Fondevila C. Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation. J Hepatol 2019; 70:658-665. [PMID: 30582980 DOI: 10.1016/j.jhep.2018.12.013] [Citation(s) in RCA: 214] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 11/14/2018] [Accepted: 12/08/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD. METHODS This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes. RESULTS During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45-65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06-0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02-0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20-0.78; p = 0.008). CONCLUSIONS The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age. LAY SUMMARY This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.
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Affiliation(s)
- Amelia J Hessheimer
- Department of General & Digestive Surgery, Institut de Malalties Digestives i Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Ferrán Torres
- Medical Statistics Core Facility, IDIBAPS, Hospital Clínic Barcelona & Biostatistics Unit, Faculty of Medicine, Universidad Autónoma de Barcelona, Barcelona, Spain
| | | | | | | | - Manuel Gómez
- Complejo Hospitalario Universitario La Coruña, La Coruña, Spain
| | | | - Julio Santoyo
- Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Pablo Ramírez
- Hospital Clínico Universitario Virgen de la Arrixaca (IMIB), Murcia, Spain
| | - Pascual Parrilla
- Hospital Clínico Universitario Virgen de la Arrixaca (IMIB), Murcia, Spain
| | | | | | - Juan Carlos García-Valdecasas
- Department of General & Digestive Surgery, Institut de Malalties Digestives i Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Andrea Boscá
- Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | | | | | - Jesús Villar
- Hospital Universitario Virgen de las Nieves, Granada, Spain
| | | | | | - Gonzalo Rodríguez-Laíz
- Department of General & Digestive Surgery, ISABIAL, Hospital General Universitario de Alicante, Alicante, Spain
| | - Laura Lladó
- Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain
| | | | - Manuel Barrera
- Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Ramón Charco
- Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | | | | | | | | | - David Pacheco
- Hospital Universitario Río Hortega, Valladolid, Spain
| | | | | | - Constantino Fondevila
- Department of General & Digestive Surgery, Institut de Malalties Digestives i Metabòliques (IMDiM), Hospital Clínic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain.
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Tchilikidi KY. Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion. World J Gastrointest Surg 2019; 11:126-142. [PMID: 31057698 PMCID: PMC6478595 DOI: 10.4240/wjgs.v11.i3.126] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/21/2019] [Accepted: 03/24/2019] [Indexed: 02/06/2023] Open
Abstract
The growing demand for donor organs requires measures to expand donor pool. Those include extended criteria donors, such as elderly people, steatotic livers, donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion (NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury. Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose. Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.
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Tun-Abraham ME, Wanis K, Garcia-Ochoa C, Sela N, Sharma H, Al Hasan I, Quan D, Al-Judaibi B, Levstik M, Hernandez-Alejandro R. Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience. CANADIAN JOURNAL OF SURGERY. JOURNAL CANADIEN DE CHIRURGIE 2019; 62:44-51. [PMID: 30484989 DOI: 10.503/cjs.012017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. Methods We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Results Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era. Conclusion We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.
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Affiliation(s)
- Mauro Enrique Tun-Abraham
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Kerollos Wanis
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Carlos Garcia-Ochoa
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Nathalie Sela
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Hemant Sharma
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Ibrahim Al Hasan
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Douglas Quan
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Bandar Al-Judaibi
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Mark Levstik
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
| | - Roberto Hernandez-Alejandro
- From the Multi-Organ Transplant Program, London Health Sciences Centre, London, Ont. (Tun-Abraham, Wanis, GarciaOchoa, Sela, Sharma, Quan, Hernandez-Alejandro); the Division of Transplantation, Prince Sultan Military Medical City, Riyadh, Saudi Arabia (Al Hasan); and the Division of Solid Organ Transplantation, University of Rochester, Rochester, NY (Al-Judaibi, Levstik, Hernandez-Alejandro)
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Badawy A, Kaido T, Uemoto S. Current Status of Liver Transplantation Using Marginal Grafts. J INVEST SURG 2018; 33:553-564. [PMID: 30457408 DOI: 10.1080/08941939.2018.1517197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Amr Badawy
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of General Surgery, Alexandria University, Alexandria, Egypt
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Jayant K, Reccia I, Virdis F, Shapiro AMJ. Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death. J Clin Med 2018; 7:425. [PMID: 30413051 PMCID: PMC6262573 DOI: 10.3390/jcm7110425] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/02/2018] [Accepted: 11/06/2018] [Indexed: 02/06/2023] Open
Abstract
AIM The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. METHODS An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. RESULTS A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). CONCLUSIONS To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.
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Affiliation(s)
- Kumar Jayant
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | - Isabella Reccia
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | | | - A M James Shapiro
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada.
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Bhutiani N, Jones JM, Wei D, Goldstein LJ, Martin RCG, Jones CM, Cannon RM. A cost analysis of early biliary strictures following orthotopic liver transplantation in the United States. Clin Transplant 2018; 32:e13396. [PMID: 30160322 DOI: 10.1111/ctr.13396] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/20/2018] [Accepted: 08/25/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION To date, the financial burden of biliary strictures (BS) after orthotopic liver transplantation (OLT) has remained largely unassessed. This study sought to approximate perioperative costs associated with early BS and delineate where in the hospital these costs are incurred. METHODS The Premier Healthcare Database was queried for patients undergoing OLT between 2010 and 2016. Patients who did and did not develop early BS were compared with respect to perioperative costs and outcome variables. Multivariable regression models were used to estimate differences between groups. RESULTS Patients who developed early BS had a longer length of stay (LOS) (35.3 days vs 17.8 days, P < 0.001) and were less likely to be discharged home (odds ratio = 0.45, P = 0.003). Development of early BS was associated with an incremental cost increase of $81 881 (45.8%, P < 0.001). The greatest relative cost increases were in radiology (+163.5%) and respiratory therapy (+157.1%), while the greatest absolute increase was in room and board (+$27 589). CONCLUSIONS Early BS after OLT result in higher costs stemming from longer LOS and increased need for various diagnostic studies and therapies. In addition to incentivizing measures that may prevent early BS, hospitals should account for these factors when developing payment schemes for OLT with payors.
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Affiliation(s)
- Neal Bhutiani
- Division of Transplantation, Hiram C. Polk Jr, MD Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Jordan M Jones
- Division of Transplantation, Hiram C. Polk Jr, MD Department of Surgery, University of Louisville, Louisville, Kentucky
| | - David Wei
- Epidemiology, Medical Devices, Johnson & Johnson, New Brunswick, New Jersey
| | - Laura J Goldstein
- Franchise Health Economics and Market Access, Ethicon, Somerville, New Jersey
| | - Robert C G Martin
- Division of Transplantation, Hiram C. Polk Jr, MD Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Christopher M Jones
- Division of Transplantation, Hiram C. Polk Jr, MD Department of Surgery, University of Louisville, Louisville, Kentucky
| | - Robert M Cannon
- Division of Transplantation, Hiram C. Polk Jr, MD Department of Surgery, University of Louisville, Louisville, Kentucky
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Kollmann D, Sapisochin G, Goldaracena N, Hansen BE, Rajakumar R, Selzner N, Bhat M, McCluskey S, Cattral MS, Greig PD, Lilly L, McGilvray ID, Ghanekar A, Grant DR, Selzner M. Expanding the donor pool: Donation after circulatory death and living liver donation do not compromise the results of liver transplantation. Liver Transpl 2018; 24:779-789. [PMID: 29604237 PMCID: PMC6099346 DOI: 10.1002/lt.25068] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 02/23/2018] [Accepted: 03/13/2018] [Indexed: 12/12/2022]
Abstract
Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1-, 3-, and 5-year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1-, 3-, and 5-year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779-789 2018 AASLD.
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Affiliation(s)
| | | | | | - Bettina E. Hansen
- Toronto Centre for Liver DiseaseToronto General HospitalOnatrioCanada
- Institute of Health Policy, Management and EvaluationUniversity of TorontoTorontoOntarioCanada
| | | | - Nazia Selzner
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | - Mamatha Bhat
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | - Stuart McCluskey
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | | | - Paul D. Greig
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - Les Lilly
- Department of Anesthesia and Pain ManagementToronto General HospitalOnatrioCanada
| | | | - Anand Ghanekar
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - David R. Grant
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - Markus Selzner
- Department of SurgeryToronto General HospitalOnatrioCanada
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40
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Jayant K, Reccia I, Virdis F, Shapiro AMJ. The Role of Normothermic Perfusion in Liver Transplantation (TRaNsIT Study): A Systematic Review of Preliminary Studies. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2018; 2018:6360423. [PMID: 29887782 PMCID: PMC5985064 DOI: 10.1155/2018/6360423] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 04/18/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The success of liver transplantation has been limited by the unavailability of suitable donor livers. The current organ preservation technique, i.e., static cold storage (SCS), is not suitable for marginal organs. Alternatively, normothermic machine perfusion (NMP) promises to recreate the physiological environment and hence holds promise for the better organ preservation. The objective of this systematic review is to provide an overview of the safety, benefits, and insight into the other potential useful parameters of NMP in the liver preservation. MATERIAL AND METHODS We searched the current literature following registration in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42018086034 for prospective trials comparing the role of NMP device to SCS in liver transplant by searching the PubMed, EMBASE, Cochrane, BIOSIS, Crossref, and Scopus databases and clinical trial registry. RESULTS The literature search identified five prospective clinical trials (four being early phase single institutional and single randomized multi-institutional) comparing 187 donor livers on NMP device to 273 donor livers on SCS. The primary outcome of interest was to assess the safety and graft survival at day 30 after transplant following NMP of the donor liver. Secondary outcomes included were early allograft dysfunction (EAD) in the first seven days; serum measures of liver functions as bilirubin, aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), and international normalized ratio (INR) on days 1-7; major complications as defined by a Clavien-Dindo score ≥ 3; and patient and graft survival and biliary complications at six months. The peaked median AST level between days 1 and 7 in the five trials was 417-1252 U/L (range 84-15009 U/L) while on NMP and 839-1474 U/L (range 153-8786 U/L) in SCS group. The median bilirubin level on day 7 ranged within 25-79 µmol/L (range 8-344 µmol/l) and 30-47.53 µmol/l (range 9-340 µmol/l) in NMP and SCS groups, respectively. A single case of PNF was reported in NMP group in the randomized trial while none of the other preliminary studies reported any in either group. There was intertrial variability in EAD which ranged within 15-56% in NMP group while being within 23-37% in SCS group. Biliary complications observed in NMP group ranged from 0 to 20%. Single device malfunction was reported in randomized controlled trial leading to renouncement of transplant while none of the other trials reported any machine failure, although two user related device errors inadvertent were reported. CONCLUSION This review outlines that NMP not only demonstrated safety and efficacy but also provided the favourable environment of organ preservation, repair, and viability assessment to donor liver prior to the transplantation with low rate of posttransplantation complication as PNF, EAD, and biliary complication; however further studies are needed to broaden our horizon.
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Affiliation(s)
- Kumar Jayant
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Isabella Reccia
- Department of Surgery and Cancer, Imperial College London, London, UK
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Hessheimer AJ, Vendrell M, Muñoz J, Ruíz Á, Díaz A, Sigüenza LF, Lanzilotta JR, Delgado Oliver E, Fuster J, Navasa M, García-Valdecasas JC, Taurá P, Fondevila C. Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model. Liver Transpl 2018; 24:665-676. [PMID: 29351369 DOI: 10.1002/lt.25013] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 12/07/2017] [Accepted: 01/06/2018] [Indexed: 02/07/2023]
Abstract
Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.
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Affiliation(s)
- Amelia J Hessheimer
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Marina Vendrell
- Departments of Anesthesia, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Javier Muñoz
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Ángel Ruíz
- Department of Hepatobiliary and Liver Transplant Surgery, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Alba Díaz
- Pathology, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Luís Flores Sigüenza
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Jorge Rodríguez Lanzilotta
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Eduardo Delgado Oliver
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Jose Fuster
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Institut de Malalties Digestives i Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Juan Carlos García-Valdecasas
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Pilar Taurá
- Departments of Anesthesia, Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Constantino Fondevila
- Department of Surgery, Institut de Malalties Digestives I Metabòliques, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, University of Barcelona, Barcelona, Spain.,Department of Hepatobiliary and Liver Transplant Surgery, Hospital Clínic, University of Barcelona, Barcelona, Spain
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42
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DCD Liver Transplant: a Meta-review of the Evidence and Current Optimization Strategies. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0193-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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43
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A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation. Am J Surg 2018; 216:959-962. [PMID: 29724406 DOI: 10.1016/j.amjsurg.2018.04.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/02/2018] [Accepted: 04/11/2018] [Indexed: 01/08/2023]
Abstract
INTRODUCTION This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). METHODS Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. RESULTS The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p < 0.001). Meta-analysis demonstrated a risk reduction of 15.7%, which translated into a NNT of 6.4. Cost associated with treating 6.4 patients was $50,353. Based on an incremental cost of $81,888 associated with PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. CONCLUSION Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT.
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Boteon YL, Afford SC, Mergental H. Pushing the Limits: Machine Preservation of the Liver as a Tool to Recondition High-Risk Grafts. CURRENT TRANSPLANTATION REPORTS 2018; 5:113-120. [PMID: 29774176 PMCID: PMC5945712 DOI: 10.1007/s40472-018-0188-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF THE REVIEW Machine perfusion (MP) is a novel technology recently introduced in liver transplantation, redefining the current practice of organ preservation and pushing the limits of high-risk liver utilisation. This review highlights the key benefits of machine perfusion over conventional static cold storage (SCS), demonstrated in human liver research and clinical transplants. RECENT FINDINGS The first clinical trials have demonstrated both safety and feasibility of MP. The most recent transplant series and result from a randomised trial suggest the technology is superior to SCS. The key benefits include extended period of organ preservation, decreased incidence of early allograft dysfunction and reduction of biliary complications. Normothermic liver perfusion allows viability testing to guide transplantability of the highest-risk organs. This technology also provides opportunities for therapeutic interventions to improve liver function and quality in organs that are currently declined for clinical use. SUMMARY Machine perfusion is likely to transform the liver preservation pathway and to improve utilisation of high-risk grafts.
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Affiliation(s)
- Yuri L. Boteon
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH UK
- National Institute for Health Research, Birmingham Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Simon C. Afford
- National Institute for Health Research, Birmingham Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Hynek Mergental
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH UK
- National Institute for Health Research, Birmingham Liver Biomedical Research Centre, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
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45
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He X, Ji F, Zhang Z, Tang Y, Yang L, Huang S, Li W, Su Q, Xiong W, Zhu Z, Wang L, Lv L, Yao J, Zhang L, Zhang L, Guo Z. Combined liver-kidney perfusion enhances protective effects of normothermic perfusion on liver grafts from donation after cardiac death. Liver Transpl 2018; 24:67-79. [PMID: 29024427 DOI: 10.1002/lt.24954] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Revised: 09/18/2017] [Accepted: 09/26/2017] [Indexed: 12/31/2022]
Abstract
It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C). Livers were preserved for 6 hours and reperfused ex vivo for 2 hours to simulate transplantation or were transplanted in situ. During perfusion, group C showed an improved acid-base and biochemical environment in the circuit over group B. After reperfusion, the architecture of the liver grafts was best preserved in group C, followed by group B, then group A, as shown by the histology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining of both hepatocytes and biliary epithelium. Ki-67 staining showed substantial hepatocyte proliferation and biliary epithelial regeneration after perfusion in group B and group C. Group C produced more bile in the reperfusion phase than those in group A and group B, with more physiological bile composition and less severe biliary epithelium injury. Von Willebrand factor-positive endothelial cells and E-selectin expression decreased in both group B and group C. Combined liver-kidney NMP not only produced more adenosine triphosphate, protected the nitric oxide signaling pathway, but also diminished oxidative stress (high mobility group box-1 protein and 8-hydroxy-2-deoxy guanosine levels) and inflammatory cytokine (IL6 and IL8) release when compared with liver-alone NMP and CS. In addition, the 7-day survival rate of liver transplant recipients was higher in group C than that in groups A and B. In conclusion, combined liver-kidney NMP can better protect DCD livers from warm ischemia and reperfusion injury probably by maintaining the stability of the internal environment and by abolishing oxidative stress injury. Liver Transplantation 24 67-79 2018 AASLD.
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Affiliation(s)
- Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Fei Ji
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Pediatric Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zhiheng Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Yunhua Tang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Lu Yang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shanzhou Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Wenwen Li
- Laboratory Animal Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiao Su
- Laboratory Animal Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Xiong
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zebin Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Linhe Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Lei Lv
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Jiyou Yao
- Surgical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Linan Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Longjuan Zhang
- Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
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46
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Bohorquez H, Loss GE. Response to "Minimization of Ischemic Cholangiopathy in Donation After Cardiac Death Liver Transplantation: Is it Thrombolytic Therapy or Warm Ischemic Time Stringency and Donor Bile Duct Flush?". Am J Transplant 2018; 18:276-277. [PMID: 28801953 DOI: 10.1111/ajt.14460] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- H Bohorquez
- Multi-Organ Transplant Institute, New Orleans, LA, USA.,Ochsner School of Medicine, University of Queensland, New Orleans, LA, USA
| | - G E Loss
- Multi-Organ Transplant Institute, New Orleans, LA, USA.,Ochsner School of Medicine, University of Queensland, New Orleans, LA, USA
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47
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Giorgakis E, Khorsandi SE, Jassem W, Heaton N. Minimization of Ischemic Cholangiopathy in Donation After Cardiac Death Liver Transplantation: Is It Thrombolytic Therapy or Warm Ischemic Time Stringency and Donor Bile Duct Flush? Am J Transplant 2018; 18:274-275. [PMID: 28710889 DOI: 10.1111/ajt.14429] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- E Giorgakis
- Division of Transplant Surgery, Mayo Clinic, Phoenix, AZ.,Institute of Liver Studies, King's College Hospital, London, UK
| | - S E Khorsandi
- Institute of Liver Studies, King's College Hospital, London, UK
| | - W Jassem
- Institute of Liver Studies, King's College Hospital, London, UK
| | - N Heaton
- Institute of Liver Studies, King's College Hospital, London, UK
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48
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Vining CC, Ecker BL, Abt PL, Olthoff KM. Donation after cardiac death in the hepatocellular carcinoma patient: Same indication? Liver Transpl 2017; 23:S27-S33. [PMID: 28846212 DOI: 10.1002/lt.24862] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 08/14/2017] [Accepted: 08/24/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Charles C Vining
- Department of Surgery, University of Pennsylvania, Philadelphia, PA
| | - Brett L Ecker
- Department of Surgery, University of Pennsylvania, Philadelphia, PA
| | - Peter L Abt
- Department of Surgery, University of Pennsylvania, Philadelphia, PA
| | - Kim M Olthoff
- Department of Surgery, University of Pennsylvania, Philadelphia, PA
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49
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Croome KP, Lee DD, Nguyen JH, Keaveny AP, Taner CB. Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores. Am J Transplant 2017; 17:2420-2427. [PMID: 28556380 DOI: 10.1111/ajt.14383] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/04/2017] [Accepted: 05/11/2017] [Indexed: 01/25/2023]
Abstract
Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.
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Affiliation(s)
- K P Croome
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - D D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - J H Nguyen
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - A P Keaveny
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - C B Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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50
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Abt PL, Goldberg DS. Retransplantation After a Failed Donation After Circulatory Determination of Death Liver Transplant: MELD Exception Priority and Second Chances. Am J Transplant 2017; 17:2240-2242. [PMID: 28621875 DOI: 10.1111/ajt.14395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 06/02/2017] [Accepted: 06/08/2017] [Indexed: 01/25/2023]
Affiliation(s)
- P L Abt
- Division of Transplantation, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - D S Goldberg
- Division of Gastroenterology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, Philadelphia, PA.,Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA
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