18 results on '"H. Mergental"'
Search Results
2. How Machine Perfusion Ameliorates Hepatic Ischaemia Reperfusion Injury.
- Author
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Clarke G, Mergental H, Hann A, Perera MTPR, Afford SC, and Mirza DF
- Subjects
- Animals, Humans, Graft Survival, Liver blood supply, Liver Transplantation methods, Organ Preservation methods, Perfusion, Reperfusion Injury therapy
- Abstract
The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ-it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4-10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft's response to this.
- Published
- 2021
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3. Reply to 'Hypothermic machine perfusion before viability testing of previously discarded human livers'.
- Author
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Mergental H, Laing RW, Afford SC, and Mirza DF
- Subjects
- Humans, Perfusion, Liver, Liver Transplantation
- Published
- 2021
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- View/download PDF
4. Lactate measurements in an integrated perfusion machine for human livers.
- Author
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Stephenson BTF, Afford SC, Mergental H, and Mirza DF
- Subjects
- Humans, Perfusion, Lactates, Liver
- Published
- 2020
- Full Text
- View/download PDF
5. Transplantation of discarded livers following viability testing with normothermic machine perfusion.
- Author
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Mergental H, Laing RW, Kirkham AJ, Perera MTPR, Boteon YL, Attard J, Barton D, Curbishley S, Wilkhu M, Neil DAH, Hübscher SG, Muiesan P, Isaac JR, Roberts KJ, Abradelo M, Schlegel A, Ferguson J, Cilliers H, Bion J, Adams DH, Morris C, Friend PJ, Yap C, Afford SC, and Mirza DF
- Subjects
- Aged, Female, Humans, Liver metabolism, Male, Middle Aged, Non-Randomized Controlled Trials as Topic, Organ Preservation statistics & numerical data, Perfusion methods, Prospective Studies, Survival Analysis, Temperature, Time Factors, Tissue and Organ Harvesting methods, Tissue and Organ Harvesting statistics & numerical data, Graft Survival physiology, Liver physiology, Liver Function Tests methods, Liver Transplantation methods, Organ Preservation methods, Tissue Donors statistics & numerical data
- Abstract
There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.
- Published
- 2020
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6. The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver.
- Author
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Boteon YL, Laing RW, Schlegel A, Wallace L, Smith A, Attard J, Bhogal RH, Reynolds G, Perera MTPR, Muiesan P, Mirza DF, Mergental H, and Afford SC
- Subjects
- Adult, Aged, Blood Substitutes, Cadaver, Female, Humans, Liver blood supply, Liver Transplantation, Male, Middle Aged, Oxidative Stress, Reperfusion Injury prevention & control, Tissue Donors, Cold Ischemia, Energy Metabolism, Hemoglobins metabolism, Liver metabolism, Organ Preservation methods, Oxygen metabolism, Perfusion methods, Warm Ischemia
- Abstract
Introduction: The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate., Methods: Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed., Results: The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups., Conclusion: The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate-cold-to-warm MP-mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability., Competing Interests: The machine perfusion research was funded by the Queen Elizabeth Hospital Birmingham Charity’s Liver Foundation UK. YLB is funded by the NIHR Wellcome Trust. Hemopure® was provided free of charge by Hemoglobin Oxygen Therapeutics LLC. The company has not had any role in the study design, data collection, analysis, interpretation or manuscript preparation. The authors are employees of the University Hospital Birmingham or the University of Birmingham and none of them received any payment or have any conflict of interest related to this manuscript. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2019
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7. The Emerging Importance of Liver Sinusoidal Endothelial Cells in Regulating Injury during Machine Perfusion of Deceased Liver Donors.
- Author
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Bhogal RH, Mergental H, Mirza DF, and Afford SC
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- Animals, Donor Selection, Endothelial Cells metabolism, Endothelial Cells pathology, Graft Survival, Humans, Liver metabolism, Liver pathology, Liver Transplantation adverse effects, Organ Preservation adverse effects, Organ Preservation instrumentation, Perfusion adverse effects, Perfusion instrumentation, Reperfusion Injury etiology, Reperfusion Injury metabolism, Reperfusion Injury pathology, Risk Factors, Signal Transduction, Treatment Outcome, Waiting Lists, Endothelial Cells transplantation, Liver surgery, Liver Transplantation methods, Organ Preservation methods, Perfusion methods, Reperfusion Injury prevention & control, Tissue Donors supply & distribution
- Abstract
While majority of liver transplants worldwide continue to be performed using deceased donor organs, the demands for donor livers continues to exceed the current supply. In an attempt to maximize the number of potentially usable donor livers and expand the current donor pool, there is intense global research by various groups exploring the role of machine perfusion in the liver transplantation, particularly with respect to the machine perfusion of extended-criteria liver donors. In this review, the authors summarize the current field of machine perfusion strategies as applied to deceased donor liver transplantation and how therapeutic targeting of the liver sinusoidal endothelial cell may improve the quality of donor livers., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)
- Published
- 2018
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8. Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation.
- Author
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Angelico R, Gerlach UA, Gunson BK, Neil D, Mergental H, Isaac J, Muiesan P, Mirza D, and Perera MTP
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- Adolescent, Adult, Aged, Biopsy, Female, Follow-Up Studies, Graft Rejection immunology, Graft Survival, Humans, Male, Middle Aged, Postoperative Complications, Postoperative Period, Proportional Hazards Models, Prospective Studies, Retrospective Studies, Risk, Time Factors, Treatment Outcome, Ultrasonography, Doppler, United Kingdom, Young Adult, Cholestasis complications, Cholestasis etiology, Liver pathology, Liver Transplantation adverse effects
- Abstract
Background: Causes of severe cholestasis after liver transplantation (LT) are multi-factorial. Although the etiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge., Methods: This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT during the study period, 90-day graft failure occurred in 129 (8%) cases; a total of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 μmol/L; alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft biopsies, radiological investigations, and clinical outcome were analyzed., Results: All patients had persistent abnormal liver biochemistry. Doppler ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases. Donor-specific antibodies were detected in all patients tested. Biliary anatomy was studied in detail in 9 (20%) patients, all presenting biliary strictures. The majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%)., Conclusions: Unresolving severe cholestasis after LT is a key parameter predicting patient/allograft outcome. Histologically, rejection seems to overlap with biliary strictures; hence, allograft biopsy with signs of rejection should not be a reason to overlook biliary problems, in particular when biliary features are present. Only extensive radiological investigation/intervention or retransplantation prevents patient/allograft loss.
- Published
- 2018
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9. An effective protocol for pharmacological defatting of primary human hepatocytes which is non-toxic to cholangiocytes or intrahepatic endothelial cells.
- Author
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Boteon YL, Wallace L, Boteon APCS, Mirza DF, Mergental H, Bhogal RH, and Afford S
- Subjects
- Bile Ducts cytology, Bile Ducts drug effects, Bile Ducts metabolism, Cell Survival drug effects, Cells, Cultured, Endothelial Cells cytology, Endothelial Cells drug effects, Endothelial Cells metabolism, Epithelial Cells cytology, Epithelial Cells drug effects, Epithelial Cells metabolism, Fatty Acids metabolism, Fatty Liver metabolism, Hep G2 Cells, Hepatocytes cytology, Hepatocytes metabolism, Humans, Ketone Bodies metabolism, Liver cytology, Liver metabolism, Fats metabolism, Fatty Liver drug therapy, Hepatocytes drug effects, Liver drug effects, Triglycerides metabolism
- Abstract
Introduction: Pharmacological defatting of rat hepatocytes and hepatoma cell lines suggests that the same method could be used to ameliorate macrovesicular steatosis in moderate to severely fatty livers. However there is no data assessing the effects of those drugs on primary human liver cells. We aimed to determine the effectiveness of a pharmacological cocktail in reducing the in vitro lipid content of primary human hepatocytes (PHH). In addition we sought to determine the cytotoxicity of the cocktail towards non-parenchymal liver cells., Methods: Steatosis was induced in PHH by supplementation with a combination of saturated and unsaturated free fatty acids. This was followed by addition of a defatting drug cocktail for up to 48 hours. The same experimental method was used with human intra-hepatic endothelial cells (HIEC) and human cholangiocytes. MTT assay was used to assess cell viability, triglyceride quantification and oil red O staining were used to determine intracellular lipids content whilst ketone bodies were measured in the supernatants following experimentation., Results: Incubation of fat loaded PHH with the drugs over 48 hours reduced the intracellular lipid area by 54%, from 12.85% to 5.99% (p = 0.002) (percentage of total oil red O area), and intracellular triglyceride by 35%, from 28.24 to 18.30 nmol/million of cells (p<0.001). Total supernatant ketone bodies increased 1.4-fold over 48 hours in the defatted PHH compared with vehicle controls (p = 0.002). Moreover incubation with the drugs for 48 hours increased the viability of PHH by 11%, cholangiocytes by 25% whilst having no cytotoxic effects on HIEC., Conclusion: These data demonstrate that pharmacological intervention can significantly decrease intracellular lipid content of PHH, increase fatty acids β-oxidation whilst being non-toxic to PHH, HIEC or cholangiocytes., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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10. A randomized trial of normothermic preservation in liver transplantation.
- Author
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Nasralla D, Coussios CC, Mergental H, Akhtar MZ, Butler AJ, Ceresa CDL, Chiocchia V, Dutton SJ, García-Valdecasas JC, Heaton N, Imber C, Jassem W, Jochmans I, Karani J, Knight SR, Kocabayoglu P, Malagò M, Mirza D, Morris PJ, Pallan A, Paul A, Pavel M, Perera MTPR, Pirenne J, Ravikumar R, Russell L, Upponi S, Watson CJE, Weissenbacher A, Ploeg RJ, and Friend PJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Allografts pathology, Allografts physiopathology, Allografts standards, Bile Ducts pathology, Bile Ducts physiology, Bile Ducts physiopathology, Female, Graft Survival, Humans, Length of Stay, Liver enzymology, Liver Transplantation adverse effects, Male, Middle Aged, Organ Preservation adverse effects, Perfusion, Survival Analysis, Tissue Donors supply & distribution, Tissue and Organ Harvesting adverse effects, Treatment Outcome, Waiting Lists, Young Adult, Allografts physiology, Liver physiology, Liver Transplantation methods, Organ Preservation methods, Temperature, Tissue and Organ Harvesting methods
- Abstract
Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.
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- 2018
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11. Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion.
- Author
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Boteon YL, Laing R, Mergental H, Reynolds GM, Mirza DF, Afford SC, and Bhogal RH
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- Autophagy drug effects, Humans, Liver blood supply, Liver cytology, Liver drug effects, Organ Preservation adverse effects, Organ Preservation methods, Perfusion adverse effects, Perfusion methods, Protective Agents pharmacology, Protective Agents therapeutic use, Reperfusion Injury etiology, Reperfusion Injury prevention & control, Signal Transduction drug effects, Signal Transduction physiology, Temperature, Autophagy physiology, Endothelial Cells physiology, Liver physiopathology, Liver Transplantation adverse effects, Reperfusion Injury physiopathology
- Abstract
Ischaemia-reperfusion injury (IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells (LSEC). Recent evidence suggests that LSEC co-ordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion (NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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- 2017
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12. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial.
- Author
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Laing RW, Mergental H, Yap C, Kirkham A, Whilku M, Barton D, Curbishley S, Boteon YL, Neil DA, Hübscher SG, Perera MTPR, Muiesan P, Isaac J, Roberts KJ, Cilliers H, Afford SC, and Mirza DF
- Subjects
- Feasibility Studies, Humans, Non-Randomized Controlled Trials as Topic, Perfusion methods, Practice Guidelines as Topic, Prospective Studies, Time Factors, Tissue Survival, Tissue and Organ Procurement methods, Transplant Recipients, Liver metabolism, Liver Transplantation, Organ Preservation methods, Tissue and Organ Procurement standards
- Abstract
Introduction: The use of marginal or extended criteria donor livers is increasing. These organs carry a greater risk of initial dysfunction and early failure, as well as inferior long-term outcomes. As such, many are rejected due to a perceived risk of use and use varies widely between centres. Ex situ normothermic machine perfusion of the liver (NMP-L) may enable the safe transplantation of organs that meet defined objective criteria denoting their high-risk status and are currently being declined for use by all the UK transplant centres., Methods and Analysis: Viability testing and transplantation of marginal livers is an open-label, non-randomised, prospective, single-arm trial designed to determine whether currently unused donor livers can be salvaged and safely transplanted with equivalent outcomes in terms of patient survival. The procured rejected livers must meet predefined criteria that objectively denote their marginal condition. The liver is subjected to NMP-L following a period of static cold storage. Organs metabolising lactate to ≤2.5 mmol/L within 4 hours of the perfusion commencing in combination with two or more of the following parameters-bile production, metabolism of glucose, a hepatic arterial flow rate ≥150 mL/min and a portal venous flow rate ≥500 mL/min, a pH ≥7.30 and/or maintain a homogeneous perfusion-will be considered viable and transplanted into a suitable consented recipient. The coprimary outcome measures are the success rate of NMP-L to produce a transplantable organ and 90-day patient post-transplant survival., Ethics and Dissemination: The protocol was approved by the National Research Ethics Service (London-Dulwich Research Ethics Committee, 16/LO/1056), the Medicines and Healthcare Products Regulatory Agency and is endorsed by the National Health Service Blood and Transplant Research, Innovation and Novel Technologies Advisory Group. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications., Trial Registration Number: NCT02740608; Pre-results., Competing Interests: Competing interests: RWL and YB receive salary as Wellcome Trust research fellows., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2017
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13. The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.
- Author
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Laing RW, Bhogal RH, Wallace L, Boteon Y, Neil DAH, Smith A, Stephenson BTF, Schlegel A, Hübscher SG, Mirza DF, Afford SC, and Mergental H
- Subjects
- Adult, Aged, Apoptosis, Blood Substitutes toxicity, Cells, Cultured, Energy Metabolism drug effects, Female, Hemoglobins toxicity, Hepatectomy, Humans, Liver metabolism, Liver pathology, Liver surgery, Male, Middle Aged, Necrosis, Organ Preservation adverse effects, Oxygen Consumption drug effects, Perfusion adverse effects, Reactive Oxygen Species metabolism, Reperfusion Injury etiology, Reperfusion Injury metabolism, Reperfusion Injury pathology, Time Factors, Tissue Survival drug effects, Blood Substitutes pharmacology, Hemoglobins pharmacology, Liver drug effects, Organ Preservation methods, Perfusion methods, Reperfusion Injury prevention & control
- Abstract
Background: Normothermic machine perfusion of the liver (NMP-L) is a novel technique that preserves liver grafts under near-physiological conditions while maintaining their normal metabolic activity. This process requires an adequate oxygen supply, typically delivered by packed red blood cells (RBC). We present the first experience using an acellular hemoglobin-based oxygen carrier (HBOC) Hemopure in a human model of NMP-L., Methods: Five discarded high-risk human livers were perfused with HBOC-based perfusion fluid and matched to 5 RBC-perfused livers. Perfusion parameters, oxygen extraction, metabolic activity, and histological features were compared during 6 hours of NMP-L. The cytotoxicity of Hemopure was also tested on human hepatic primary cell line cultures using an in vitro model of ischemia reperfusion injury., Results: The vascular flow parameters and the perfusate lactate clearance were similar in both groups. The HBOC-perfused livers extracted more oxygen than those perfused with RBCs (O2 extraction ratio 13.75 vs 9.43 % ×10 per gram of tissue, P = 0.001). In vitro exposure to Hemopure did not alter intracellular levels of reactive oxygen species, and there was no increase in apoptosis or necrosis observed in any of the tested cell lines. Histological findings were comparable between groups. There was no evidence of histological damage caused by Hemopure., Conclusions: Hemopure can be used as an alternative oxygen carrier to packed red cells in NMP-L perfusion fluid.
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- 2017
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14. Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation.
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Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BT, Cilliers H, Neil DA, Hübscher SG, Afford SC, and Mirza DF
- Subjects
- Adult, Aged, Allografts, Female, Follow-Up Studies, Graft Rejection prevention & control, Humans, Liver blood supply, Liver Function Tests, Male, Middle Aged, Outcome Assessment, Health Care, Pilot Projects, Primary Graft Dysfunction prevention & control, Warm Ischemia, Liver metabolism, Liver Transplantation, Organ Preservation, Perfusion methods, Tissue Donors supply & distribution, Tissue Survival, Tissue and Organ Procurement methods
- Abstract
The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT., (© Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.)
- Published
- 2016
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15. Long-term follow-up after endovascular treatment of hepatic venous outflow obstruction following liver transplantation.
- Author
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Pitchaimuthu M, Roll GR, Zia Z, Olliff S, Mehrzad H, Hodson J, Gunson BK, Perera MT, Isaac JR, Muiesan P, Mirza DF, and Mergental H
- Subjects
- Adult, Aged, Databases, Factual, End Stage Liver Disease complications, Follow-Up Studies, Graft Survival, Humans, Immunosuppression Therapy, Middle Aged, Pressure, Prospective Studies, Retrospective Studies, Treatment Outcome, End Stage Liver Disease surgery, Endovascular Procedures methods, Hepatic Veins surgery, Liver blood supply, Liver Transplantation adverse effects
- Abstract
Hepatic venous outflow obstruction (HVOO) is a rare complication after liver transplantation (LT) associated with significant morbidity and reduced graft survival. Endovascular intervention has become the first-line treatment for HVOO, but data on long-term outcomes are lacking. We have analysed outcomes after endovascular intervention for HVOO in 905 consecutive patients who received 965 full-size LT at our unit from January 2007 to June 2014. There were 27 (3%) patients who underwent hepatic venogram for suspected HVOO, with persistent ascites being the most common symptom triggering the investigation (n = 19, 70%). Of those, only 10 patients demonstrated either stricture or pressure gradient over 10 mmHg on venogram, which represents a 1% incidence of HVOO. The endovascular interventions were balloon dilatation (n = 3), hepatic vein stenting (n = 4) and stenting with dilatation (n = 3). Two patients required restenting due to stent migration. The symptoms of HVOO completely resolved in all but one patient, with a median follow-up period of 74 (interquartile range 39-89) months. There were no procedure-related complications or mortality. In conclusion, the incidence of HVOO in patients receiving full-size LT is currently very low. Endovascular intervention is an effective and safe procedure providing symptom relief with long-lasting primary patency., (© 2016 Steunstichting ESOT.)
- Published
- 2016
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16. Preimplant Normothermic Liver Perfusion of a Suboptimal Liver Donated After Circulatory Death.
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Watson CJ, Kosmoliaptsis V, Randle LV, Russell NK, Griffiths WJ, Davies S, Mergental H, and Butler AJ
- Subjects
- Humans, Male, Middle Aged, Organ Preservation, Prognosis, Tissue Donors, Heart Arrest, Liver blood supply, Liver Transplantation, Perfusion, Tissue and Organ Procurement methods
- Abstract
Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of preimplant normothermic perfusion of a suboptimal liver from a 57-year-old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life-supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the liver was subject to normothermic machine perfusion with a plasma-free red cell-based perfusate. Perfusate lactate level fell from 7.2 to 0.3 mmol/L within 74 minutes of ex situ perfusion, at which point perfusate alanine transaminase level was 1152 IU/L and urea concentration was 9.4 mmol/L. After 132 minutes, normothermic perfusion was stopped and implantation begun. After transplantation, the patient made an uneventful recovery and was discharged on day 8; liver biochemistry was normal by day 19 and has remained normal thereafter. Donor common bile duct excised at implantation showed preservation of peribiliary glands, and cholangiography 6 months posttransplantation showed no evidence of cholangiopathy. Preimplant ex situ normothermic perfusion of the liver appears to be a promising way to evaluate a marginal liver before transplantation and may modify the response to ischemia., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2016
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17. The effect of end-ischaemic normothermic machine perfusion on donor hepatic artery endothelial integrity
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J, Attard, D, Sneiders, R, Laing, Y, Boteon, H, Mergental, J, Isaac, D F, Mirza, S, Afford, H, Hartog, D A H, Neil, and M T P R, Perera
- Subjects
Perfusion ,Hepatic Artery ,Liver ,Humans ,Endothelium ,Organ Preservation - Abstract
Ex vivo normothermic machine liver perfusion (NMLP) involves artificial cannulation of vessels and generation of flow pressures. This could lead to shear stress-induced endothelial damage, predisposing to vascular complications, or improved preservation of donor artery quality. This study aims to assess the spatial donor hepatic artery (HA) endothelial quality downstream of the cannulation site after end-ischaemic NMLP.Remnant HA segments from the coeliac trunk up to the gastroduodenal artery branching were obtained after NMLP (n = 15) and after static cold storage (SCS) preservation (n = 15). Specimens were fixed in 10% neutral buffered formalin and sectioned at pre-determined anatomical sites downstream of the coeliac trunk. CD31 immunohistostaining was used to assess endothelial integrity by a 5-point ordinal scale (grade 0: intact endothelial lining, grade 5: complete denudation). Endothelial integrity after SCS was used as a control for the state of the endothelium at commencement of NMP.In the SCS specimens, regardless of the anatomical site, near complete endothelial denudation was present throughout the HA (median scores 4.5-5). After NMLP, significantly less endothelial loss in the distal HA was present compared to SCS grafts (NMLP vs. SCS: median grade 3 vs. 4.5; p = 0.042). In NMLP specimens, near complete endothelial denudation was present at the cannulation site in all cases (median grade: 5), with significantly less loss of the endothelial lining the further from the cannulation site (proximal vs. distal, median grade 5 vs. 3; p = 0.005).Loss of endothelial lining throughout the HA after SCS and at the cannulation site after NMLP suggests extensive damage related to surgical handling and preservation injury. Gradual improved endothelial lining along more distal sites of the HA after NMLP indicates potential for re-endothelialisation. The regenerative effect of NMLP on artery quality seems to occur to a greater extent further from the cannulation site. Therefore, arterial cannulation for machine perfusion of liver grafts should ideally be as proximal as possible on the coeliac trunk or aortic patch, while the site of anastomosis should preferentially be attempted distal on the common HA.
- Published
- 2021
18. Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative)
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A. Hann, H. Lembach, A. Nutu, B. Dassanayake, S. Tillakaratne, S. C. McKay, A. P. C. S. Boteon, Y. L. Boteon, H. Mergental, N. Murphy, M. N. Bangash, D. A. H. Neil, J. L. Issac, N. Javed, T. Faulkner, D. Bennet, R. Moore, S. Vasanth, G. Subash, J. Cuell, R. Rao, H. Cilliers, S. Russel, G. Haydon, D. Mutimer, K. J. Roberts, D. F. Mirza, J. Ferguson, D. Bartlett, J. R. Isaac, N. Rajoriya, M. J. Armstrong, H. Hartog, and M. T. P. R. Perera
- Subjects
Perfusion ,Liver ,Graft Survival ,Humans ,Surgery ,Organ Preservation ,Liver Transplantation - Abstract
Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion.A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival.The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P0.001).In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.
- Published
- 2021
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