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Li Q, Liu Y, Wang Y, Shan X, Liu C, Li Z, Cao J, Dou J, Xu G, Wang Q, Qie X. Bicarbonate ringer's solution could improve the intraoperative acid-base equilibrium and reduce hepatocellular enzyme levels after deceased donor liver transplantation: a randomized controlled study. BMC Anesthesiol 2023; 23:418. [PMID: 38114893 PMCID: PMC10729548 DOI: 10.1186/s12871-023-02383-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 12/12/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Bicarbonate Ringer's (BR) solution is a direct liver and kidney metabolism-independent HCO3- buffering system. We hypothesized that BR solution would be more effective in improving acid-base equilibrium and more conducive to better liver function than Acetate Ringer's (AR) solution in conventional orthotopic liver transplantation (OLT) patients. METHODS Sixty-nine adult patients underwent OLT. Patients in the bicarbonate and acetate groups received BR solution or AR solution as infused crystalloids and graft washing solution, respectively. The primary outcome was the effect on pH and base excess (BE) levels. The secondary outcome measures were the incidence and volume of intraoperative 5% sodium bicarbonate infusion and laboratory indicates of liver and kidney function. RESULTS The pH and absolute BE values changed significantly during the anhepatic phase and immediately after transplanted liver reperfusion in the bicarbonate group compared with the acetate group (all P < 0.05). The incidence and volume of 5% sodium bicarbonate infusion were lower in the bicarbonate group than in the acetate group (all P < 0.05). The aspartate transaminase (AST) level at 7 postoperative days and the creatine level at 30 postoperative days were significantly higher in the acetate group than in the bicarbonate group (all P < 0.05). CONCLUSION Compared with AR solution, BR solution was associated with improved intraoperative acid-base balance and potentially protected early postoperative liver graft function and reduced late-postoperative renal injury.
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Affiliation(s)
- Qingkai Li
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Ying Liu
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Yanan Wang
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Xin Shan
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Chunxiao Liu
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Zhihua Li
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Jinglin Cao
- Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Jian Dou
- Department of Hepatobiliary Surgery, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Guanjie Xu
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Qiujun Wang
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China
| | - Xiaojuan Qie
- Department of Aesthesiology, The Third Hospital of Hebei Medical University, Shi Jiazhuang, 050051, China.
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Tingle SJ, Bramley R, Goodfellow M, Thompson ER, McPherson S, White SA, Wilson CH. Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study. Transplantation 2023; 107:2533-2544. [PMID: 37069657 DOI: 10.1097/tp.0000000000004610] [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: 04/19/2023]
Abstract
BACKGROUND Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor "liver blood tests" on transplant outcomes. METHODS This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019); adjusted regressions models were used to assess the effect of donor "liver blood tests" on outcomes. RESULTS A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044). CONCLUSIONS Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.
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Affiliation(s)
- Samuel J Tingle
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Rebecca Bramley
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Michael Goodfellow
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Emily R Thompson
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Stuart McPherson
- Department of Hepatology, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Steve A White
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Colin H Wilson
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
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3
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Gong JL, Yu J, Wang TL, He XS, Tang YH, Zhu XF. Application of extended criteria donor grafts in liver transplantation for acute-on-chronic liver failure: A retrospective cohort study. World J Gastroenterol 2023; 29:5630-5640. [PMID: 38077155 PMCID: PMC10701327 DOI: 10.3748/wjg.v29.i41.5630] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/24/2023] [Accepted: 10/23/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND There is no consensus on the usage of extended criteria donor (ECD) grafts in liver transplantation (LT) for acute-on-chronic liver failure (ACLF) patients. AIM To summarize the experience of using ECD livers in ACLF-LT. METHODS A retrospective cohort study was conducted, enrolling patients who underwent LT at the First Affiliated Hospital of Sun Yat-Sen University from January 2015 to November 2021. The patients were divided into ECD and non-ECD groups for analysis. RESULTS A total of 145 recipients were enrolled in this study, of which ECD and non-ECD recipients accounted for 53.8% and 46.2%, respectively. Donation after cardiac death (DCD) recipients accounted for the minority compared with donation after brain death (DBD) recipients (16.6% vs 83.4%). Neither overall survival nor graft survival significantly differed between ECD and non-ECD and DCD and DBD recipients. ECD grafts were associated with a significantly higher incidence of early allograft dysfunction (EAD) than non-ECD grafts (67.9% vs 41.8%, P = 0.002). Postoperative outcomes between DCD and DBD recipients were comparable (P > 0.05). ECD graft (P = 0.009), anhepatic phase (P = 0.034) and recipient gamma glutamyltransferase (P = 0.016) were independent risk factors for EAD. Recipient preoperative number of extrahepatic organ failures > 2 (P = 0.015) and intraoperative blood loss (P = 0.000) were independent predictors of poor post-LT survival. CONCLUSION Although related to a higher risk of EAD, ECD grafts can be safely used in ACLF-LT. The main factors affecting post-LT survival in ACLF patients are their own severe preoperative disease and intraoperative blood loss.
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Affiliation(s)
- Jin-Long Gong
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Jia Yu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
- Department of Gastroenterology Surgery, The First Affiliated Hospital of University of South China, Hengyang 421005, Hunan Province, China
| | - Tie-Long Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Shun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Yun-Hua Tang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Xiao-Feng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
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Lai Q, Melandro F, Manzia TM, Spoletini G, Crovetto A, Gallo G, Hassan R, Mennini G, Angelico R, Avolio AW, Berrevoet F, Abreu de Carvalho L, Agnes S, Tisone G, Rossi M. The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation. J Clin Med 2023; 12:4744. [PMID: 37510859 PMCID: PMC10380680 DOI: 10.3390/jcm12144744] [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: 05/31/2023] [Revised: 07/03/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. METHODS This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. RESULTS Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. CONCLUSIONS Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
| | - Fabio Melandro
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
| | - Tommaso M. Manzia
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00173 Rome, Italy; (T.M.M.); (R.A.); (G.T.)
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (G.S.); (A.W.A.); (S.A.)
| | - Anna Crovetto
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (A.C.); (F.B.); (L.A.d.C.)
| | - Gaetano Gallo
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
| | - Redan Hassan
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
| | - Roberta Angelico
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00173 Rome, Italy; (T.M.M.); (R.A.); (G.T.)
| | - Alfonso W. Avolio
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (G.S.); (A.W.A.); (S.A.)
| | - Frederik Berrevoet
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (A.C.); (F.B.); (L.A.d.C.)
| | - Luís Abreu de Carvalho
- Department of General and HPB Surgery and Liver Transplantation, Ghent University Hospital, 9000 Ghent, Belgium; (A.C.); (F.B.); (L.A.d.C.)
| | - Salvatore Agnes
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (G.S.); (A.W.A.); (S.A.)
| | - Giuseppe Tisone
- HPB and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, 00173 Rome, Italy; (T.M.M.); (R.A.); (G.T.)
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umbertot I of Rome, 00185 Rome, Italy; (F.M.); (G.G.); (R.H.); (G.M.); (M.R.)
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5
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Schlegel A, Mergental H, Fondevila C, Porte RJ, Friend PJ, Dutkowski P. Machine perfusion of the liver and bioengineering. J Hepatol 2023; 78:1181-1198. [PMID: 37208105 DOI: 10.1016/j.jhep.2023.02.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 05/21/2023]
Abstract
With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion - one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
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Affiliation(s)
- Andrea Schlegel
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, 20122, Italy; Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland
| | - Hynek Mergental
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, United Kingdom
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Robert J Porte
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Peter J Friend
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland.
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