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Micó-Carnero M, Rojano-Alfonso C, Maroto-Serrat C, Cutrin JC, Casillas-Ramírez A, Peralta C. Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease. Front Cell Dev Biol 2025; 12:1455258. [PMID: 39839674 PMCID: PMC11747040 DOI: 10.3389/fcell.2024.1455258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025] Open
Abstract
Introduction Grafts with alcohol-associated liver disease (ALD) subjected to prolonged cold ischaemia from donors after brain death (DBD) are typically unsuitable for transplantation. Here, we investigated the role of growth hormone (GH) in livers with ALD from DBDs and its relationship with vascular endothelial growth factor A (VEGFA) and VEGFB. Methods Livers from rats fed ethanol for 6 weeks and with brain death (BD) were cold stored for 24 h and subjected to ex vivo reperfusion. Hepatic damage and proliferative and inflammatory parameters were analysed after BD, before graft retrieval, and after reperfusion. Survival was monitored using an in vivo transplantation model. Results In DBDs, the administration of GH, which increased the levels in the intestine but not in the liver, induced the generation of both VEGFA and VEGFB in the intestine and protected against hepatic damage caused by BD before retrieving liver grafts from donors. However, VEGFA was the only factor that protected against damage after cold ischemia and reperfusion, which also increased the survival of the recipients. Discussion In conclusion, the signalling pathway and beneficial properties of the GH-VEGFA/VEGFB pathway, in which the intestine-liver axis plays a key role, were disrupted when grafts with ALD from DBDs were retrieved from donors and subjected to cold ischemia and reperfusion.
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Affiliation(s)
- Marc Micó-Carnero
- Department of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Carlos Rojano-Alfonso
- Department of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Cristina Maroto-Serrat
- Department of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Juan Carlos Cutrin
- Molecular Biotechnology Center II “Guido Tarone”, Department of Molecular Biotechnologies and Science for the Health, University of Torino, Torino, Italy
| | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria, IMSS-BIENESTAR, Ciudad Victoria, Mexico
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros, Mexico
| | - Carmen Peralta
- Department of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Li Y, Liu X, Zhang C, Tao R, Pan B, Liu W, Jiang D, Hu F, Xu Z, Tan D, Ou Y, Li X, You Y, Zhang L. A Brief Model Evaluated Outcomes After Liver Transplantation Based on the Matching of Donor Graft and Recipient. Clin Transl Gastroenterol 2025; 16:e00761. [PMID: 39166764 PMCID: PMC11756882 DOI: 10.14309/ctg.0000000000000761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 07/31/2024] [Indexed: 08/23/2024] Open
Abstract
INTRODUCTION A precise model for predicting outcomes is needed to guide perioperative management. With the development of the liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes. METHODS The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver-operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications. RESULTS Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) ( P = 0.012) and Model for End-Stage Liver Disease (MELD) ( P = 0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06 < grade 2 ≤ 1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications. DISCUSSION The model integrating variables from graft donors and recipients made the prediction more accurate and available. CMI provided new insight into outcome evaluation and risk factor management of LT.
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Affiliation(s)
- Yuancheng Li
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xingchao Liu
- Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Chengcheng Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ran Tao
- Department of Organ Transplantation, Liaocheng People's Hospital, Liaocheng, China
| | - Bi Pan
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wei Liu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Di Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Hu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zeliang Xu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Dehong Tan
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yanjiao Ou
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xun Li
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yuemei You
- Department of Surgery and Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Yazdani HO, Yang R, Haykal T, Tohme C, Kaltenmeier C, Wang R, Nakano R, Nigmet Y, Gambella A, Loughran P, Hughes CB, Geller DA, Tohme S. Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model. Transplantation 2025; 109:161-173. [PMID: 39656524 DOI: 10.1097/tp.0000000000005176] [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: 08/24/2024]
Abstract
BACKGROUND Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation. METHODS Donor C57BL/6 mice underwent ExT via treadmill running or remained sedentary. After 4 wk, the donor liver underwent cold storage and subsequent orthotopic liver transplantation or ex vivo warm reperfusion. RESULTS Donor liver from mice subjected to ExT showed significantly decreased hepatic injury on reperfusion. Tissue histology revealed decreased sinusoidal congestion, vacuolization, and hepatocellular necrosis in livers from ExT mice, and immunofluorescence staining further revealed a decreased number of apoptotic cells in ExT grafts. Livers from ExT donors expressed decreased intragraft inflammatory cytokines cascade, decreased neutrophil infiltration and neutrophil extracellular traps, and increased M2 phenotype of recipient macrophages compared with grafts from sedentary mice. After cold storage, liver grafts from ExT donors showed decreased accumulation of reactive oxygen species and decreased levels of cytochrome c and high mobility group box 1 released in the liver effluent. In addition, ExT grafts showed upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and higher levels of mitochondrial content. Similar effects of decreased hepatic injury were observed in wild-type mice when pretreated with a PGC-1α stimulator ZLN005 instead of ExT. CONCLUSIONS These findings suggest that augmenting hepatocytic mitochondrial content through donor exercise or PGC-1α stimulation may offer therapeutic avenues to mitigate postreperfusion inflammation and improve transplant outcomes.
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Affiliation(s)
- Hamza O Yazdani
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
| | - Ruiqi Yang
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
- School of Medicine, Tsinghua University, Beijing, China
| | - Tony Haykal
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Celine Tohme
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Ronghua Wang
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Ryosuke Nakano
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Yermek Nigmet
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Alessandro Gambella
- Division of Liver and Transplant Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Patricia Loughran
- Department of Cell Biology, Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA
| | - Christopher B Hughes
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - David A Geller
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Samer Tohme
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
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Tang R, Wu G, Tong X, Yu L, Li A, Lin J, Xu G, Lu Q. A novel proceduralized donor liver back-table preparation technique minimizes hemorrhage following liver implantation in orthotropic liver transplantation. Front Surg 2024; 11:1356142. [PMID: 39726765 PMCID: PMC11669602 DOI: 10.3389/fsurg.2024.1356142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 11/18/2024] [Indexed: 12/28/2024] Open
Abstract
Background Intraoperative hemorrhage is one of the major complications of orthotopic liver transplantation (OLTX) and is mainly caused by technical difficulties of the surgical procedure besides primary liver diseases. The present study aimed to evaluate the feasibility and clinical effects of a novel proceduralized donor liver back-table preparation (DLBTP) technique for use in OLTX. Methods This retrospective study was conducted between January 2018 and June 2020 based on patients who had undergone OLTX. All livers transplanted using the reported back-table procedures were defined as the control group A (n = 43), while those prepared using our new procedure as the experimental group B (n = 160). The first-hand surgical experience of transplant surgeons was surveyed in a post hoc comparative analysis. Results DLBTP time was significantly longer and the probability of low-quality hepatic artery skeletonization was lower in group B compared to group A patients. Compared to group A, the time for hemorrhage control was shorter [P < 0.05, 0.3 h (range, 0.17-0.58 h)], and the degree of blood loss was less [P < 0.05, 60 ml (range, 30-240 ml)] in group B. Major bleeding sites were soft tissue of the hepatic hilum and the wall of the inferior vena cava. Due to trimmed soft tissue in the first porta hepatis region, there was less blood oozing, making it easier to stem the bleeding and construct anastomosis. Conclusion Although the procedural DLBTP for OLTX was time-consuming, the new procedure significantly reduced the degree of hemorrhage and the time required to control bleeding.
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Affiliation(s)
| | | | | | | | | | | | | | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing, China
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Tang LCY, Chetwood JD, Lai MSM, Yip TCF, Cao R, Powter E, Salimi S, Wu R, Coulshed A, Bowen DG, Strasser SI, Valliani T, Crawford M, Pulitano C, McKenzie C, Kench J, McCaughan GW, Liu K. Incidence, epidemiology, and outcomes of acute allograft rejection following liver transplantation in Australia. Liver Transpl 2024; 30:1039-1049. [PMID: 38647419 DOI: 10.1097/lvt.0000000000000375] [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: 09/25/2023] [Accepted: 03/30/2024] [Indexed: 04/25/2024]
Abstract
Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology, and outcomes of acute rejection have not been well described in Australia. We retrospectively studied consecutive adults who underwent deceased donor LT at a single center between 2010 and 2020. Donor and recipient data at the time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed, and only a graft's first instance of biopsy-proven acute rejection was analyzed. During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p =0.11). The median time to the first episode of rejection was 71 days after LT: 2.2% hyperacute, 50.4% early (≤90 d), and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI: 0.97-1.00, p =0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI: 1.27-5.09, p <0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI: 0.08-0.58, p <0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI: 2.21-4.42, p <0.001) and patient survival (aHR 3.42, 95% CI: 2.35-4.98, p <0.001). In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant, while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.
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Affiliation(s)
- Lauren C Y Tang
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - John D Chetwood
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Mandy S M Lai
- Department of Medicine and Therapeutics, Medical Data Analytic Centre, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Terry C F Yip
- Department of Medicine and Therapeutics, Medical Data Analytic Centre, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Rena Cao
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Elizabeth Powter
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Shirin Salimi
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Rodger Wu
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Andrew Coulshed
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - David G Bowen
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Simone I Strasser
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Talal Valliani
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Michael Crawford
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Carlo Pulitano
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Catriona McKenzie
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- New South Wales Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - James Kench
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- New South Wales Health Pathology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Geoffrey W McCaughan
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Liver Injury and Cancer Program, Centenary Institute, Sydney, New South Wales, Australia
| | - Ken Liu
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Liver Injury and Cancer Program, Centenary Institute, Sydney, New South Wales, Australia
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Isdahl M, Katz L, Johnson M, Leverson G, Al-Adra D, Thibeault S. Predictors for postoperative dysphagia in liver transplant recipients. FRONTIERS IN TRANSPLANTATION 2024; 3:1415141. [PMID: 39221171 PMCID: PMC11363258 DOI: 10.3389/frtra.2024.1415141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 07/23/2024] [Indexed: 09/04/2024]
Abstract
Introduction Liver transplant recipients are at a heightened risk for oropharyngeal dysphagia; identification of those who are at high risk for postoperative dysphagia could reduce hospital costs and length of stay. We sought to identify predictors of dysphagia, in a large cohort of patients who underwent liver transplantation. Methods Electronic medical records were queried for patients undergoing liver transplantation, who underwent instrumental swallowing evaluations. Demographics, functional outcomes, and interventions were collected. Logistic regression analyses were performed to identify predictors of dysphagia. Results Seven hundred and ninety-five patients met inclusionary criteria. Multivariate analyses found ethnic group (p = .0191), MELD Score (p < 0001), cold ischemia time (p = .0123), and length of intubation (p < .0001) to be predictors of post-operative development of dysphagia. Pre-transplant dialysis (p < .0001), dysphagia related to end stage liver disease (p < .0001), Karnofsky Performance Status Scale (p < .0001), wait time to transplant (p = 0.0173), surgery time (p = 0.0095), tracheostomy (p < 0.0001), and transfusion of intraoperative RBC (p < .0001), intraoperative platelets (p = 0.0018), intraoperative FFP (p = 0.0495), perioperative FFP (p = 0.0002), perioperative platelets (p = 0.0151) and perioperative RBC (p = 0.0002) were variables of significance associated with the development of postoperative dysphagia from univariate analysis. Conclusions Our results propose a set of predictors that should be considered when identifying post-operative critically ill patients at risk for dysphagia.
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Affiliation(s)
- Marian Isdahl
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
| | - Lily Katz
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
| | - Michaela Johnson
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
- Department of Brain and Spine, University of Tennessee Medical Center, Knoxville, TN, United States
| | - Glen Leverson
- Department of Surgery, University of Wisconsin Madison, Madison, WI, United States
| | - David Al-Adra
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Susan Thibeault
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
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Ximenes JLS, Rocha-Filho JA, Galvão FHF, Lanchotte C, Kubrusly MS, Leitão RMC, Jukemura J, Moscoso AV, Abdo EE, D’Albuquerque LAC, Figueira ERR. The Effect of Ascorbic Acid on Hepatic Ischaemia-Reperfusion Injury in Wistar Rats: An Experimental Study. Int J Mol Sci 2024; 25:8833. [PMID: 39201519 PMCID: PMC11354593 DOI: 10.3390/ijms25168833] [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: 06/25/2024] [Revised: 07/10/2024] [Accepted: 07/18/2024] [Indexed: 09/02/2024] Open
Abstract
Liver ischaemia-reperfusion (IR) during hepatic surgeries can lead to liver cell death via oxidative stress and the activation of immune cells, the release of cytokines, and damage-associated molecular patterns. Ascorbic acid has been shown to confer potential protective effects against IR injury, mainly due to its antioxidant properties. This study evaluated the effect of ascorbic acid infusion at different time points during hepatic IR in rats. Thirty-six male Wistar rats were divided into control and experimental groups that received the same total ascorbic acid dose at three different infusion times: before ischaemia, before reperfusion, or before both ischaemia and reperfusion. All of the animals experienced hepatic IR injury. We measured the hepatic enzymes, cytokines, and portal blood flow. Animals receiving ascorbic acid before both ischaemia and reperfusion had lower liver enzyme levels, reduced inflammation, and better portal venous flow than other animals. Divided doses of ascorbic acid before IR may be beneficial for reducing liver injury associated with IR.
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Affiliation(s)
- Jorge Luiz Saraiva Ximenes
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Disciplina de Anestesiologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | - Joel Avancini Rocha-Filho
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Disciplina de Anestesiologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | - Flavio Henrique Ferreira Galvão
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Serviço de Transplante de Fígado e Órgãos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | - Cinthia Lanchotte
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
| | - Marcia Saldanha Kubrusly
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
| | - Regina Maria Cubero Leitão
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
| | - Jose Jukemura
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | | | - Emilio Elias Abdo
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | - Luiz Augusto Carneiro D’Albuquerque
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Serviço de Transplante de Fígado e Órgãos do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
| | - Estela Regina Ramos Figueira
- Laboratório de Investigação Medica 37, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil; (J.L.S.X.); (J.A.R.-F.); (F.H.F.G.); (C.L.); (M.S.K.); (R.M.C.L.); (J.J.); (E.E.A.); (L.A.C.D.)
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, Brazil
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Risbey CWG, Lau NS, Niu A, Zhang WB, Crawford M, Pulitano C. Return of the cold: How hypothermic oxygenated machine perfusion is changing liver transplantation. Transplant Rev (Orlando) 2024; 38:100853. [PMID: 38581881 DOI: 10.1016/j.trre.2024.100853] [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: 03/04/2024] [Revised: 03/28/2024] [Accepted: 04/01/2024] [Indexed: 04/08/2024]
Abstract
Hypothermic Oxygenated machine PErfusion (HOPE) has recently emerged as a preservation technique which can reduce ischemic injury and improve clinical outcomes following liver transplantation. First developed with the advent solid organ transplantation techniques, hypothermic machine perfusion largely fell out of favour following the development of preservation solutions which can satisfactorily preserve grafts using the cheap and simple method, static cold storage (SCS). However, with an increasing need to develop techniques to reduce graft injury and better utilise marginal and donation after circulatory death (DCD) grafts, HOPE has emerged as a relatively simple and safe technique to optimise clinical outcomes following liver transplantation. Perfusing the graft with cold, acellular, oxygenated perfusate either via the portal vein (PV) alone, or via both the PV and hepatic artery (HA), HOPE is generally commenced for a period of 1-2 h immediately prior to implantation. The technique has been validated by multiple randomised control trials, and pre-clinical evidence suggests HOPE primarily reduces graft injury by decreasing the accumulation of harmful mitochondrial intermediates, and subsequently, the severity of post-reperfusion injury. HOPE can also facilitate real time graft assessment, most notably via the measurement of flavin mononucleotide (FMN) in the perfusate, allowing transplant teams to make better informed clinical decisions prior to transplantation. HOPE may also provide a platform to administer novel therapeutic agents to ex situ organs without risk of systemic side effects. As such, HOPE is uniquely positioned to revolutionise how liver transplantation is approached and facilitate optimised clinical outcomes for liver transplant recipients.
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Affiliation(s)
- Charles W G Risbey
- Department of Transplant Surgery, Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown 2050, NSW, Australia; Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital Transplant Institute (RPATI), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Central Clinical School, The University of Sydney, John Hopkins Dr, Camperdown 2050, NSW, Australia
| | - Ngee-Soon Lau
- Department of Transplant Surgery, Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown 2050, NSW, Australia; Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital Transplant Institute (RPATI), 145 Missenden Rd, Camperdown 2050, NSW, Australia
| | - Anita Niu
- Department of Transplant Surgery, Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown 2050, NSW, Australia; Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital Transplant Institute (RPATI), 145 Missenden Rd, Camperdown 2050, NSW, Australia
| | - Wesley B Zhang
- Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia
| | - Michael Crawford
- Department of Transplant Surgery, Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown 2050, NSW, Australia; Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital Transplant Institute (RPATI), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Central Clinical School, The University of Sydney, John Hopkins Dr, Camperdown 2050, NSW, Australia
| | - Carlo Pulitano
- Department of Transplant Surgery, Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown 2050, NSW, Australia; Centre for Organ Assessment, Repair, & Optimization (COARO), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Royal Prince Alfred Hospital Transplant Institute (RPATI), 145 Missenden Rd, Camperdown 2050, NSW, Australia; Central Clinical School, The University of Sydney, John Hopkins Dr, Camperdown 2050, NSW, Australia.
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9
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Anilir E, Sönmez Topçu F, Şahin E, Oral A, Ayyildiz Civan H, Orhan Poyrazoğlu K, Dirican A, Ünal B. Effects of Peroperative Cold Ischemia Time and Anhepatic Phase in Adult Living Donor Liver Transplant Recipients: Operation Time That is Not Affected by the Anhepatic Phase But is Prolonged by Cold Ischemia Time. Transplant Proc 2024; 56:1374-1377. [PMID: 39003204 DOI: 10.1016/j.transproceed.2024.02.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 01/25/2024] [Accepted: 02/16/2024] [Indexed: 07/15/2024]
Abstract
OBJECTIVE It was aimed to examine the overall role of cold ischemia time and anhepatic phase durations in terms of peroperative blood transfusion needs, hospital stay conditions and postoperative charges, and survival in recipients. MATERIAL AND METHODS One hundred forty-eight adult living donor liver transplant recipients (18 years and older) were included in the study. Whether the anhepatic phase and cold ischemia duration have an effect on the rates of surgery time, blood product transfusion, total hospital and intensive care unit stay, postoperative biliary complications, hepatic vein thrombosis, portal vein thrombosis, early postoperative bleeding, sepsis, and primary graft dysfunction. Was analyzed statistically. In addition, the effect of the anhepatic phase and cold ischemia time on graft survival was statistically examined by creating an average of the patient follow-up period. RESULTS It was observed that the operation time increased statistically as the cold ischemia time increased (P = .000). No statistically significant relationship was found between other findings and cold ischemia time and anhepatic phase. CONCLUSION Prolonged surgery time due to increased cold ischemia time may be an important finding in terms of peroperative and postoperative results of the graft.
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Affiliation(s)
- Ender Anilir
- Organ Transplantation Center, Biruni University Hospital, İstanbul, Türkiye.
| | - Feyza Sönmez Topçu
- Radiology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Emrah Şahin
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Alihan Oral
- İnternal Medicine Department, Fenerbahce University, Biruni University, İstanbul, Türkiye
| | - Hasret Ayyildiz Civan
- Pediatric Gastroenterology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Kürşat Orhan Poyrazoğlu
- Gastroenterology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Abuzer Dirican
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Bülent Ünal
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
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10
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Cesaretti M, Izzo A, Pellegrino RA, Galli A, Mavrothalassitis O. Cold ischemia time in liver transplantation: An overview. World J Hepatol 2024; 16:883-890. [PMID: 38948435 PMCID: PMC11212655 DOI: 10.4254/wjh.v16.i6.883] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/26/2024] [Accepted: 05/20/2024] [Indexed: 06/20/2024] Open
Abstract
The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.
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Affiliation(s)
- Manuela Cesaretti
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari 09122, Italy
- Department of Nanophysic, Istituto Italiano di Tecnologia, Genova 16163, Italy.
| | - Alessandro Izzo
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari 09122, Italy
| | | | - Alessandro Galli
- Department of Critical Care Medicine and Anesthesia, ASST Papa Giovanni XXIII, Bergamo 24100, Italy
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, United States
| | - Orestes Mavrothalassitis
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, United States
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11
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Krendl FJ, Cardini B, Laimer G, Singh J, Resch T, Oberhuber R, Schneeberger S. Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation. Transplantation 2024; 108:1410-1416. [PMID: 38548703 DOI: 10.1097/tp.0000000000004997] [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] [Indexed: 05/30/2024]
Abstract
BACKGROUND Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSIONS NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.
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Affiliation(s)
- Felix J Krendl
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Gregor Laimer
- Interventional Oncology/Stereotaxy and Robotics, Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Jessica Singh
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Center for Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria
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12
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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13
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Imaoka Y, Bozhilov KK, Bekki Y, Akabane M, Kwong AJ, Ohira M, Ohdan H, Esquivel CO, Melcher ML, Sasaki K. Breaking distance barriers in liver transplantation: Risk factors and outcomes of long-distance liver grafts. Surgery 2024; 175:513-521. [PMID: 37980203 DOI: 10.1016/j.surg.2023.09.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/28/2023] [Accepted: 09/26/2023] [Indexed: 11/20/2023]
Abstract
BACKGROUND Long-distance-traveling liver grafts in liver transplantation present challenges due to prolonged cold ischemic time and increased risk of ischemia-reperfusion injury. We identified long-distance-traveling liver graft donor and recipient characteristics and risk factors associated with long-distance-traveling liver graft use. METHODS We conducted a retrospective analysis of data from donor liver transplantation patients registered from 2014 to 2020 in the United Network for Organ Sharing registry database. Donor, recipient, and transplant factors of graft survival were compared between short-travel grafts and long-distance-traveling liver grafts (traveled >500 miles). RESULTS During the study period, 28,265 patients received a donation after brainstem death liver transplantation and 3,250 a donation after circulatory death liver transplantation. The long-distance-traveling liver graft rate was 6.2% in donation after brainstem death liver transplantation and 7.1% in donation after circulatory death liver transplantation. The 90-day graft survival rates were significantly worse for long-distance-traveling liver grafts (donation after brainstem death: 95.7% vs 94.5%, donation after circulatory death: 94.5% vs 93.9%). The 3-year graft survival rates were similar for long-distance-traveling liver grafts (donation after brainstem death: 85.5% vs 85.1%, donation after circulatory death: 81.0% vs 80.4%). Cubic spline regression analyses revealed that travel distance did not linearly worsen the prognosis of 3-year graft survival. On the other hand, younger donor age, lower donor body mass index, and shorter cold ischemic time mitigated the negative impact of 90-day graft survival in long-distance-traveling liver grafts. CONCLUSION The use of long-distance-traveling liver grafts negatively impacts 90-day graft survival but not 3-year graft survival. Moreover, long-distance-traveling liver grafts are more feasible with appropriate donor and recipient factors offsetting the extended cold ischemic time. Mechanical perfusion can improve long-distance-traveling liver graft use. Enhanced collaboration between organ procurement organizations and transplant centers and optimized transportation systems are essential for increasing long-distance-traveling liver graft use, ultimately expanding the donor pool.
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Affiliation(s)
- Yuki Imaoka
- Division of Abdominal Transplant, Stanford University School of Medicine, Stanford, CA; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | | | - Yuki Bekki
- Department of Surgery, Fukuoka City Hospital, Fukuoka, Japan
| | - Miho Akabane
- Division of Abdominal Transplant, Stanford University School of Medicine, Stanford, CA
| | - Allison J Kwong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Carlos O Esquivel
- Division of Abdominal Transplant, Stanford University School of Medicine, Stanford, CA
| | - Marc L Melcher
- Division of Abdominal Transplant, Stanford University School of Medicine, Stanford, CA
| | - Kazunari Sasaki
- Division of Abdominal Transplant, Stanford University School of Medicine, Stanford, CA.
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14
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Felli E, Felli E, Muttillo EM, Urade T, Laracca GG, Giannelli V, Famularo S, Geny B, Ettorre GM, Rombouts K, Pinzani M, Diana M, Gracia-Sancho J. Liver ischemia-reperfusion injury: From trigger loading to shot firing. Liver Transpl 2023; 29:1226-1233. [PMID: 37728488 DOI: 10.1097/lvt.0000000000000252] [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: 04/04/2023] [Accepted: 08/15/2023] [Indexed: 09/21/2023]
Abstract
An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.
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Affiliation(s)
- Eric Felli
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
| | - Emanuele Felli
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, France
| | - Edoardo M Muttillo
- Department of Medical Surgical Science and Translational Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Takeshi Urade
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Japan
| | - Giovanni G Laracca
- Department of Medical Surgical Science and Translational Medicine, Sant' Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Valerio Giannelli
- Department of Transplantation and General Surgery, San Camillo Hospital, Italy
| | - Simone Famularo
- Department of Biomedical Science, Humanitas University Pieve Emanuele, Italy
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
- Research Institute Against Cancer of the Digestive System (IRCAD), France
| | - Bernard Geny
- Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, France
| | - Giuseppe M Ettorre
- Department of Transplantation and General Surgery, San Camillo Hospital, Italy
| | - Krista Rombouts
- University College London - Institute for Liver and Digestive Health, Royal Free Hospital, NW3 2PF London, United Kingdom
| | - Massimo Pinzani
- University College London - Institute for Liver and Digestive Health, Royal Free Hospital, NW3 2PF London, United Kingdom
| | - Michele Diana
- Research Institute Against Cancer of the Digestive System (IRCAD), France
| | - Jordi Gracia-Sancho
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland
- Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, Hospital Clínic Barcelona, CIBEREHD, Barcelona, Spain
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15
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Anouti A, Patel MS, VanWagner LB, Lee WM, Fung JJ, Cholankeril G, Hwang CS, Mufti AR, Tujios S, Kerr T, Rich NE, Louissaint J, Desai DM, Vagefi PA, Hanish S, Shah J, Singal AG, Cotter TG. Biliary atresia and liver transplantation in the United States: A contemporary analysis. Liver Int 2023; 43:2198-2209. [PMID: 37548078 DOI: 10.1111/liv.15689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/29/2023] [Accepted: 07/24/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.
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Affiliation(s)
- Ahmad Anouti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Madhukar S Patel
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Lisa B VanWagner
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - John J Fung
- Department of Surgery, University of Chicago Medicine Transplant Institute, Chicago, Illinois, USA
| | - George Cholankeril
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Christine S Hwang
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Arjmand R Mufti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Shannan Tujios
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Thomas Kerr
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Nicole E Rich
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Jeremy Louissaint
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Dev M Desai
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Parsia A Vagefi
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Steven Hanish
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Jigesh Shah
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Thomas G Cotter
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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16
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Li T, Wu Y, Gong X, Che L, Sheng M, Jia L, Li H, Yu W, Weng Y. Risk factors for postreperfusion syndrome during living donor liver transplantation in paediatric patients with biliary atresia: a retrospective analysis. BMJ Paediatr Open 2023; 7:e001934. [PMID: 37407250 DOI: 10.1136/bmjpo-2023-001934] [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: 02/24/2023] [Accepted: 06/09/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND Living donor liver transplantation (LT) is the main treatment for paediatric biliary atresia (BA) in Asia. During LT, a series of haemodynamic changes often occur during LT reperfusion, which is called postreperfusion syndrome (PRS), and PRS is related to a prolonged postoperative hospital stay, delayed recovery of graft function and increased mortality. To reduce adverse reactions after paediatric living donor LT (LDLT), our study's objectives were to ascertain the incidence of PRS and analyse possible risk factors for PRS. METHODS With the approval of the Ethics Committee of our hospital, the clinical data of 304 paediatric patients who underwent LDLT from January 2020 to December 2021 were analysed retrospectively. According to the presence or absence of PRS, the paediatric patients were divided into the non-PRS group and the PRS group. Independent risk factors of PRS were analysed using logistic regression analysis. RESULTS PRS occurred in 132 recipients (43.4%). The peak values of AST (816 (507-1625) vs 678 (449-1107), p=0.016) and ALT (675 (415-1402) vs 545 (389-885), p=0.015) during the first 5 days after LDLT in paediatric patients with PRS were significantly higher than those in the non-PRS group. Meanwhile, the paediatric patients in the PRS group had longer intensive care unit stays and hospital stays, as well as lower 1-year survival rates. Graft cold ischaemic time (CIT) ≥90 min (OR (95% CI)=5.205 (3.094 to 8.754)) and a temperature <36°C immediately before reperfusion (OR (95% CI)=2.973 (1.669 to 5.295)) are independent risk factors for PRS. CONCLUSIONS The occurrence of hypothermia (<36.0℃) in children immediately before reperfusion and graft CIT≥90 min are independent risk factors for PRS. PRS was closely related to the postoperative adverse outcomes of paediatric patients.
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Affiliation(s)
- Tianying Li
- School of Medicine, Nankai University, Tianjin, China
| | - Yuli Wu
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Xinyuan Gong
- Department of Science and Education, Tianjin First Central Hospital, Tianjin, China
| | - Lu Che
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Mingwei Sheng
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Lili Jia
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Hongxia Li
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Wenli Yu
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
| | - Yiqi Weng
- Department of Anesthesiology, Tianjin First Central Hospital, Tianjin, China
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17
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Dery KJ, Yao S, Cheng B, Kupiec-Weglinski JW. New therapeutic concepts against ischemia-reperfusion injury in organ transplantation. Expert Rev Clin Immunol 2023; 19:1205-1224. [PMID: 37489289 PMCID: PMC10529400 DOI: 10.1080/1744666x.2023.2240516] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 07/20/2023] [Indexed: 07/26/2023]
Abstract
INTRODUCTION Ischemia-reperfusion injury (IRI) involves a positive amplification feedback loop that stimulates innate immune-driven tissue damage associated with organ procurement from deceased donors and during transplantation surgery. As our appreciation of its basic immune mechanisms has improved in recent years, translating putative biomarkers into therapeutic interventions in clinical transplantation remains challenging. AREAS COVERED This review presents advances in translational/clinical studies targeting immune responses to reactive oxygen species in IRI-stressed solid organ transplants, especially livers. Here we focus on novel concepts to rejuvenate suboptimal donor organs and improve transplant function using pharmacologic and machine perfusion (MP) strategies. Cellular damage induced by cold ischemia/warm reperfusion and the latest mechanistic insights into the microenvironment's role that leads to reperfusion-induced sterile inflammation is critically discussed. EXPERT OPINION Efforts to improve clinical outcomes and increase the donor organ pool will depend on improving donor management and our better appreciation of the complex mechanisms encompassing organ IRI that govern the innate-adaptive immune interface triggered in the peritransplant period and subsequent allo-Ag challenge. Computational techniques and deep machine learning incorporating the vast cellular and molecular mechanisms will predict which peri-transplant signals and immune interactions are essential for improving access to the long-term function of life-saving transplants.
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Affiliation(s)
- Kenneth J. Dery
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Siyuan Yao
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Brian Cheng
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jerzy W. Kupiec-Weglinski
- The Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation; David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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18
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Melandro F, Lai Q, Ghinolfi D, Manzia TM, Spoletini G, Rossi M, Agnes S, Tisone G, De Simone P. Outcome of liver transplantation in elderly patients: an Italian multicenter case-control study. Updates Surg 2023; 75:541-552. [PMID: 36814042 DOI: 10.1007/s13304-023-01448-0] [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: 05/07/2022] [Accepted: 02/03/2023] [Indexed: 02/24/2023]
Abstract
Despite the controversial results of liver transplantation (LT) in elderly recipients, the proportion of patients continues to increase. This study investigated the outcome of LT in elderly patients (≥ 65 years) in an Italian, multicenter cohort. Between January 2014 and December 2019, 693 eligible patients were transplanted, and two groups were compared: recipients ≥ 65 years (n = 174, 25.1%) versus 50-59 years (n = 519, 74.9%). Confounders were balanced using a stabilized inverse probability therapy weighting (IPTW). Elderly patients showed more frequent early allograft dysfunction (23.9 versus 16.8%, p = 0.04). Control patients had longer posttransplant hospital stays (median: 14 versus 13 days; p = 0.02), while no difference was observed for posttransplant complications (p = 0.20). At multivariable analysis, recipient age ≥ 65 years was an independent risk factor for patient death (HR 1.76; p = 0.002) and graft loss (HR 1.63; p = 0.005). The 3-month, 1-year, and 5-year patient survival rates were 82.6, 79.8, and 66.4% versus 91.1, 88.5, and 82.0% in the elderly and control group, respectively (log-rank p = 0.001). The 3-month, 1-year, and 5-year graft survival rates were 81.5, 78.7, and 66.0% versus 90.2, 87.2, and 79.9% in the elderly and control group, respectively (log-rank p = 0.003). Elderly patients with CIT > 420 min showed 3-month, 1-year, and 5-year patient survival rates of 75.7%, 72.8%, and 58.5% versus 90.4%, 86.5%, and 79.4% for controls (log-rank p = 0.001). LT in elderly (≥ 65 years) recipients provides favorable results, but inferior to those achieved in younger patients (50-59), especially when CIT > 7 h. Containment of cold ischemia time seems pivotal for favorable outcomes in this class of patients.
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Affiliation(s)
- Fabio Melandro
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy.
| | - Quirino Lai
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy
| | - Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Italy
| | - Tommaso Maria Manzia
- Hepatobiliary Surgery and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Massimo Rossi
- Sapienza University of Rome, AOU Umberto I Policlinico of Rome, Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giuseppe Tisone
- Hepatobiliary Surgery and Transplant Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy
| | - Paolo De Simone
- Department of Surgical, Medical, Biochemical Pathology and Intensive Care, University of Pisa, Pisa, Italy
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19
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Quaresima S, Mennini G, Manzia TM, Avolio AW, Angelico R, Spoletini G, Lai Q. The liver transplant surgeon Mondays blues: an Italian perspective. Updates Surg 2023; 75:531-539. [PMID: 35948742 PMCID: PMC10042950 DOI: 10.1007/s13304-022-01348-9] [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: 04/16/2022] [Accepted: 07/30/2022] [Indexed: 11/29/2022]
Abstract
Poor data exist on the influence of holidays and weekdays on the number and the results of liver transplantation (LT) in Italy. The study's main objective is to investigate the impact of holidays and the different days of the week on the LT number and early graft survival rates in a multi-centric Italian series. We performed a retrospective analysis on 1,026 adult patients undergoing first deceased-donor transplantation between January 2004 and December 2018 in the three university centers in Rome. During the 4,504 workdays, 881 LTs were performed (85.9%; one every 5.1 days on average). On the opposite, 145 LTs were done during the 975 holidays (14.1%; one every 7.1 days on average). Fewer LTs were performed on holidays (P = 0.004). There were no substantial differences in donor-, recipient- and transplant-related characteristics in LTs performed on weekdays or holidays. On Monday, fewer transplants were performed (vs. other weekdays: P < 0.0001; vs. Sunday: P = 0.03). At multivariable Cox regression analysis, LTs performed during the holiday or during the different days of the week were not found to be independent risk factors for the risk of 3- and 12-month graft loss. At three-month survival curves, no differences were observed among the transplants performed during the holidays versus the workdays (86.2 vs. 85.0%; P-0.70). The range of graft survival rates based on the day of the week was 81.6-86.9%, without showing any significant differences (P = 0.57). Fewer transplants are performed on holidays and Mondays. Survivals are not affected by holidays or the day the transplant is performed.
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Affiliation(s)
- Silvia Quaresima
- General Surgery and Organ Transplantation Unit, Department of General Surgery and Surgical Specialties, Sapienza University of Rome, AOU Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, Department of General Surgery and Surgical Specialties, Sapienza University of Rome, AOU Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy
| | - Tommaso M Manzia
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Alfonso W Avolio
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberta Angelico
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General Surgery and Surgical Specialties, Sapienza University of Rome, AOU Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.
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20
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Effects of Intensive Blood Glucose Control on Surgical Site Infection for Liver Transplant Recipients: A Randomized Controlled Trial. Transplant Proc 2023; 55:170-177. [PMID: 36567173 DOI: 10.1016/j.transproceed.2022.10.062] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/07/2022] [Accepted: 10/18/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND The evidence supporting intensive blood glucose control to prevent surgical site infections (SSIs) among liver transplant recipients is insufficient. We aimed to assess the effects of postoperative intensive blood glucose control (IBGC) against standard blood glucose control (SBGC) on the incidence of SSIs among adult liver transplant recipients. METHODS We performed a randomized controlled trial (ClinicalTrials.gov identifier NCT03474666). The IBGC target was 80 to 130 mg/dL, and the SBGC target was below 180 mg/dL. Analyses were made on an intention-to-treat basis. RESULTS Of the 41 recipients enrolled onto the trial, 20 were randomly allocated to the IBGC group and 21 to the SBGC group. There were no significant differences in SSIs among recipients allocated to either group (relative risk [RR], 0.78; 95% confidence interval [CI], 0.21-2.88; P = .69). Mean (SD) blood glucose levels were significantly lower in the IBGC group in the 24-hour period after surgery (145.0 [20.7] mg/dL and 230.2 [51.6] mg/dL; P = .001). While there were fewer episodes of hypoglycemia in the IBGC group, this was not statistically significant. There were no episodes of severe hypoglycemia in either group. Hyperglycemia and severe hyperglycemia were significantly more frequent in the SBGC group (RR, 0.70; 95% CI, 0.52-0.93; P = .001 and RR, 0.07; 95% CI, 0.01-0.48; P = .001, respectively). Length of hospital stay was significantly shorter for recipients in the IBGC group (13.1 [5.5] days vs 19.3 [12.1] days; P = .04). CONCLUSIONS Although this small trial did not find intensive control reduced SSI, it was associated with lower blood glucose levels, fewer episodes of hyperglycemia and severe hyperglycemia, and shorter length of hospital stay.
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21
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Predictors of Length of Stay and Mortality During Simultaneous Liver-Kidney Transplant Index Admission: Results From the US-Multicenter SLKT Consortium. Transplant Direct 2022; 8:e1408. [PMID: 36398193 PMCID: PMC9666195 DOI: 10.1097/txd.0000000000001408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/13/2022] [Accepted: 09/28/2022] [Indexed: 11/15/2022] Open
Abstract
Length of stay (LOS) during index solid organ transplant impacts morbidity and healthcare costs. To date, there are no studies evaluating characteristics and outcomes of simultaneous liver-kidney transplant (SLKT) index hospitalization. We examined factors associated with LOS and mortality during index SLKT admission. Methods Adult SLKT recipients between 2002 and 2017 at 6 transplant centers across 6 UNOS regions were retrospectively enrolled in the US-Multicenter SLKT Consortium. Multivariable regression analyses assessed predictors of SLKT LOS and death during index admission. Results Median age of cohort (N = 570) was 58 y (interquartile range: 51-64); 63% male, 75% White, 32.3% hepatitis C, 23.3% alcohol-related, 20.1% nonalcoholic steatohepatitis with median MELD-Na at SLKT 28 (23-34). Seventy-one percent were hospitalized at the time of SLKT with median LOS pretransplant of 10 d. Majority of patients were discharged alive (N = 549; 96%)' and 36% were discharged to subacute rehab facility. LOS for index SLKT was 19 d (Q1: 10, Q3: 34 d). Female sex (P = 0.003), Black race (P = 0.02), advanced age (P = 0.007), ICU admission at time of SLKT (P = 0.03), high MELD-Na (P = 0.003), on cyclosporine during index hospitalization (P = 0.03), pre-SLKT dialysis (P < 0.001), and kidney delayed graft function (P < 0.001) were the recipient factors associated with prolonged LOS during index SLKT hospitalization. Prolonged LOS also contributed to overall mortality (HR = 1.007; P = 0.03). Conclusions Despite excellent survival, index SLKT admission was associated with high-resource utilization with more than half the patients with LOS >2 wk and affected overall patient survival. Further investigation is needed to optimize healthcare resources for these patients in a financially strained healthcare landscape.
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22
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Koonmee S, Sangkhamanon S, Intarawichian P, Aphivatanasiri C, Kunprom W, Sa-Ngiamwibool P, Balthaisong S, Phuyao C, Prajumwongs P, Alaghehbandan R, Thanee M. The Impact of Pre-analytical Quality Initiatives on Cholangiocarcinoma Diagnostics in Thailand. Front Public Health 2022; 10:792847. [PMID: 35757604 PMCID: PMC9231639 DOI: 10.3389/fpubh.2022.792847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 05/06/2022] [Indexed: 11/21/2022] Open
Abstract
Cholangiocarcinoma (CCA) is the most prevalent malignancy in Thailand, with unfortunate late diagnosis and frequent metastatic disease outcomes. An accurate tissue diagnosis is the first and most important step in the treatment of CCA. Tissue quality and preservation during the pre-analytical phase play major roles in the proper histological evaluation and potential biomarker testing. This study evaluated the impact of using the “Cholangiocarcinoma Screening and Care Program (CASCAP)” container, as an innovative tool to address pre-analytical challenges faced by pathology laboratories in Thailand. This is a comparison study examining the quality of CCA specimens using the CASCAP container vs. the conventional method, using hematoxylin and eosin (H&E) and immunohistochemistry (IHC). CCA tissue quality using the CASCAP container significantly reduced artifact deposition while improving the cellular structure and nuclear and cytoplasmic morphologies. The immunohistochemical expression of cytokeratin 19 (CK19), a prognostic marker in CCA, significantly improved in the CASCAP container group in comparison with the conventional method. This innovation is proven to significantly enhance the CCA tissue quality diagnostics and prognostic biomarker testing, hence improving overall cancer care, diagnosis, and treatment in Thailand.
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Affiliation(s)
- Supinda Koonmee
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Sakkarn Sangkhamanon
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piyapharom Intarawichian
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chaiwat Aphivatanasiri
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Waritta Kunprom
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Prakasit Sa-Ngiamwibool
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Suwit Balthaisong
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chitsakul Phuyao
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Piya Prajumwongs
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Reza Alaghehbandan
- Department of Pathology, Faculty of Medicine, Royal Columbian Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Malinee Thanee
- Cholangiocarcinoma Screening and Care Program, Khon Kaen University, Khon Kaen, Thailand.,Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.,Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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23
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Salvage of a Right-extended Split Liver Graft Using Ex Situ Normothermic Machine Perfusion-A New Therapeutic Horizon. Transplantation 2022; 106:e320-e321. [PMID: 35616915 DOI: 10.1097/tp.0000000000004067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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24
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Dalzell C, Vargas PA, Soltys K, Dipaola F, Mazariegos G, Oberholzer J, Goldaracena N. Living Donor Liver Transplantation vs. Split Liver Transplantation Using Left Lateral Segment Grafts in Pediatric Recipients: An Analysis of the UNOS Database. Transpl Int 2022; 36:10437. [PMID: 35391900 PMCID: PMC8980223 DOI: 10.3389/ti.2022.10437] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/03/2022] [Indexed: 12/12/2022]
Abstract
Split and LDLT in pediatric patients have the potential to decrease wait times and waitlist mortality. Using UNOS-STAR data, we compared outcomes of pediatric patients undergoing LDLT and SLT using LLS grafts. The baseline characteristics and post-operative outcomes were compared between groups. Actuarial graft and patient survival were analyzed with Kaplan-Meier curves. Between 2010 and 2019, 911 pediatric LT were included in the analysis (LD graft group, n = 508, split graft group, n = 403). LD graft recipients spent more time on the waitlist vs. the split graft group (60 (22–138) days vs. 46 (16–108) days; p = 0.007). LD recipients had a lower rate of graft failure, found in 9.8% of patients compared with 14.6% in the split graft group (p = 0.02). HAT was the most common graft failure cause, with similar rates. Graft and patient survival at 1-, 3-, and 5-years was comparable between LDLT and SLT. In subgroup analyses, patients with biliary atresia, those ≤10 kg or ≤10 years old receiving an LD graft showed improved graft survival. In conclusion, LDLT is associated with a lower rate of graft failure in pediatric patients. The use of LLS regardless of the type of donor is a safe way to facilitate access to transplantation to pediatric patients with acceptable short and long-term outcomes.
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Affiliation(s)
- Christina Dalzell
- School of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Paola A Vargas
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA, United States
| | - Kyle Soltys
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA, United States.,Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Frank Dipaola
- Division of Pediatric Gastroenterology, Department of Pediatrics, University of Virginia, Charlottesville, VA, United States
| | - George Mazariegos
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA, United States.,Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Jose Oberholzer
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA, United States
| | - Nicolas Goldaracena
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA, United States
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25
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Yang M, Khan AR, Lu D, Wei X, Shu W, Xu C, Pan B, Zhou Z, Wang R, Wei Q, Cen B, Cai J, Zheng S, Xu X. Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation. Front Med (Lausanne) 2022; 9:772048. [PMID: 35308496 PMCID: PMC8927074 DOI: 10.3389/fmed.2022.772048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/26/2022] [Indexed: 11/24/2022] Open
Abstract
Background A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes. Method Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured. Results After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 μmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%. Conclusion The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.
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Affiliation(s)
- Mengfan Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Di Lu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Wenzhi Shu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Chuanshen Xu
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Binhua Pan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
| | - Rui Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Beini Cen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Jinzhen Cai
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Donor selection for multiorgan transplantation. Curr Opin Organ Transplant 2022; 27:52-56. [PMID: 34939964 DOI: 10.1097/mot.0000000000000940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW There is limited data and guidance on donor selection for multiorgan transplantation. In this article, we review the current Organ Procurement and Transplantation Network policy on multiorgan allocation and the ideal donor criteria for each specific organ, in order to provide a framework to guide donor selection for various scenarios of multiorgan transplantation, including heart-kidney, heart-lung, heart-liver and heart-kidney-liver transplant procedures. RECENT FINDINGS Combined heart-kidney transplantation is the most common multiorgan transplant procedure and requires the most stringent HLA matching to ensure optimal graft survival. Using the virtual crossmatch and desensitization therapies can shorten waitlist times without increasing posttransplant rejection or mortality rates. The ideal heart-lung donor tends to be younger than other multiorgan transplants, and more tolerant to HLA mismatch, but ideally requires donors with no prior history of smoking, a short period of time on mechanical ventilation, adequate oxygenation and absence of pulmonary infection. The ideal heart-liver donor is often driven by criteria specific to the donor heart. Finally, several observational studies suggest that livers are more tolerant to HLA mismatch than other organs, and offer some degree of immune protection in combined organ transplants. SUMMARY Multiorgan transplantation is a steadily growing field. The required short ischemic time for the donor heart is often the limiting factor, as well as the scarcity of appropriate donors available within geographical confines. In general, as with single organ transplantation, younger age, size matching, few medical comorbidities and HLA compatibility confer the best posttransplant outcomes.
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Du AL, Danforth DJ, Waterman RS, Gabriel RA. Is Obesity Associated With Better Liver Transplant Outcomes? A Retrospective Study of Hospital Length of Stay and Mortality Following Liver Transplantation. Anesth Analg 2022; 135:118-127. [PMID: 35061633 DOI: 10.1213/ane.0000000000005921] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Hong K, Hong SK, Han ES, Suh S, Hong SY, Lee JM, Choi Y, Yi NJ, Lee KW, Suh KS. Pure Laparoscopic vs. Open Right Hepatectomy in Living Liver Donors: Bench-Surgery Time. Front Surg 2021; 8:771026. [PMID: 34888346 PMCID: PMC8649712 DOI: 10.3389/fsurg.2021.771026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/02/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Recently, there have been several reports on pure laparoscopic donor right hepatectomy (PLDRH), but the effect of pure laparoscopy on bench surgery has not been evaluated. This study aimed to compare bench-surgery time between PLDRH and conventional donor right hepatectomy (CDRH). Methods: We retrospectively reviewed the medical records of 758 live liver donors between January 2012 and December 2019. We divided the patients into two groups: between January 2012 and September 2015, when we exclusively performed CDRH, and between March 2016 and December 2019, when PLDRH was standardized. We excluded all other types of graft donor hepatectomy, laparoscopic assisted donor hepatectomy, and cases with no recorded data. Results: In total, 267 donors were included in the PLDRH group and were compared with 247 donors in the CDRH group. Similar proportions of graft vascular variations were observed between the two groups. The mean bench-surgery time was longer in the PLDRH group than in the CDRH group (49.3 ± 19.9 vs. 39.5 ± 17.5 min; P < 0.001). Conclusion: The bench-surgery time was longer in the PLDRH group than the CDRH group, regardless of whether the vascular network was reconstructed. Expertise in bench-surgery as well as donor surgery and recipient surgery is mandatory for PLDRH to be safe and feasible.
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Affiliation(s)
- Kwangpyo Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.,Department of Surgery, Uijeongbu Eulji Medical Center, Uijeongbu, South Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Su Young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
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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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Guertin L, Earle M, Dardas T, Brown C. Post-Heart Transplant Care Pathway's Impact on Reducing Length of Stay. J Nurs Care Qual 2021; 36:350-354. [PMID: 33534348 DOI: 10.1097/ncq.0000000000000546] [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: 10/22/2022]
Abstract
BACKGROUND Prolonged length of stay (LOS) has undesirable consequences including increased cost, resource consumption, morbidity, and disruptions in hospital flow. LOCAL PROBLEM A high-volume heart transplant center in the Pacific Northwest had a mean index hospital LOS of 23 days, with a goal of 10 days according to the institutional heart transplant care pathway. METHODS A retrospective, regression analysis was used to identify the factors contributing to LOS of 41 post-heart transplant patients. INTERVENTIONS The post-heart transplant care pathway and order set were modified accordingly and reintroduced to the health care team. RESULTS Factors contributing to LOS included number of days (1) until the first therapeutic calcineurin inhibitor level, (2) until intravenous diuretics were no longer required, and (3) outside of a therapeutic calcineurin inhibitor range. The interventions reduced the mean LOS by 8 days. CONCLUSIONS Increased awareness of LOS, education, and consistent use of care pathways can significantly reduce length of stay.
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Affiliation(s)
- Lisa Guertin
- University of Washington Medical Center, Seattle (Ms Guertin and Dr Dardas); Rush University College of Nursing, Chicago, Illinois (Dr Earle); and Decision Patterns, Oakland, California (Dr Brown)
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Sáez de la Fuente I, Sáez de la Fuente J, Molina Collado Z, Chacón Alves S, Sánchez-Bayton Griffith M, Lesmes González de Aledo A, Barea Mendoza J, Sánchez-Izquierdo Riera JÁ, García de Lorenzo A, Montejo González JC. Combination of arterial lactate levels and Cv-aCO2/Da-vO2 ratio to predict early allograft dysfunction after liver transplantation. Clin Transplant 2021; 35:e14482. [PMID: 34545961 DOI: 10.1111/ctr.14482] [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: 05/25/2021] [Revised: 08/30/2021] [Accepted: 09/08/2021] [Indexed: 11/27/2022]
Abstract
PURPOSE We examined the ability of the P(v-a)CO2/Da-vO2 ratio combined with elevated lactate levels to predict early allograft dysfunction (EAD). MATERIALS AND METHODS Patients were classified into four groups according to lactate levels and P(v-a)CO2/Da-vO2 ratio: Group 1; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; Group 2; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0; group 3; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; group 4; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0. We defined EAD according to Olthoff criteria. RESULTS One-hundred and fifty patients were included. EAD occurred in 41 patients (27.3%), and was associated with worse graft survival at 1 year (92% vs. 73%; P = ,003) as well as a higher re-transplantation rate (4,6% vs. 17,1%; P = ,019). The multivariate analysis revealed that P(v-a)CO2/Da-vO2 ratio at T6 [OR 7.05(CI95% 2.77-19.01, P<.001)] was an independent predictor for EAD. Belonging to group 1 at 6 h was associated with worse clinical outcomes but no association was found with 1-year graft survival or 1-year patient survival. CONCLUSIONS In this single center, prospective, observational study in patients who received an OLT, we found that elevated lactate levels combined with a high Cv-aCO2/Da-vO2 after 6 h was associated with the development of EAD and worse clinical outcomes in the early postoperative period.
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Affiliation(s)
| | | | | | - Silvia Chacón Alves
- Hospital Universitario 12 de Octubre, Critical Care Department, Madrid, Spain
| | | | | | - Jesús Barea Mendoza
- Hospital Universitario 12 de Octubre, Critical Care Department, Madrid, Spain
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Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation. SENSORS 2021; 21:s21061993. [PMID: 33808978 PMCID: PMC8001362 DOI: 10.3390/s21061993] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/23/2022]
Abstract
Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.
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Factors Associated with Prolonged Recipient Hepatectomy Time During Liver Transplantation: A Single-Centre Experience. World J Surg 2021; 44:3486-3490. [PMID: 32566975 DOI: 10.1007/s00268-020-05643-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recipient hepatectomy during liver transplantation can be a challenging operation and can increase cold ischaemic time. The aim of this study is to assess factors associated with prolonged recipient hepatectomy. METHODS From 2005 to 2015, 930 patients were submitted to liver transplantation in our hospital. Prolonged hepatectomy time was defined as operative time >180 min (from knife on skin to total hepatectomy). Patients undergoing early liver retransplantation and living donation were excluded. RESULTS A total of 715 patients were included in our study. Median age at transplantation was 53 (18-70) years, and median BMI was 26.2 (16-40). Median hepatectomy time was 131 min. Prolonged hepatectomy time occurred in 89 (12.4%) patients. At univariate analysis, previous decompensated cirrhosis with variceal bleeding and/or ascites, higher BMI and previous abdominal surgery were associated with prolonged operating time. Higher surgeon experience and acute liver failure were associated with shorter hepatectomy time. At multivariate analysis, previous episodes of variceal bleeding (p = 0.027, OR 1.78), BMI > 27 (p = 0.01, OR 1.75), previous abdominal surgery (p = 0.04, OR 1.68) and surgeon experience (p = 0.007, OR 2.04) were independently associated with operating time. Prolonged hepatectomy time was significantly associated with cold and total ischaemic time and intraoperative bleeding (p < 0.001, p = 0.002 and p = 0.002, respectively). CONCLUSIONS Recipient BMI, previous episodes of variceal bleeding, previous abdominal surgery and surgeon experience are independently associated with hepatectomy duration. These factors can be helpful to identify those patients with potentially prolonged hepatectomy time, and therefore, strategies can be put in place to optimize outcomes in this group of patients.
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Moosburner S, Sauer IM, Förster F, Winklmann T, Gassner JMGV, Ritschl PV, Öllinger R, Pratschke J, Raschzok N. Early Allograft Dysfunction Increases Hospital Associated Costs After Liver Transplantation-A Propensity Score-Matched Analysis. Hepatol Commun 2021; 5:526-537. [PMID: 33681684 PMCID: PMC7917275 DOI: 10.1002/hep4.1651] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/07/2020] [Accepted: 11/05/2020] [Indexed: 12/16/2022] Open
Abstract
Concepts to ameliorate the continued mismatch between demand for liver allografts and supply include the acceptance of allografts that meet extended donor criteria (ECD). ECD grafts are generally associated with an increased rate of complications such as early allograft dysfunction (EAD). The costs of liver transplantation for the health care system with respect to specific risk factors remain unclear and are subject to change. We analyzed 317 liver transplant recipients from 2013 to 2018 for outcome after liver transplantation and hospital costs in a German transplant center. In our study period, 1-year survival after transplantation was 80.1% (95% confidence interval: 75.8%-84.6%) and median hospital stay was 33 days (interquartile rage: 24), with mean hospital costs of €115,924 (SD €113,347). There was a positive correlation between costs and laboratory Model for End-Stage Liver Disease score (rs = 0.48, P < 0.001), and the development of EAD increased hospital costs by €26,229. ECD grafts were not associated with a higher risk of EAD in our cohort. When adjusting for recipient-associated risk factors such as laboratory Model for End-Stage Liver Disease score, recipient age, and split liver transplantation with propensity score matching, only EAD and cold ischemia increased total costs. Conclusion: Our data show that EAD leads to significantly higher hospital costs for liver transplantation, which are primarily attributed to recipient health status. Strategies to reduce the incidence of EAD are needed to control costs in liver transplantation.
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Affiliation(s)
- Simon Moosburner
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Igor M Sauer
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Frank Förster
- Corporate ControllingCharité-Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Thomas Winklmann
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Joseph Maria George Vernon Gassner
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Paul V Ritschl
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Robert Öllinger
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Johann Pratschke
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
| | - Nathanael Raschzok
- Department of SurgeryCharité-Universitätsmedizin BerlinCampus Charité MitteCampus Virchow-KlinikumCorporate Member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany
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35
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Strategies to Improve Liver Allocation, Distribution, and Utilization in a Broader Sharing Climate. CURRENT TRANSPLANTATION REPORTS 2021. [DOI: 10.1007/s40472-021-00316-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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36
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Micó-Carnero M, Rojano-Alfonso C, Álvarez-Mercado AI, Gracia-Sancho J, Casillas-Ramírez A, Peralta C. Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery. Int J Mol Sci 2020; 22:E44. [PMID: 33375200 PMCID: PMC7793124 DOI: 10.3390/ijms22010044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/18/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022] Open
Abstract
Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut-liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.
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Affiliation(s)
- Marc Micó-Carnero
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Carlos Rojano-Alfonso
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
| | - Ana Isabel Álvarez-Mercado
- Departamento de Bioquímica y Biología Molecular II, Escuela de Farmacia, Universidad de Granada, 18071 Granada, Spain;
- Institut of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria ibs, GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory IDIBAPS, 03036 Barcelona, Spain;
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain
| | - Araní Casillas-Ramírez
- Hospital Regional de Alta Especialidad de Ciudad Victoria “Bicentenario 2010”, Ciudad Victoria 87087, Mexico;
- Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros 87300, Mexico
| | - Carmen Peralta
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; (M.M.-C.); (C.R.-A.)
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Ünlü S, Lachmann N, Jara M, Ritschl PV, Wiering L, Eurich D, Denecke C, Biebl M, Chopra S, Gül-Klein S, Schöning W, Schmelzle M, Reinke P, Tacke F, Pratschke J, Öllinger R, Dziodzio T. Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation. J Clin Med 2020; 9:jcm9123986. [PMID: 33317012 PMCID: PMC7763868 DOI: 10.3390/jcm9123986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 11/30/2020] [Accepted: 12/07/2020] [Indexed: 02/07/2023] Open
Abstract
Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.
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Affiliation(s)
- Sinem Ünlü
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
- Institute for Transfusion Medicine, H&I Laboratory, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Nils Lachmann
- Institute for Transfusion Medicine, H&I Laboratory, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Maximilian Jara
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Paul Viktor Ritschl
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
- BIH Charité Clinician Scientist Program, Berlin Institute of Health (BIH), 10178 Berlin, Germany
| | - Leke Wiering
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Dennis Eurich
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Christian Denecke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Matthias Biebl
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Sascha Chopra
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Safak Gül-Klein
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Wenzel Schöning
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Petra Reinke
- Department of Nephrology and Internal Intensive Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Robert Öllinger
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
| | - Tomasz Dziodzio
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (S.Ü.); (M.J.); (P.V.R.); (L.W.); (D.E.); (C.D.); (M.B.); (S.C.); (S.G.-K.); (W.S.); (M.S.); (J.P.); (R.Ö.)
- Correspondence: ; Tel.: +48-(030)-450552001
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Hong SK, Yi NJ, Yoon KC, Kim MS, Lee JG, Lee S, Kang KJ, Hwang S, Ryu JH, Hong K, Han ES, Lee JM, Lee KW, Suh KS. Outcomes of Pediatric Liver Transplantation in Korea Using Two National Registries. J Clin Med 2020; 9:3435. [PMID: 33114650 PMCID: PMC7694033 DOI: 10.3390/jcm9113435] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/22/2020] [Accepted: 10/23/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND This retrospective study aimed to evaluate overall survival and the risk factors for mortality among Korean pediatric liver transplantation (LT) patients using data from two national registries: the Korean Network Organ Sharing (KONOS) of the Korea Centers for Disease Control and Prevention and the Korean Organ Transplantation Registry (KOTRY). METHODS Prospectively collected data of 755 pediatric patients who underwent primary LT (KONOS, February 2000 to December 2015; KOTRY, May 2014 to December 2017) were retrospectively reviewed. RESULTS The 1-, 5-, 10-, and 15-year survival rates were 90.6%, 86.7%, 85.8%, and 85.5%, respectively, in KONOS, and the 1-month, 3-month, 1-year, and 2-year survival rates were 92.1%, 89.4%, 89.4%, and 87.2%, respectively, in KOTRY. There was no significant difference in survival between the two registries. Multivariate analysis identified that body weight ≥6 kg (p <0.001), biliary atresia as underlying liver disease (p = 0.001), and high-volume center (p < 0.001) were associated with better survival according to the KONOS database, while hepatic artery complication (p < 0.001) was associated with poorer overall survival rates according to the KOTRY database. CONCLUSION Long-term pediatric patient survival after LT was satisfactory in this Korean national registry analysis. However, children with risk factors for poor outcomes should be carefully managed after LT.
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Affiliation(s)
- Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Kyung Chul Yoon
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (M.S.K.); (J.G.L.)
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea; (M.S.K.); (J.G.L.)
| | - Sanghoon Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 13557, Korea;
| | - Koo Jeong Kang
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu 42601, Korea;
| | - Shin Hwang
- Department of Surgery, College of Medicine University of Ulsan, Asan Medical Center, Seoul 05505, Korea;
| | - Je Ho Ryu
- Department of Surgery, Pusan National University School of Medicine, Pusan National University Yangsan Hospital, Yangsan 46241, Korea;
| | - Kwangpyo Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Eui Soo Han
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul 08826, Korea; (S.K.H.); (K.C.Y.); (K.H.); (E.S.H.); (J.-M.L.); (K.-W.L.); (K.-S.S.)
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Poor outcomes of early recurrent post-transplant bloodstream infection in living-donor liver transplant recipients. Eur J Clin Microbiol Infect Dis 2020; 40:771-778. [PMID: 33089389 PMCID: PMC7577647 DOI: 10.1007/s10096-020-04074-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 10/14/2020] [Indexed: 12/05/2022]
Abstract
Bloodstream infection (BSI) is a common complication after living-donor liver transplantation (LDLT). Some patients develop recurrent BSIs. We evaluated the impacts of early recurrent BSIs (ER-BSIs) on outcomes in LDLT recipients. LDLT cases between 2008 and 2016 were included. Early BSI (E-BSI) was defined as a BSI event that occurred within 2 months after LDLT. ER-BSIs were defined as new-onset BSIs within 2 months due to another pathogen at a ≥ 48-h interval or a relapse of BSIs by the same pathogen at a ≥ 1-week interval, with negative cultures in between. The primary objective was evaluating the all-cause mortality of each group of LDLT recipients (90 days and 1 year). The secondary objectives were analyzing associated factors of each all-cause mortality and risk factors for early single BSI and ER-BSI. Among 727 LDLT recipients, 108 patients experienced 149 events of E-BSI with 170 isolated pathogens. Twenty-eight patients (25.9%, 28/108) experienced ER-BSI. The 1-year survival rates of patients without BSI, with early single BSI event, and with ER-BSIs were 92.4%, 81.3%, and 28.6%, respectively. ER-BSI was the most significant risk factor for 1-year mortality (adjusted HR = 5.31; 95% CI = 2.27–12.40). Intra-abdominal and/or biliary complications and early allograft dysfunction were risk factors for both early single BSI and ER-BSI. Interestingly, longer cold ischemic time and recipient operative time were associated with ER-BSI. LDLT recipients with ER-BSI showed very low survival rates accompanied by intra-abdominal complications. Clinicians should prevent BSI recurrence by being aware of intra-abdominal complications.
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Wallace D, Cowling T, McPhail MJ, Brown SE, Aluvihare V, Suddle A, Auzinger G, Heneghan MA, Rowe IA, Walker K, Heaton N, van der Meulen J, Bernal W. Assessing the Time-Dependent Impact of Performance Status on Outcomes After Liver Transplantation. Hepatology 2020; 72:1341-1352. [PMID: 31968130 DOI: 10.1002/hep.31124] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 12/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period ("epoch") after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non-HCC recipients. APPROACH AND RESULTS We assessed pre-LT PS using the 5-point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow-up (0-90 days and 90 days to 1 year) and in different eras of transplantation (1995-2005 and 2006-2016). 2107 HCC and 10,693 non-HCC patients were included. One-year survival decreased with worsening PS in non-HCC recipients where 1-year survival was 91.9% (95% confidence interval [CI], 88.3-94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7-80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4-93.2) and 83.1% (95% CI, 61.0-93.3), respectively. Reduction in survival in non-HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post-LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40-0.74) and non-HCC recipients (0.48; 95% CI, 0.42-0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively). CONCLUSIONS Impact on mortality of the recipient's pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non-HCC recipients and across the full range of PS.
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Affiliation(s)
- David Wallace
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.,Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Thomas Cowling
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Mark J McPhail
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Sarah E Brown
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Varuna Aluvihare
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Abid Suddle
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Georg Auzinger
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Ian A Rowe
- Liver Unit, St James' Hospital and University of Leeds, Leeds, United Kingdom.,Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom
| | - Kate Walker
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Jan van der Meulen
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - William Bernal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
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Saeb-Parsy K, Martin JL, Summers DM, Watson CJE, Krieg T, Murphy MP. Mitochondria as Therapeutic Targets in Transplantation. Trends Mol Med 2020; 27:185-198. [PMID: 32952044 DOI: 10.1016/j.molmed.2020.08.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/09/2020] [Accepted: 08/03/2020] [Indexed: 12/23/2022]
Abstract
Advances in surgical procedures, technology, and immune suppression have transformed organ transplantation. However, the metabolic changes that occur during organ retrieval, storage, and implantation have been relatively neglected since the developments many decades ago of cold storage organ preservation solutions. In this review we discuss how the metabolic changes that occur within the organ during transplantation, particularly those associated with mitochondria, may contribute to the outcome. We show how a better understanding of these processes can lead to changes in surgical practice and the development of new drug classes to improve the function and longevity of transplanted grafts, while increasing the pool of organs available for transplantation.
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Affiliation(s)
- Kourosh Saeb-Parsy
- Department of Surgery and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, Biomedical Campus, University of Cambridge, Cambridge, CB2 2QQ, UK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge Biomedical Campus, Cambridge, UK
| | - Jack L Martin
- Department of Surgery and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, Biomedical Campus, University of Cambridge, Cambridge, CB2 2QQ, UK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge Biomedical Campus, Cambridge, UK
| | - Dominic M Summers
- Department of Surgery and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, Biomedical Campus, University of Cambridge, Cambridge, CB2 2QQ, UK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge Biomedical Campus, Cambridge, UK
| | - Christopher J E Watson
- Department of Surgery and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre, Biomedical Campus, University of Cambridge, Cambridge, CB2 2QQ, UK; NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge Biomedical Campus, Cambridge, UK
| | - Thomas Krieg
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Michael P Murphy
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK; Medical Research Council (MRC) Mitochondrial Biology Unit, Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK.
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Wallace D, Robb M, Hughes W, Johnson R, Ploeg R, Neuberger J, Forsythe J, Cacciola R. Outcomes of Patients Suspended From the National Kidney Transplant Waiting List in the United Kingdom Between 2000 and 2010. Transplantation 2020; 104:1654-1661. [PMID: 32732844 DOI: 10.1097/tp.0000000000003033] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND In the United Kingdom, 1 in 3 patients on the National Kidney Transplant Waiting List (NKTWL) is suspended from the list at least once during their wait. The mortality of this large cohort of patients remains underreported and poorly described. METHODS We linked patient records from the UK transplant registry to mortality data from the Office of National Statistics and evaluated the impact of a clinically induced suspension event by estimating hazard ratios (HRs) that compared mortality and graft survival between those who had experienced a suspension event and those who had not. RESULTS Between January 1, 2000, and December 31, 2010, 16.7% (2221/13 322) of all patients registered on the NKTWL were suspended. Forty-eight percent (588/1225) of those who were suspended and who were never transplanted died, most often from cardiothoracic causes. A suspension event was associated with increased mortality from the time of listing (adjusted HR [aHR], 1.79; 1.64-1.95) and from the time of transplantation (aHR, 1.20; 1.06-1.37; P = 0.005). Graft survival was also poorer in those who had been suspended (aHR, 1.13; 1.01-1.28; P = 0.04). CONCLUSIONS Patients suspended on the NKTWL have a significantly higher rate of mortality both on the waiting list and following transplantation. Earlier prioritization of patients at risk of experiencing a suspension event may improve their outcomes.
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Affiliation(s)
- David Wallace
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Matthew Robb
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Winter Hughes
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Rachel Johnson
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - Rutger Ploeg
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - James Neuberger
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
| | - John Forsythe
- Statistics and Clinical Studies, NHS Blood and Transplant, Bristol, United Kingdom
- Transplant Unit, University of Edinburgh, Edinburgh, United Kingdom
| | - Roberto Cacciola
- Department of Surgical Sciences, Transplant Unit, Tor Vergata University, Rome, Italy
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Núñez K, Hamed M, Fort D, Bruce D, Thevenot P, Cohen A. Links between donor macrosteatosis, interleukin-33 and complement after liver transplantation. World J Transplant 2020; 10:117-128. [PMID: 32864357 PMCID: PMC7428792 DOI: 10.5500/wjt.v10.i5.117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/07/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND As prevalence of nonalcoholic fatty liver disease increases in the population, livers with steatosis will continue to infiltrate the donor pool. Safe utilization of these extended criteria grafts is paramount given the increased risk associated with their use in transplantation. Prognostic factors that can predict liver dysfunction immediately after transplantation with macrosteatotic grafts are lacking. AIM To understand the relationship between interleukin-33 (IL-33) and complement in recipients immediately following liver reperfusion as a marker of liver dysfunction. METHODS Cohort consisted of patients who received a liver transplant from September 2016-September 2019 at our institution. Clinical variables were retrospectively extracted from the electronic medical record. Back-table donor biopsies were obtained with donor steatosis percentage retrospectively determined by a board-certified pathologist. Blood samples were available immediately following liver transplantation. Quantification of plasma IL-33 and complement proteins, C3a and C5a, were determined by enzyme-linked immunosorbent assay. For mRNA expression, RNA was extracted from donor biopsies and used against a 780 gene panel. RESULTS Cohort consisted of 99 donor and recipients. Donor median age was 45 years and 55% male. Recipients had a median age of 59 years with 62% male. The main etiologies were alcoholic hepatitis, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Median MELD-Na at transplant was 21. Donors were grouped based on moderate macrosteatosis (≥ 30%). Recipients implanted with moderate macrosteatotic grafts had significantly higher peak alanine aminotransferase/aspartate aminotransferase (P < 0.001 and P < 0.004), and increased incidence of early allograft dysfunction (60% compared to 18%). Circulating IL-33 levels were significantly elevated in recipients of ≥ 30% macrosteatotic grafts (P < 0.05). Recipients with detectable levels of circulating IL-33 immediately following reperfusion had significantly higher alanine aminotransferase/aspartate aminotransferase (P < 0.05 and P < 0.01). Activated complement (C3a and C5a) were elevated in recipients implanted with moderate macrosteatotic grafts. RNA expression analysis of donor biopsies revealed moderate steatotic grafts upregulated genes inflammatory processes while downregulated hepatocyte-produced complement factors. CONCLUSION Circulating IL-33 and activated complement levels immediately following liver reperfusion in recipients of moderate macrosteatotic grafts may identify which patients are at risk of early allograft dysfunction.
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Affiliation(s)
- Kelley Núñez
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - Mohammad Hamed
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - Daniel Fort
- Center for Outcomes and Health Services Research, Research Administration, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - David Bruce
- Multi-Organ Transplant Program, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - Paul Thevenot
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
| | - Ari Cohen
- Multi-Organ Transplant Program, Ochsner Clinic Foundation, New Orleans, LA 70121, United States
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de Vries RJ, Tessier SN, Banik PD, Nagpal S, Cronin SEJ, Ozer S, Hafiz EOA, van Gulik TM, Yarmush ML, Markmann JF, Toner M, Yeh H, Uygun K. Subzero non-frozen preservation of human livers in the supercooled state. Nat Protoc 2020; 15:2024-2040. [PMID: 32433625 DOI: 10.1038/s41596-020-0319-3] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 03/10/2020] [Indexed: 12/20/2022]
Abstract
Preservation of human organs at subzero temperatures has been an elusive goal for decades. The major complication hindering successful subzero preservation is the formation of ice at temperatures below freezing. Supercooling, or subzero non-freezing, preservation completely avoids ice formation at subzero temperatures. We previously showed that rat livers can be viably preserved three times longer by supercooling as compared to hypothermic preservation at +4 °C. Scalability of supercooling preservation to human organs was intrinsically limited because of volume-dependent stochastic ice formation at subzero temperatures. However, we recently adapted the rat preservation approach so it could be applied to larger organs. Here, we describe a supercooling protocol that averts freezing of human livers by minimizing air-liquid interfaces as favorable sites of ice nucleation and uses preconditioning with cryoprotective agents to depress the freezing point of the liver tissue. Human livers are homogeneously preconditioned during multiple machine perfusion stages at different temperatures. Including preparation, the protocol takes 31 h to complete. Using this protocol, human livers can be stored free of ice at -4 °C, which substantially extends the ex vivo life of the organ. To our knowledge, this is the first detailed protocol describing how to perform subzero preservation of human organs.
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Affiliation(s)
- Reinier J de Vries
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Surgery, Amsterdam University Medical Centers-location AMC, University of Amsterdam, Amsterdam, the Netherlands.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Shannon N Tessier
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Peony D Banik
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Sonal Nagpal
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Stephanie E J Cronin
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Sinan Ozer
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Ehab O A Hafiz
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA.,Department of Electron Microscopy Research, Theodor Bilharz Research Institute, Giza, Egypt
| | - Thomas M van Gulik
- Department of Surgery, Amsterdam University Medical Centers-location AMC, University of Amsterdam, Amsterdam, the Netherlands
| | - Martin L Yarmush
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - James F Markmann
- Center for Transplant Sciences, Massachusetts General Hospital, Boston, MA, USA
| | - Mehmet Toner
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA.,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA
| | - Heidi Yeh
- Center for Transplant Sciences, Massachusetts General Hospital, Boston, MA, USA
| | - Korkut Uygun
- Center for Engineering in Medicine, Harvard Medical School & Massachusetts General Hospital, Boston, MA, USA. .,Department of Research, Shriners Hospitals for Children-Boston, Boston, MA, USA.
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45
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Madreseh E, Mahmoudi M, Nassiri-Toosi M, Baghfalaki T, Zeraati H. Post Liver Transplantation Survival and Related Prognostic Factors among Adult Recipients in Tehran Liver Transplant Center; 2002-2019. ARCHIVES OF IRANIAN MEDICINE 2020; 23:326-334. [PMID: 32383617 DOI: 10.34172/aim.2020.22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 01/26/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Liver transplantation is a standard treatment for patients with end-stage liver disease (ESLD). However, with increasing demand for this treatment and limited resources, it is available only to patients who are more likely to survive. The primary aim was to determine prognostic factors for survival. METHODS We collected data from 597 adult patients with ESLD, who received a single organ and initial orthotopic liver transplantation (OLT) in our center between 20 March 2008 and 20 March 2018. In this historical cohort study, univariate and multiple Cox model were used to determine prognostic factors of survival after transplantation. RESULTS After a median follow-up of 825 (0-3889) days, 111 (19%) patients died. Survival rates were 88%, 85%, 82% and 79% at 90 days, 1 year, 3 years, and 5 years, respectively. Older patients (HR = 1.27; 95% CI: 1.01-1.59), presence of pre-OLT ascites (HR = 2.03; 95% CI: 1.16-3.57), pre-OLT hospitalization (HR = 1.88; 95% CI:1.02-3.46), longer operative time (HR = 1.006; 95% CI: 1.004-1.008), post-OLT dialysis (HR = 3.51; 95% CI: 2.07-5.94), cancer (HR = 2.69; 95% CI: 1.23-5.89) and AID (HR = 2.04; 95% CI: 1.17-3.56) as underlying disease versus hepatitis, and higher pre-OLT creatinine (HR = 1.67; 95% CI: 1.10-2.52) were associated with decreased survival. CONCLUSION In this center, not only are survival outcomes excellent, but also younger patients, cases with better pre-operative health conditions, and those without complications after OLT have superior survival.
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Affiliation(s)
- Elham Madreseh
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahmood Mahmoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohssen Nassiri-Toosi
- Liver Transplantation Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Taban Baghfalaki
- Department of Statistics, Faculty of Mathematics sciences, Tarbiat Modares University, Tehran, Iran
| | - Hojjat Zeraati
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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46
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Influence of Preformed Antibodies in Liver Transplantation. J Clin Med 2020; 9:jcm9030708. [PMID: 32151032 PMCID: PMC7141359 DOI: 10.3390/jcm9030708] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 03/02/2020] [Indexed: 12/12/2022] Open
Abstract
The significance of human leukocyte antigen (HLA) matching and preformed donor-specific antibodies (DSAs) in liver transplantation remains unclear. The aim of this study was to analyze the presence of DSAs in a large cohort of 810 liver recipients undergoing liver transplant to determine the influence on acute (AR) or chronic liver rejection (CR), graft loss and allograft survival. DSAs were identified using complement dependent cytotoxicity crossmatch (CDC-CM) and multiplexed solid-phase-based flow cytometry assay (Luminex). CDC-CM showed that a 3.2% of liver transplants were positive (+CDC-CM) with an AR frequency of 19.2% which was not different from that observed in negative patients (-CDC-CM, 22.3%). Only two patients transplanted with +CDC-CM (7.6%) developed CR and suffered re-transplant. +CDC-CM patients showed a significantly lower survival rate compared to -CDC-CM patients (23.1% vs. 59.1%, p = 0.0003), developing allograft failure within the first three months (p < 0.00001). In conclusion, we have demonstrated a relationship between the presence of preformed DSAs and the low graft liver survival, indicating the important role and the potential interest of performing this analysis before liver transplantation. Our results could help to detect patients with an increased risk of graft loss, a better choice of liver receptors as well as the establishment of individualized immunosuppressive regimens.
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47
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Sha M, Jeong S, Xia Q. Does Donor Allograft Microsteatosis Matter? Comparison of Outcomes in Liver Transplantation With a Propensity-Matched Cohort. Liver Transpl 2019; 25:1723-1724. [PMID: 31424625 DOI: 10.1002/lt.25624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 08/13/2019] [Indexed: 01/13/2023]
Affiliation(s)
- Meng Sha
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Seogsong Jeong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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48
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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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49
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Assessing the Impact of Suboptimal Donor Characteristics on Mortality After Liver Transplantation: A Time-dependent Analysis Comparing HCC With Non-HCC Patients. Transplantation 2019; 103:e89-e98. [DOI: 10.1097/tp.0000000000002559] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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50
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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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