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Kupiec-Weglinski JW. Ronald W. Busuttil, M.D., Ph.D.- TTS 2024 Medawar Prize Laureate. FRONTIERS IN TRANSPLANTATION 2025; 3:1530925. [PMID: 39911282 PMCID: PMC11796472 DOI: 10.3389/frtra.2024.1530925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 12/12/2024] [Indexed: 02/07/2025]
Abstract
The Transplantation Society (TTS) has been presenting the Medawar Prize at its biennial Congresses since 1990 in recognition of Sir Peter Medawar's seminal contributions to organ transplantation. This prestigious award acknowledges individuals for their outstanding accomplishments in experimental and clinical transplantation. On September 25, 2024, I was honored to introduce Ronald W. Busuttil, M.D., Ph.D., as the 2024 Medawar Prize Laureate during the 30th TTS Congress in Istanbul, Turkey. This article highlights the remarkable achievements and critical milestones in Dr. Busuttil's over 40-year career in organ transplantation, which have profoundly advanced scientific knowledge and clinical practice, embodying the true spirit of this accolade.
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Affiliation(s)
- 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, United States
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Liao M, Zhang H, Jin J, Guo H, Yi S, Ren J. Contrast-Enhanced Ultrasonography Findings Within 3 Days Postoperatively Are Associated With 1-Month Graft Failure After Split Liver Transplantation. Acad Radiol 2025; 32:180-190. [PMID: 39227218 DOI: 10.1016/j.acra.2024.07.024] [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: 04/07/2024] [Revised: 07/07/2024] [Accepted: 07/15/2024] [Indexed: 09/05/2024]
Abstract
RATIONALE AND OBJECTIVES This study aimed to evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) within 3 days postoperative can identify 1-month graft failure after split liver transplantation (SLT). MATERIALS AND METHODS A total of 58 consecutive patients who underwent SLT between February 2022 and September 2023 were included. The DUS and CEUS images and parameters within 3 days postoperatively were analyzed and recorded. The DUS parameters included peak systolic velocity (PSV), resistive index, and systolic acceleration time for the hepatic artery and PSV for the portal vein and hepatic vein. The CEUS qualitative analysis variables included the liver parenchyma enhancement pattern and the posterior enhancement attenuation. Logistic regression and Cox proportional hazard regression were used to evaluate the relationship between DUS/CEUS findings and 1-month graft failure. RESULTS Seven of the 58 liver grafts failed within 1 month. Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was observed in five of seven patients (71.4%) of graft failure, whereas good contrast enhancement (pattern Ⅰ) was found in 47 of the 51 patients (92.1%) in the successful group on postoperative day 3. Multivariate logistic regression analysis revealed that 1-month graft failure was independently predicted by operative time (odds ratio [OR] = 3.79, 95% confidence interval [CI]: 1.27-11.29, p = .017) and CEUS enhancement pattern on postoperative day 3 (OR = 90.88, 95% CI: 2.77-2979.56, p = .011). Cox proportional hazard regression showed that operative time (hazard ratio [HR] = 1.6, 95% CI: 1.15-2.22, p = .005) and CEUS enhancement pattern on postoperative day 3 (HR = 11.947, 95% CI: 2.04-69.98, p = .006) were independent predictors for graft failure. CONCLUSION Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was associated with 1-month graft failure in SLT recipients. CEUS may serve as a noninvasive, valuable prognostic tool to predict clinical outcomes early after SLT.
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Affiliation(s)
- Mei Liao
- Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China; GuangDong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China
| | - Hongjun Zhang
- Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China; GuangDong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China
| | - Jieyang Jin
- Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China; GuangDong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China
| | - Huanyi Guo
- Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China; GuangDong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China
| | - Shuhong Yi
- Guangdong Province Engineering Laboratory for Transplantation Medicine, 600 Tianhe Road, Guangzhou, China; Organ Transplantation Research Center of Guangdong Province, Guangzhou, China; Organ Transplantation Institute, Sun Yat-Sen University, Guangzhou, China; Department of Hepatic Surgery and Liver transplantation Center, the Third Affiliated Hospital, 600 Tianhe Road, Guangzhou, China
| | - Jie Ren
- Department of Ultrasound, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, PR China; GuangDong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China.
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Yang Y, Xu L, Atkins C, Kuhlman L, Zhao J, Jeong JM, Wen Y, Moreno N, Kim KH, An YA, Wang F, Bynon S, Villani V, Gao B, Brombacher F, Harris R, Eltzschig HK, Jacobsen E, Ju C. Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury. Gut 2024; 73:1543-1553. [PMID: 38724220 PMCID: PMC11347249 DOI: 10.1136/gutjnl-2024-332033] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024]
Abstract
OBJECTIVE Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.
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Affiliation(s)
- Yang Yang
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Long Xu
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Constance Atkins
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Lily Kuhlman
- The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jie Zhao
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Jong-Min Jeong
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Yankai Wen
- The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Nicolas Moreno
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Kang Ho Kim
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Yu A An
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Fenfen Wang
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Steve Bynon
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Vincenzo Villani
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Bin Gao
- Laboratory of Liver Disease, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA
| | - Frank Brombacher
- University of Cape Town Faculty of Health Sciences, Observatory, Western Cape, South Africa
| | - Raymond Harris
- Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Holger K Eltzschig
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Elizabeth Jacobsen
- Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Cynthia Ju
- Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
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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: 0] [Impact Index Per Article: 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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Varghese RK, Handing GE, Montgomery AE, Rana AA, Goss JA. Retrospective Analysis of the Impact of High- and Low-Quality Donor Livers for Patients with High-Acuity Illness. Ann Transplant 2024; 29:e941931. [PMID: 38192097 PMCID: PMC10787593 DOI: 10.12659/aot.941931] [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: 01/10/2024] Open
Abstract
BACKGROUND Patients with high-acuity liver failure have increased access to marginal and split liver options, owing to historically high waitlist mortality rates. While most research states that donor liver quality has no impact on patients with high-acuity illness, there have been inconsistencies in recent research on how liver quality impacts post-transplant outcomes for these patients. We aimed to quantify donor liver quality with various post-transplantation patient outcomes for patients with high-acuity illness. MATERIAL AND METHODS Using the liver donor risk index (LDRI), model for end stage liver disease (MELD), and clinically relevant recipient factors, we used multivariate logistic regression to analyze how donor liver quality affects varying measures of patient outcomes for 9923 high-acuity patients from June 18, 2013, to June 18, 2022. RESULTS Using LDRI, high-quality livers had a significant protective impact on high-acuity patient mortality, compared with low-quality livers (OR=0.695 [0.549, 0.879], P=0.002). High-quality livers also had significant impact on graft survival (OR=0.706 [0.558, 0.894], P=0.004). Two sensitivity patient mortality analyses, excluding patients with status 1A and hepatocellular carcinoma, showed significant protective findings for high-quality livers. High-quality livers had insignificant outcomes on long-term survivor mortality, length of hospitalization, and primary non-function outcomes, compared with low-quality donor livers. CONCLUSIONS While our findings suggest donor quality has an impact on high-acuity patient outcomes, these findings indicate further research is needed in intent-to-treat analysis on clinical offer data to provide a clearer finding of how donor quality affects patients with high-acuity illness.
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Affiliation(s)
- Ron K Varghese
- Office of Student Affairs, Baylor University, Waco, TX, USA
| | - Greta E Handing
- Office of Student Affairs, Baylor College of Medicine, Houston, TX, USA
| | | | - Abbas A Rana
- Division of Abdominal Transplantation, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
| | - John A Goss
- Division of Abdominal Transplantation, Michael E. Debakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
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Shubin AD, MacConmara MP, Patel MS, Wang BK, Feizpour CA, Reese J, Niles PA, Shah JA, Desai DM, De Gregorio L, Hanish SI, Vagefi PA, Hwang CS. No Stone Left Unturned: Utilization of an Organ Procurement Organization Donor Surgeon at Procurement Reduces Discards of Marginal Liver Allografts. Transplantation 2023; 107:648-653. [PMID: 36253907 DOI: 10.1097/tp.0000000000004367] [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: 11/25/2022]
Abstract
BACKGROUND The recent trend of organ procurement organizations (OPOs) employing independent surgeons for organ procurement has been developed with the goal of improving the supply of suitable organs for transplantation. We investigated the effects that the addition of an OPO-employed, organ-procurement specialist has on liver allograft discard rate, marginal organ utilization, and graft survival. METHODS Organ Procurement and Transplant Network and OPO data were retrospectively studied between April 1, 2014' and July 31, 2019' within the Southwest Transplant Alliance donor service area. Liver procurements with an OPO-surgeon present (OPO-Present) were compared to those without the involvement of an OPO surgeon (OPO-Absent). Donor and recipient characteristics as well as outcomes were analyzed across groups using propensity score matching. RESULTS In total 869 OPO-Present liver allografts had similar rates of discard (5.2%) compared to 771 OPO-Absent livers (5.8%). However, after adjusting for donor risk, OPO-Present livers had a lower propensity of discard compared to OPO-Absent (3.4% versus 7.6%, P < 0.05). OPO-Present livers were more likely to be shared nationally (11.0% versus 4.8%, P < 0.001). Outcome analysis showed allograft survival of OPO-Present livers at 5 y was comparable to OPO-Absent livers (79.5% versus 80%, P = 0.34). CONCLUSIONS The presence of an OPO surgeon was associated with decreased liver allograft discard and increased utilization of marginal donor organs. The OPO surgeon's presence represents a potential strategy to increase organ utilization nationally.
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Affiliation(s)
- Andrew D Shubin
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | | | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Benjamin K Wang
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Cyrus A Feizpour
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | | | | | - Jigesh A Shah
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Dev M Desai
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Lucia De Gregorio
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven I Hanish
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Parsia A Vagefi
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Christine S Hwang
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
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Zhong L, Jin Y, Gu Y, He W, Zheng Y, Yang T, Li Y, Fu L, Zhang W, Xu Q. Clinically ill patients' experiences of early mobilisation after liver transplantation: a qualitative study using Pender's health promotion model. Int J Rehabil Res 2023; 46:92-97. [PMID: 36727671 PMCID: PMC9907680 DOI: 10.1097/mrr.0000000000000566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 01/04/2023] [Indexed: 02/03/2023]
Abstract
The aim of this study is to explore the factors influencing early mobilisation behaviours and patients' needs in critically ill patients after liver transplantation (LT). This interview study used phenomenological research, and Pender's health promotion model (HPM) was used to construct the interview guide. With the use of purposeful sampling, a total of 19 critically ill patients who experienced early mobilisation after LT were recruited at three tertiary hospitals in Beijing from August to November 2022. Data were collected through semi-structured interviews and analysed using Colaizzi's seven-step method. Nine themes were categorised into the three domains of Pender's HPM. The first domain was individual characteristics and experiences: (1) symptoms of end-stage liver disease limiting premobility behaviours and (2) previous treatment experience affecting understanding of early mobilisation after LT. The second domain was behaviour-specific cognition and affect: (3) coexistence of benefits and concerns in early mobilisation after LT, (4) barriers to early mobilisation after LT, (5) high self-efficacy in early mobilisation after LT, (6) individual differences in early mobilisation and (7) support and encouragement from family, wardmates and medical staff. The final domain was behavioural outcomes: (8) the need for sufficient staff, a quiet environment, safety, goals, guidance and family participation and (9) a strong willingness to comply with early mobilisation plans. The three areas and nine themes extracted in this study are helpful for the long-term development of early mobilisation in patients after LT.
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Affiliation(s)
| | - Yanhong Jin
- Department of Nursing, Beijing Friendship Hospital
| | - Yanmei Gu
- Department of Intensive Care Medicine, Beijing Youan Hospital, Capital Medical University
| | | | - Yulin Zheng
- Department of Intensive Care Medicine, Beijing Youan Hospital, Capital Medical University
| | - Tongnan Yang
- Department of Liver Intensive Care Unit, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | | | - Li Fu
- Department of Intensive Care Medicine
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9
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Braga VS, Boteon APCS, Paglione HB, Pecora RAA, Boteon YL. Extended criteria brain-dead organ donors: Prevalence and impact on the utilisation of livers for transplantation in Brazil. World J Hepatol 2023; 15:255-264. [PMID: 36926240 PMCID: PMC10011911 DOI: 10.4254/wjh.v15.i2.255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/17/2023] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Despite its association with higher postoperative morbidity and mortality, the use of extended criteria donor (ECD) livers for transplantation has increased globally due to the high demand for the procedure. AIM To investigate the prevalence of ECD in donation after brain death (DBD) and its impact on organ acceptance for transplantation. METHODS Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre. The incidence of the Eurotransplant risk factors to define an ECD (ET-ECD) among DBD donors and the likelihood of organ acceptance over the years were analysed. The relationship between organ refusal for transplantation, the occurrence, and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment. RESULTS A total of 1619 organ donors were evaluated. Of these, 78.31% (n = 1268) had at least one ET-ECD criterion. There was an increase in the acceptance of ECD DBD organs for transplantation (1 criterion: from 23.40% to 31.60%; 2 criteria: from 13.10% to 27.70%; 3 criteria: From 6.30% to 13.60%). For each addition of one ET-ECD variable, the estimated chance of organ refusal was 64.4% higher (OR 1.644, 95%CI 1.469-1.839, P < 0.001). Except for the donor serum sodium > 165 mmol/L (P = 0.310), all ET-ECD criteria increased the estimated chance of organ refusal for transplantation. CONCLUSION A high prevalence of ECD DBD was observed. Despite the increase in their utilisation, the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.
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Affiliation(s)
- Victoria S Braga
- Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Amanda P C S Boteon
- Transplant Centre, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Heloisa B Paglione
- Transplant Centre, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Rafael A A Pecora
- Transplant Centre, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
| | - Yuri L Boteon
- Transplant Centre, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil.
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10
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Radiomic analysis of liver grafts from brain-dead donors can predict early allograft dysfunction following transplantation: a proof-of-concept study. HPB (Oxford) 2022; 24:1527-1534. [PMID: 35382981 DOI: 10.1016/j.hpb.2022.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 03/04/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Selection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon's subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD). METHODS We retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD. RESULTS From 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72-0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor's CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84-0.96). A validation cohort of 23 patients confirmed these results. CONCLUSION Radiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT.
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11
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Takemura Y, Shinoda M, Takemura R, Hasegawa Y, Yamada Y, Obara H, Kitago M, Sakamoto S, Kasahara M, Umeshita K, Eguchi S, Ohdan H, Egawa H, Kitagawa Y. Development of a risk score model for 1-year graft loss after adult deceased donor liver transplantation in Japan based on a 20-year nationwide cohort. Ann Gastroenterol Surg 2022; 6:712-725. [PMID: 36091314 PMCID: PMC9444863 DOI: 10.1002/ags3.12573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/10/2022] [Accepted: 03/25/2022] [Indexed: 11/18/2022] Open
Abstract
Aim Using nationwide data collected over the past 20 years, we aimed to investigate deceased donor liver transplantation (DDLT) outcomes to develop a unique risk model that can be used to establish a standard for organ acceptance in Japan. Methods Data were collected for 449 recipients aged ≥18 years who underwent DDLT between 1999 and 2019. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to develop an original risk score model for 1-year graft loss (termed the Japan Risk Index [JRI]). We developed risk indices according to recipient, donor, and surgery components (termed JRI-R, D, and S, respectively). The JRI was validated via a 5-fold cross-validation. We also compared DDLT outcomes and risk indices among Era1 (-2011), Era2 (-2015), and Era3 (-2019). Results The 1-year graft survival rate was 89.5% and improved significantly, reaching 84.7%, 87.6%, and 93.9% in Era1, Era2, and Era3, respectively. The JRI was calculated as JRI-R (re-transplantation, Model for End-Stage Liver Disease score, medical condition in intensive care unit) × JRI-D (age, catecholamine index, maximum sodium, maximum total bilirubin) × JRI-S (total ischemic time) × 0.84. The risk model achieved a mean C-statistic value of 0.81 in the validation analysis. The risk index was significantly lower in Era3 than in Era2. Conclusion Changes in the risk index over time indicated that avoiding risks contributed to the improved outcomes in Era3. The JRI is unique to adult DDLT in Japan and may be useful as a reference for organ acceptance in the future.
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Affiliation(s)
- Yusuke Takemura
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Masahiro Shinoda
- Digestive Disease CenterMita HospitalInternational University of Health and WelfareTokyoJapan
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research CenterKeio University School of MedicineTokyoJapan
| | - Yasushi Hasegawa
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Yohei Yamada
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Hideaki Obara
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Minoru Kitago
- Department of SurgeryKeio University School of MedicineTokyoJapan
| | - Seisuke Sakamoto
- Organ Transplantation CenterNational Center for Child Health and DevelopmentTokyoJapan
| | - Mureo Kasahara
- Organ Transplantation CenterNational Center for Child Health and DevelopmentTokyoJapan
| | - Koji Umeshita
- Division of Health ScienceOsaka University Graduate School of MedicineOsakaJapan
| | - Susumu Eguchi
- Department of SurgeryNagasaki University Graduate School of Biomedical ScienceNagasakiJapan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant SurgeryHiroshima University Graduate School of Biomedical and Health SciencesHiroshimaJapan
| | - Hiroto Egawa
- Department of SurgeryInstitute of GastroenterologyTokyo Women's Medical UniversityTokyoJapan
| | - Yuko Kitagawa
- Department of SurgeryKeio University School of MedicineTokyoJapan
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12
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Manzia TM, Lai Q, Hartog H, Aijtink V, Pellicciaro M, Angelico R, Gazia C, Polak WG, Rossi M, Tisone G. Graft weight integration in the early allograft dysfunction formula improves the prediction of early graft loss after liver transplantation. Updates Surg 2022; 74:1307-1316. [PMID: 35306614 PMCID: PMC9338117 DOI: 10.1007/s13304-022-01270-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 03/02/2022] [Indexed: 11/13/2022]
Abstract
The role of the graft-to-recipient weight ratio (GRWR) in adult liver transplantation (LT) has been poorly investigated so far. The aim is to evaluate the contribution of the GRWR to the well-recognized early allograft dysfunction (EAD) model (i.e., Olthoff model) for the prediction of 90-day graft loss after LT in adults. Three hundred thirty-one consecutive adult patients undergoing LT between 2009 and 2018 at Tor Vergata and Sapienza University in Rome, Italy, served as the Training-Set. The Validation-Set included 123 LTs performed at the Erasmus Medical Center, Rotterdam, the Netherlands. The mEAD model for 90-day graft loss included the following variables: GRWR [Formula: see text] 1.57 = 2.5, GRWR [Formula: see text] 2.13 = 2.5, total bilirubin ≥ 10.0 mg/dL = 2.0, INR ≥ 1.60 = 2.3, and aminotransferase > 2000 IU/L = 2.2. The mEAD model showed an AUC = 0.74 (95%CI = 0.66-0.82; p < 0.001) and AUC = 0.68 (95%CI = 0.58-0.88; p = 0.01) in the Training-Set and Validation-Set, respectively, outperforming conventional EAD in both cohorts (Training-Set: AUC = 0.64, 95%CI = 0.57-0.72; p = 0.001; Validation-Set: AUC = 0.52, 95%CI = 0.35-0.69, p = 0.87). Incorporation of graft weight in a composite multivariate model allowed for better prediction of patients who presented an aminotransferase peak > 2000 IU/L after LT (OR = 2.39, 95%CI = 1.47-3.93, p = 0.0005). The GRWR is important in determining early graft loss after adult LT, and the mEAD model is a useful predictive tool in this perspective, which may assist in improving the graft allocation process.
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Affiliation(s)
- Tommaso Maria Manzia
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Quirino Lai
- Department of Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
- General Surgery and Organ Transplantation Unit, Department of General and Specialistic Surgery, Umberto I Polyclinic of Rome, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
| | - Hermien Hartog
- Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Virginia Aijtink
- Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Marco Pellicciaro
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Roberta Angelico
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Carlo Gazia
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
| | - Wojciech G Polak
- Division of Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Massimo Rossi
- Department of Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Giuseppe Tisone
- Department of Surgery Science, University of Rome Tor Vergata, U.O.C. Chirurgia Epatobiliare e Trapianti, Fondazione PTV, Rome, Italy
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13
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Incidence of Ischemia Reperfusion Injury Related Biliary Complications in Liver Transplantation: Effect of Different Types of Donors. Transplant Proc 2022; 54:1865-1873. [DOI: 10.1016/j.transproceed.2022.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 04/07/2022] [Accepted: 05/02/2022] [Indexed: 11/19/2022]
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14
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Vilatobá M, González-Duarte A, Cruz-Martínez R, García-Juárez I, Leal-Villalpando R. First two cases of domino liver transplantation in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2022; 87:386-388. [DOI: 10.1016/j.rgmxen.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 10/06/2021] [Indexed: 10/18/2022]
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15
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Ghinolfi D, Lai Q, Carrai P, Petruccelli S, Morelli M, Melandro F, Biancofiore G, De Simone P. The impact of hepatitis C virus direct acting agents in liver transplant using very old donor grafts: a real-world single-center analysis. Updates Surg 2022; 74:557-570. [PMID: 34807412 DOI: 10.1007/s13304-021-01204-2] [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: 09/09/2021] [Accepted: 11/12/2021] [Indexed: 10/19/2022]
Abstract
The correct timing of use of direct acting agents (DAAs) among transplanted patients remains unknown. The aim of this paperwork is to evaluate the impact of DAAs treatment in pre- or peri-operative period in liver transplantation when grafts ≥ 70 years are used. This is a retrospective analysis comparing adult liver transplant performed for HCV-related cirrhosis and/or hepatocarcinoma using a graft ≥ 70 in the period 2015-2018 (Group DAA-HCV-OLD, study group) to three different groups: (a) anti-HCV-Ab-negative patients receiving graft ≥ 70 (no-HCV-OLD), (b) anti-HCV-Ab-negative patients receiving a graft aged 18-69 years (no-HCV-YOUNG), and (c) anti-HCV-Ab-positive patients receiving a donor graft ≥ 70 in the period 2007-2011 (no-DAA-HCV-OLD). Totally, 528 liver transplants were considered: 164 in DAA-HCV-OLD, 143 in no-HCV-OLD, 120 in no-HCV-YOUNG and 101 in no-DAA-HCV-OLD Group. Graft survival rates at 1 and 3 years were 88% and 81% in DAA-HCV-OLD Group, 82% and 68% in no-DAA-HCV-OLD (p = 0.007), 89% and 84% in no-HCV-OLD (p = 0.76), and 94% and 92% in no-HCV-YOUNG (p = 0.02). No differences were observed among groups in the incidence of primary non-function, primary dysfunction, vascular or biliary complications. DAAs were able to zero HCV-related graft loss, with a 3-year graft survival > 80%. The outcomes of older graft recipients became equal irrespectively of their HCV serological status.
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Affiliation(s)
- Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Tuscany, Italy.
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Paola Carrai
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Tuscany, Italy
| | - Stefania Petruccelli
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Tuscany, Italy
| | - Marta Morelli
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Tuscany, Italy
| | | | | | - Paolo De Simone
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124, Pisa, Tuscany, Italy
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16
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An Assessment of Ineligible Donor Use in Solid Organ Transplant. Transplantation 2022; 106:1629-1637. [DOI: 10.1097/tp.0000000000004084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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17
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Chen S, Wang T, Luo T, He S, Huang C, Jia Z, Zhan L, Wang D, Zhu X, Guo Z, He X. Prediction of Graft Survival Post-liver Transplantation by L-GrAFT Risk Score Model, EASE Score, MEAF Scoring, and EAD. Front Surg 2021; 8:753056. [PMID: 34869560 PMCID: PMC8641658 DOI: 10.3389/fsurg.2021.753056] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/12/2021] [Indexed: 01/14/2023] Open
Abstract
Background: Early allograft dysfunction (EAD) is correlated with poor patient or graft survival in liver transplantation. However, the power of distinct definitions of EAD in prediction of graft survival is unclear. Methods: This retrospective, single-center study reviewed data of 677 recipients undergoing orthotopic liver transplant between July 2015 and June 2020. The following EAD definitions were compared: liver graft assessment following transplantation (L-GrAFT) risk score model, early allograft failure simplified estimation score (EASE), model for early allograft function (MEAF) scoring, and Olthoff criteria. Risk factors for L-GrAFT7 high risk group were evaluated with univariate and multivariable logistic regression analysis. Results: L-GrAFT7 had a satisfied C-statistic of 0.87 in predicting a 3-month graft survival which significantly outperformed MEAF (C-statistic = 0.78, P = 0.01) and EAD (C-statistic = 0.75, P < 0.001), respectively. L-GrAFT10, EASE was similar to L-GrAFT7, and they had no statistical significance in predicting survival. Laboratory model for end-stage liver disease score and cold ischemia time are risk factors of L-GrAFT7 high-risk group. Conclusion: L-GrAFT7 risk score is capable for better predicting the 3-month graft survival than the MEAF and EAD in a Chinese cohort, which might standardize assessment of early graft function and serve as a surrogate endpoint in clinical trial.
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Affiliation(s)
- Shirui Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Tielong Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Tao Luo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Shujiao He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Changjun Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Zehua Jia
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Liqiang Zhan
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Dongping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China
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18
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Gómez-Gavara C, Moya-Herraiz Á, Hervás D, Pérez-Rojas J, LaHoz A, López-Andújar R. The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial. Transplantation 2021; 105:2245-2254. [PMID: 33044432 DOI: 10.1097/tp.0000000000003487] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. OBJECTIVE To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. METHODS Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). RESULTS The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). CONCLUSIONS N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.
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Affiliation(s)
- Concepción Gómez-Gavara
- Department of HPB Surgery and Transplants, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Ángel Moya-Herraiz
- Department of HPB Surgery, Castellon General Hospital, CEU Cardenal Herrera University, Alfara del Patriarca, Spain
| | - David Hervás
- Statistics Unit, La Fe University Hospital, Valencia, Spain
| | - Judith Pérez-Rojas
- Pathological Anatomy Department, La Fe University Hospital, Valencia, Spain
| | - Agustín LaHoz
- Biomarkers and Precision Medicine Unit, IIS La Fe, Valencia, Spain
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19
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Masior Ł, Grąt M. Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma. Int J Mol Sci 2021; 22:8229. [PMID: 34360995 PMCID: PMC8347959 DOI: 10.3390/ijms22158229] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 07/18/2021] [Accepted: 07/29/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: "ischemia reperfusion injury", "liver transplantation", "hepatocellular carcinoma", "preconditioning", "machine perfusion".
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Affiliation(s)
- Łukasz Masior
- Department of General, Vascular and Oncological Surgery, Medical University of Warsaw, Stępińska Street 19/25, 00-739 Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, 02-097 Warsaw, Poland;
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20
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Al-Kurd A, Kitajima T, Delvecchio K, Tayseer Shamaa M, Ivanics T, Yeddula S, Yoshida A, Rizzari M, Collins K, Abouljoud M, Nagai S. Short recipient warm ischemia time improves outcomes in deceased donor liver transplantation. Transpl Int 2021; 34:1422-1432. [PMID: 34170584 DOI: 10.1111/tri.13962] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/10/2021] [Accepted: 05/13/2021] [Indexed: 12/28/2022]
Abstract
While adverse effects of prolonged recipient warm ischemia time (rWIT) in liver transplantation (LT) have been well investigated, few studies have focused on possible positive prognostic effects of short rWIT. We aim to investigate if shortening rWIT can further improve outcomes in donation after brain death liver transplant (DBD-LT). Primary DBD-LT between 2000 and 2019 were retrospectively reviewed. Patients were divided according to rWIT (≤30, 31-40, 41-50, and >50 min). The requirement of intraoperative transfusion, early allograft dysfunction (EAD), and graft survival were compared between the rWIT groups. A total of 1,256 patients of DBD-LTs were eligible. rWIT was ≤30min in 203 patients (15.7%), 31-40min in 465 patients (37.3%), 41-50min in 353 patients (28.1%), and >50min in 240 patients (19.1%). There were significant increasing trends of transfusion requirement (P < 0.001) and increased estimated blood loss (EBL, P < 0.001), and higher lactate level (P < 0.001) with prolongation of rWIT. Multivariable logistic regression demonstrated the lowest risk of EAD in the WIT ≤30min group. After risk adjustment, patients with rWIT ≤30 min showed a significantly lower risk of graft loss at 1 and 5-years, compared to other groups. The positive prognostic impact of rWIT ≤30min was more prominent when cold ischemia time exceeded 6 h. In conclusion, shorter rWIT in DBD-LT provided significantly better post-transplant outcomes.
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Affiliation(s)
- Abbas Al-Kurd
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Toshihiro Kitajima
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Khortnal Delvecchio
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Mhd Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Sirisha Yeddula
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Michael Rizzari
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Kelly Collins
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Henry Ford Transplant Institute, Detroit, MI, USA
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21
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Ju C, Wang M, Tak E, Kim B, Emontzpohl C, Yang Y, Yuan X, Kutay H, Liang Y, Hall DR, Dar WA, Bynon JS, Carmeliet P, Ghoshal K, Eltzschig HK. Hypoxia-inducible factor-1α-dependent induction of miR122 enhances hepatic ischemia tolerance. J Clin Invest 2021; 131:140300. [PMID: 33792566 PMCID: PMC8011886 DOI: 10.1172/jci140300] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 02/10/2021] [Indexed: 12/29/2022] Open
Abstract
Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction of miR122 and identified the oxygen-sensing prolyl hydroxylase domain 1 (PHD1) as a miR122 target. Further studies indicated that HIF1α-dependent induction of miR122 participated in a feed-forward pathway for liver protection via the enhancement of hepatic HIF responses through PHD1 repression. Moreover, pharmacologic studies utilizing nanoparticle-mediated miR122 overexpression demonstrated attenuated liver injury. Finally, proof-of-principle studies in patients undergoing orthotopic liver transplantation showed elevated miR122 levels in conjunction with the repression of PHD1 in post-ischemic liver biopsies. Taken together, the present findings provide molecular insight into the functional role of miR122 in enhancing hepatic ischemia tolerance and suggest the potential utility of pharmacologic interventions targeting miR122 to dampen hepatic injury during liver transplantation.
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Affiliation(s)
- Cynthia Ju
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Meng Wang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Eunyoung Tak
- Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Boyun Kim
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Christoph Emontzpohl
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Yang Yang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Xiaoyi Yuan
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - Huban Kutay
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
| | - Yafen Liang
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
| | - David R. Hall
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Wasim A. Dar
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - J. Steve Bynon
- Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Peter Carmeliet
- Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, and
- Center for Cancer Biology, Department of Oncology, Katholieke University Leuven, Leuven, Belgium
| | - Kalpana Ghoshal
- Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
- Department of Pathology, The Ohio State University, Columbus, Ohio, USA
| | - Holger K. Eltzschig
- Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA
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22
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Zhang XM, Fan H, Wu Q, Zhang XX, Lang R, He Q. In-hospital mortality of liver transplantation and risk factors: a single-center experience. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:369. [PMID: 33842590 PMCID: PMC8033294 DOI: 10.21037/atm-20-5618] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Background Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and acute liver failure. However, in-hospital death cannot be avoided. We designed this study to analyze patients' in-hospital mortality rate after LT and the factors correlated with in-hospital death. Methods The data of patients who received LT in our hospital between January 11, 2015, and November 19, 2019, were obtained from the China Liver Transplant Registry and medical records. The in-hospital mortality rate was calculated, and factors related to mortality, cause of death, and factors related to cause of death were analyzed by reviewing patients' data. Results A total of 529 patients who underwent cadaveric LT were enrolled in this study. Modified piggyback orthotopic LT was performed for all patients. Seventy patients died in the hospital after LT, and the in-hospital mortality rate was 13.2%. Factors including model for end-stage liver disease (MELD) score, Child-Pugh grading, intraoperative blood loss, and anhepatic phase were correlated with in-hospital death. MELD score and intraoperative blood loss were determined as the two independent risk factors of in-hospital death. The first two causes of death were infection (34.3%) and primary non-function (15.7%). Pulmonary fungal infection was the main cause of infectious death. MELD score was the independent risk factor for infectious death, and both body mass index of donors and cold ischemic time were independent risk factors of primary non-function. Conclusions In-hospital death poses a threat to certain patients undergoing LT. Our study suggests that the main cause of in-hospital death is an infection, followed by primary non-function.
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Affiliation(s)
- Xing-Mao Zhang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hua Fan
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiao Wu
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xin-Xue Zhang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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23
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Eichelmann AK, Vogel T, Fuchs AK, Houben P, Katou S, Becker F, Schmidt HH, Wilms C, Pascher A, Brockmann JG. Short- and Long-Term Outcomes of Different Reperfusion Sequences in Liver Transplantation. Ann Transplant 2021; 26:e926847. [PMID: 33602890 PMCID: PMC7901155 DOI: 10.12659/aot.926847] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Although most centers perform primary portal vein reperfusion (PV) in orthotopic liver transplantation (OLT) for historical reasons, there is so far no sound evidence as to whether this technique is superior. The present study evaluated the long-term outcome of 3 different reperfusion sequences: PV vs primary arterial (A) vs simultaneous reperfusion (SIM). Material/Methods All patients at our center who underwent OLT (who received a primary, whole-organ liver graft) from 2006 to 2007 were evaluated for analysis. Results A total of 61 patients were found eligible (PV: 25, A: 22, SIM: 14). Twenty-one patients (35%) were still alive after the follow-up period of 12 years. Despite poorer starting conditions such as higher recipient age (59 y (SIM) vs 55 y (A) vs 50 y (PV), P=0.01) and donor age (56 y (SIM) vs 51 y (PV) vs 50 y (A), n.s.), higher MELD scores (22 vs 19 (PV) vs 17 (A), n.s.), as well as a higher number of marginal donor organs (79% (SIM) vs 36% (A/PV), P=0.02), SIM-recipients demonstrated superior outcomes. Overall survival was 8.1 y (SIM), 4.8 y (PV), and 5.9 y (A, n.s.)). None of the SIM-recipients underwent re-transplantation, while the rate was 32% in the PV-group. The 8.1 y graft survival in SIM-recipients was significantly longer than in the other 2 groups, which were 3.3 y (PV) and 5.5 y (A, P=0.013). Conclusions Although SIM-reperfused recipients were the oldest and received grafts of inferior quality, these recipients showed superior results in terms of overall patient and graft survival. Multicentric randomized controlled trials with larger study populations are required to confirm this finding.
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Affiliation(s)
- Ann-Kathrin Eichelmann
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Thomas Vogel
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Ann-Kathrin Fuchs
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Philipp Houben
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Shadi Katou
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Felix Becker
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Hartmut H Schmidt
- Department of Gastroenterology/Hepatology, University Hospital of Münster, Münster, Germany
| | - Christian Wilms
- Department of Gastroenterology/Hepatology, University Hospital of Münster, Münster, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
| | - Jens G Brockmann
- Department of General, Visceral and Transplant Surgery, University Hospital of Münster, Münster, Germany
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24
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Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion. Transplantation 2021; 106:37-47. [PMID: 33577253 DOI: 10.1097/tp.0000000000003688] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Towards the goal of utilizing more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury. METHODS Using a porcine model of donation after circulatory death (DCD), we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 minutes of warm ischemia time (WIT) followed by the administration of CD47mAb treatment or IgG control antibodies and 6 hours of normothermic extracorporeal liver perfusion (NELP). RESULTS After 6 hours of NELP, CD47mAb-treated livers with 30 or 60 minutes WIT had significantly lower ALT levels and higher bile production compared to their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower TSP-1 protein levels, lower expression of Caspase-3, and higher expression of pERK. CONCLUSIONS These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/TSP-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion, and could increase liver regeneration during normothermic perfusion of the liver.Supplemental Visual Abstract; http://links.lww.com/TP/C146.
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25
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Kong L, Lv T, Yang J, Jiang L, Yang J. Adult split liver transplantation: A PRISMA-compliant Chinese single-center retrospective case-control study. Medicine (Baltimore) 2020; 99:e23750. [PMID: 33371134 PMCID: PMC7748205 DOI: 10.1097/md.0000000000023750] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 11/17/2020] [Indexed: 02/05/2023] Open
Abstract
Although pediatric split liver transplantation (SLT) has been proven safe and the waitlist mortality rate has been successfully reduced, the safety of adult SLT has not been confirmed.Using 1:2 matching, 47 recipients who underwent adult SLT were matched to 94 of 743 recipients who underwent adult whole graft liver transplantation (WGLT). Eventually, 141 recipients were included in the case-control study. Subgroup analysis of 43 recipients in the SLT group was performed based on the presence of the middle hepatic vein (MHV) in the grafts.No significant differences in 5-year survival (80.8% vs 81.6%, P = .465) were observed between the adult SLT and WGLT groups. However, compared to recipients in the WGLT group, those in the SLT group had more Clavien-Dindo grade III-V complications, longer hospitalization duration, and higher mortality within 45 days. Furthermore, on multivariate analysis, 45-day postoperative mortality in recipients in the SLT group was mainly affected by hyperbilirubinemia within postoperative day (POD) 7-14, surgery time, and intraoperative blood loss. Subgroup analysis showed no significant differences in hyperbilirubinemia within POD 7-14, complications, and survival rate between SLTMHV(+) and SLTMHV [-].Adult SLT is safe and effective based on long-term survival rates; however, a reduction in the incidence of short-term complications is required. Non-obstructive hyperbilirubinemia within POD 7 to 14 is an independent predictor of short-term mortality after SLT.
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26
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Kitano Y, Allard MA, Nakada S, Beghdadi N, Karam V, Vibert E, Sa Cunha A, Castaing D, Cherqui D, Baba H, Adam R. Early- and long-term outcomes of liver transplantation with rescue allocation grafts. Clin Transplant 2020; 35:e14046. [PMID: 32686220 DOI: 10.1111/ctr.14046] [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: 02/24/2020] [Revised: 06/20/2020] [Accepted: 07/11/2020] [Indexed: 11/30/2022]
Abstract
In France, liver grafts which have been refused by at least five centers are proposed as rescue allocation (RA). The aim of this study is to clarify the feasibility and safety of RA grafts in liver transplantation (LT). Short- and long-term outcomes of patients who received RA grafts (RA group) were compared with those of patients who received standard allocation (SA) grafts (SA group). From a total of 1635 patients, 102 patients received RA grafts. Before matching, the RA group was characterized primarily by less severe liver disease, but the quality of graft was worse. After matching recipients' characteristics of 102 patients who used RA grafts with 306 patients who used SA grafts, recipients' characteristics were well balanced (1:3 matching). Although the rate of primary dysfunction was significantly higher in the RA group, there is no significant difference in the occurrence of major complications, length of hospitalization, and mortality between two groups. Graft survival (GS) and overall survival (OS) in the RA group were not significantly different from the SA group (GS; HR = 1.03 P = .89, OS; HR = 1.03 P = .90). In the French allocation system, the feasibility and safety of RA grafts might be comparable to SA grafts for carefully selected patients.
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Affiliation(s)
- Yuki Kitano
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France.,Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Marc-Antoine Allard
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Shinichiro Nakada
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France.,Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Nassiba Beghdadi
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Vincent Karam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Eric Vibert
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Antonio Sa Cunha
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Denis Castaing
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Daniel Cherqui
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - René Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Université Paris Sud, Villejuif, France
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27
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Pandya K, Sastry V, Panlilio MT, Yip TCF, Salimi S, West C, Virtue S, Wells M, Crawford M, Pulitano C, Strasser SI, McCaughan GW, Majumdar A, Liu K. Differential Impact of Extended Criteria Donors After Brain Death or Circulatory Death in Adult Liver Transplantation. Liver Transpl 2020; 26:1603-1617. [PMID: 32750732 DOI: 10.1002/lt.25859] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/30/2020] [Accepted: 07/18/2020] [Indexed: 01/01/2023]
Abstract
Using grafts from extended criteria donors (ECDs) and donation after circulatory death (DCD) donors is a strategy to address organ shortage in liver transplantation (LT). We studied the characteristics and outcomes of ECD and DCD grafts. We retrospectively studied consecutive adults who underwent deceased donor LT between 2006 and 2019. ECD was defined using modified Eurotransplant criteria. Our primary outcomes were graft and patient survival. A total of 798 grafts were used for LT, of which 93.1% were donation after brain death (DBD; 59.9% were also ECD) and 6.9% were DCD grafts (49.1% were also ECD). Among DBD graft recipients, donors having >33% liver steatosis or 3 ECD criteria resulted in poorer graft survival. Otherwise ECD graft recipients had similar graft and patient survival compared with non-ECD graft recipients. DCD graft recipients also had similar patient survival compared with DBD recipients. However, DCD grafts from an ECD appeared to have worse outcomes. DCD graft recipients experienced higher rates of early allograft dysfunction (50.9% versus 24.7%; P < 0.001) and ischemic biliopathy (16.4% versus 1.5%; P < 0.001) compared with DBD graft recipients. Use of DBD grafts from ECDs did not impact outcomes unless there was significant donor steatosis or 3 Eurotransplant criteria were met. DCD graft recipients have similar patient survival compared with DBD graft recipients as long as the donor was not an ECD. We recommend that DBD donors with 3 or more ECD features or >33% steatosis and DCD donors with any ECD features be used with caution in adult LT.
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Affiliation(s)
- Keval Pandya
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Vinay Sastry
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Mara T Panlilio
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - 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
| | - Shirin Salimi
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Claire West
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Susan Virtue
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Mark Wells
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Michael Crawford
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
| | - Carlo Pulitano
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
| | - Simone I Strasser
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
| | - Geoffrey W McCaughan
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
- Liver Injury and Cancer Program, The Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Avik Majumdar
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
| | - Ken Liu
- Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia
- Liver Injury and Cancer Program, The Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
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28
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Qu X, Zheng C, Wang B, Wang F, Sun X, Gao Y, Xia Q, Kong X. Comprehensive analysis of circular RNAs from steatotic livers after ischemia and reperfusion injury by next-generation RNA sequencing. FEBS Lett 2020; 595:99-109. [PMID: 33070312 DOI: 10.1002/1873-3468.13960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/15/2022]
Abstract
Global organ shortage has led to the acceptance of steatotic livers for transplantation, taking the risk of graft dysfunction associated with the higher sensitivity of steatotic livers to ischemia and reperfusion injury (IRI). Data about circular RNAs (circRNAs) in steatotic livers following IRI are practically nonexistent. In our study, a high-fat diet-fed mouse model of hepatic steatosis was generated, and RNA sequencing was performed both on IRI and on sham liver tissues of these mice to screen for circRNAs with significant differential expression. To further validate our bioinformatics data, one upregulated circRNA and four downregulated circRNAs were examined. The circularity of these circRNAs was demonstrated using RNaseR digestion and Sanger sequencing. The expression of four stable circRNAs undigested by RNaseR was further validated by quantitative PCR. In summary, this study unearths several circRNAs as novel and potentially effective targets involved in the more severe damage of steatotic livers following IRI.
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Affiliation(s)
- Xiaoye Qu
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.,Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Chao Zheng
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Bingrui Wang
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.,Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Fang Wang
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Xuehua Sun
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Yueqiu Gao
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Xiaoni Kong
- Institute of Clinical Immunology, Department of Liver Diseases, Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
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29
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Kong L, Lv T, Jiang L, Yang J, Yang J. A simple four-factor preoperative recipient scoring model for prediction of 90-day mortality after adult liver Transplantation:A retrospective cohort study. Int J Surg 2020; 81:26-31. [DOI: 10.1016/j.ijsu.2020.07.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/06/2020] [Accepted: 07/08/2020] [Indexed: 01/06/2023]
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30
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Dickson KM, Martins PN. Implications of liver donor age on ischemia reperfusion injury and clinical outcomes. Transplant Rev (Orlando) 2020; 34:100549. [PMID: 32498978 DOI: 10.1016/j.trre.2020.100549] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 04/14/2020] [Accepted: 04/17/2020] [Indexed: 12/11/2022]
Abstract
The aging process causes detrimental changes in a variety of organ systems. These changes include: lesser ability to cope with stress, impaired repair mechanisms and decreased cellular functional reserve capacity. Not surprisingly, aging has been associated with increased susceptibility of donor heart and kidneys grafts to ischemia reperfusion injury (IRI). In the context of liver transplantation, however, the effect of donor age seems to be less influential in predisposing the graft to IRI. In fact, a widely comprehensive understanding of IRI in the aged liver has yet to be agreed upon in the literature. Nevertheless, there have been many reported implications of increased liver donor age with poor clinical outcomes besides IRI. These other poor outcomes include: earlier HCV recurrence, increased rates of acute rejection and greater resistance to tolerance induction. While these other correlations have been identified, it is important to re-emphasize the fact that a unified consensus in regard to liver donor age and IRI has not yet been reached among researchers in this field. Many researchers have even demonstrated that the extent of IRI in aged livers can be ameliorated by careful donor selection, strict allocation or novel therapeutic modalities to decrease IRI. Thus, the goals of this review paper are twofold: 1) To delineate and summarize the conflicting data in regard to liver donor age and IRI. 2) Suggest that careful donor selection, appropriate allocation and strategic effort to minimize IRI can reduce the frequency of a variety of poor outcomes with aged liver donations.
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Affiliation(s)
- Kevin M Dickson
- Department of Surgery, Division of Transplantation, University of Massachusetts Medical School, 55 N Lake Ave, Worcester, MA 01605, USA.
| | - Paulo N Martins
- Department of Surgery, Division of Transplantation, University of Massachusetts Medical School, 55 N Lake Ave, Worcester, MA 01605, USA.
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31
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Castillo Tuñón JM, Marín Gómez LM, Suárez Artacho G, Cepeda Franco C, Bernal Bellido C, Álamo Martínez JM, Padillo Ruiz FJ, Gómez Bravo MÁ. Risk Factors for No Valid Liver Graft. Multivariate Study Based on the Variables Included in the Donation Protocol of the National Trasplant Organisation. Cir Esp 2020; 98:591-597. [PMID: 32507309 DOI: 10.1016/j.ciresp.2020.03.021] [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: 09/28/2019] [Revised: 03/21/2020] [Accepted: 03/30/2020] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Among the strategies designed to optimize the number of existing liver grafts for transplantation, the implementation of the graft assessment process is one of the least explored. The main objective is to identify the risk factors presented by liver donors for «NO validity». Secondly, we analyzed the coincidence between the surgeon's assessment and that of the anatomo-pathologist in the invalid donors. MATERIAL AND METHOD Retrospective study conducted from a prospective database that analyzes 190 liver donors, 95 valid and 95 NOT valid. The variables of each of them corresponding to the donation protocol of the National Transplant Organization are studied. Through a multivariate study we determine the independent risk factors of NO validity. We checked the causes of NO validity argued with the histopathological findings of these grafts. RESULTS The independent risk factors of non-validity in the multivariate study (P < .05) were: dyslipidemia, personal medical history other than cardiovascular and abdominal surgical risk factors, GGT, BrT, and the result of previous liver ultrasound. The 3 most frequent causes of NO validity were: steatosis, fibrosis and macroscopic appearance of the organ. 78% of the biopsies confirmed the NO validity of the graft (in 57.9% of the cases the histological findings coincided with those described by the surgeon). The 22.1% of the biopsies hadńt pathological findings. CONCLUSIONS The determination of the risk factors of NO validity will contribute to the design of future assessment scores that are useful tools in the process of liver graft assessment.).
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Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation. Transplantation 2020; 104:72-78. [DOI: 10.1097/tp.0000000000002838] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction. Hepatobiliary Pancreat Dis Int 2019; 18:423-429. [PMID: 30853253 DOI: 10.1016/j.hbpd.2019.02.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 02/18/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early allograft dysfunction (EAD) is a severe complication after liver transplantation. The associated risk factors and complications have re-gained recent interest. This study investigated risk factors, survival and complications associated with EAD in a large liver transplant center in Latin America. METHODS Retrospective, unicenter, cohort, based on data from adult patients undergoing first deceased-donor liver transplant from January 2009 to December 2013. EAD was defined by one or more of the following: (i) bilirubin ≥10 mg/dL on postoperative day 7; (ii) international normalized ratio ≥1.6 on postoperative day 7, and (iii) alanine aminotransferase or aspartate aminotransferase >2000 IU/L within the first seven days after transplant. RESULTS A total of 602 patients were included; of these 34.2% developed EAD. Donor risk factors were male (P = 0.007), age between 50 and 59 years (P = 0.034), overweight (P = 0.028) or grade I obesity (P = 0.012), sodium >157 mmol/L (P = 0.002) and grade IV ischemia/reperfusion injury (P = 0.002). Cold ischemia time ≥10 h (P = 0.008) and warm ischemia time ≥40 min (P = 0.013) were the surgical factors. Male (P <0.001) was the only recipient protective factor. Compared with the non-EAD group, patients with EAD were submitted to more reoperations (24.3% vs. 13.4%, P = 0.001) and had higher graft loss rates (37.9% vs. 21.2%, P <0.001), with similar patient survival rates (P = 0.238). CONCLUSIONS EAD risk factors are related to donor, surgical procedure and recipient. Donor risk factors for EAD were male, age between 50 and 59 years, donor overweight or grade I obesity, sodium >157 mmol/L and grade IV ischemia/reperfusion injury. Cold ischemia time ≥10 h and warm ischemia time ≥40 min were the surgical risk factors. Male was the only recipient protective factor. Patients with EAD had higher reoperations and graft loss rates.
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Patrono D, Surra A, Catalano G, Rizza G, Berchialla P, Martini S, Tandoi F, Lupo F, Mirabella S, Stratta C, Salizzoni M, Romagnoli R. Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors. Sci Rep 2019; 9:9337. [PMID: 31249370 PMCID: PMC6597580 DOI: 10.1038/s41598-019-45843-3] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 06/06/2019] [Indexed: 02/08/2023] Open
Abstract
Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2–3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.
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Affiliation(s)
- Damiano Patrono
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Astrid Surra
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Giorgia Catalano
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Giorgia Rizza
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Paola Berchialla
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Silvia Martini
- Gastrohepatology Unit, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Francesco Tandoi
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Francesco Lupo
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Stefano Mirabella
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Chiara Stratta
- Anesthesia Department 2, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Mauro Salizzoni
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
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Indocyanine green fluorescence imaging to evaluate graft perfusion during liver transplantation. HPB (Oxford) 2019; 21:387-392. [PMID: 30297305 DOI: 10.1016/j.hpb.2018.09.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 08/04/2018] [Accepted: 09/02/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary graft dysfunction (PGD) is a leading cause of graft loss after liver transplantation. There is no reliable method to anticipate this complication intraoperatively. Indocyanine green (ICG) fluorescence imaging is a technique used in hepatobiliary surgery for detection of liver malignancies, but has never been reported in the setting of liver transplantation (LT) for function assessment. We hypothesized that there could be an association between the type of fluorescence and the occurrence of PGD. METHODS We retrospectively analyzed 72 patients who underwent LT at our center. An assessment of the liver graft with the ICG fluorescence technique was carried out. A classification comprising 3 types of fluorescence was created after evaluation of the recorded images. We assessed the relationship between the type of fluorescence and the occurrence of PGD. RESULTS Crosstabulation analysis of the fluorescent types and occurrence of PGD yielded a statistically significant association (p = 0.002). Univariate analysis showed that an abnormal ICG fluorescence pattern was a risk factor for the occurrence of PGD after LT. CONCLUSIONS Our findings suggest that there could be an association between ICG fluorescence imaging and graft function. This intraoperative tool could be useful to detect patients at risk of developing PGD after LT.
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Ghinolfi D, Rreka E, De Tata V, Franzini M, Pezzati D, Fierabracci V, Masini M, Cacciatoinsilla A, Bindi ML, Marselli L, Mazzotti V, Morganti R, Marchetti P, Biancofiore G, Campani D, Paolicchi A, De Simone P. Pilot, Open, Randomized, Prospective Trial for Normothermic Machine Perfusion Evaluation in Liver Transplantation From Older Donors. Liver Transpl 2019; 25:436-449. [PMID: 30362649 DOI: 10.1002/lt.25362] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 10/17/2018] [Indexed: 12/12/2022]
Abstract
Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated.
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Affiliation(s)
- Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa, Pisa, Italy
| | - Erion Rreka
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa, Pisa, Italy
| | - Vincenzo De Tata
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Maria Franzini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Daniele Pezzati
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa, Pisa, Italy
| | - Vanna Fierabracci
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Matilde Masini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Maria Lucia Bindi
- Department of Anesthesia, Medical School Hospital, University of Pisa, Pisa, Italy
| | - Lorella Marselli
- Department of Endocrinology and Metabolism in Organ Transplantation Unit, University of Pisa, Pisa, Italy
| | | | | | - Piero Marchetti
- Department of Endocrinology and Metabolism in Organ Transplantation Unit, University of Pisa, Pisa, Italy
| | | | | | - Aldo Paolicchi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa, Pisa, Italy
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Avolio AW, Gaspari R, Teofili L, Bianco G, Spinazzola G, Soave PM, Paiano G, Francesconi AG, Arcangeli A, Nicolotti N, Antonelli M. Postoperative respiratory failure in liver transplantation: Risk factors and effect on prognosis. PLoS One 2019; 14:e0211678. [PMID: 30742650 PMCID: PMC6370207 DOI: 10.1371/journal.pone.0211678] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 01/20/2019] [Indexed: 01/01/2023] Open
Abstract
Background Postoperative respiratory failure (PRF, namely mechanical ventilation >48 hours) significantly affects morbidity and mortality in liver transplantation (LTx). Previous studies analyzed only one or two categories of PRF risk factors (preoperative, intraoperative or postoperative ones). The aims of this study were to identify PRF predictors, to assess the length of stay (LoS) in ICU and the 90-day survival according to the PRF in LTx patients. Methods Two classification approaches were used: systematic classification (recipient-related preoperative factors; intraoperative factors; logistic factors; donor factors; postoperative ICU factors; postoperative surgical factors) and patient/organ classification (patient-related general factors; native-liver factors; new-liver factors; kidney factors; heart factors; brain factors; lung factors). Two hundred adult non-acute patients were included. Missing analysis was performed. The competitive role of each factor was assessed. Results PRF occurred in 36.0% of cases. Among 28 significant PRF predictors at univariate analysis, 6 were excluded because of collinearity, 22 were investigated by ROC curves and by logistic regression analysis. Recipient age (OR = 1.05; p = 0.010), female sex (OR = 2.75; p = 0.018), Model for End-Stage Liver Disease (MELD, OR = 1.09; p<0.001), restrictive lung pattern (OR = 2.49; p = 0.027), intraoperative veno-venous bypass (VVBP, OR = 3.03; p = 0.008), pre-extubation PaCO2 (OR = 1.11; p = 0.003) and Model for Early Allograft Function (MEAF, OR = 1.37; p<0.001) resulted independent PRF risk factors. As compared to patients without PRF, the PRF-group had longer LoS (10 days IQR 7–18 versus 5 days IQR 4–7, respectively; p<0.001) and lower day-90 survival (86.0% versus 97.6% respectively, p<0.001). Conclusion In conclusion, MELD, restrictive lung pattern, surgical complexity as captured by VVBP, pre-extubation PaCO2 and MEAF are the main predictors of PRF in non-acute LTx patients.
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Affiliation(s)
- Alfonso Wolfango Avolio
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Surgery -Transplantation Service, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
- * E-mail:
| | - Rita Gaspari
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Luciana Teofili
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Institute of Hematology, Rome, Italy
| | - Giuseppe Bianco
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Surgery -Transplantation Service, Rome, Italy
| | - Giorgia Spinazzola
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Paolo Maurizio Soave
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Gianfranco Paiano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Alessandra Gioia Francesconi
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Andrea Arcangeli
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
| | - Nicola Nicolotti
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Institute of Hygiene and Epidemiology, Rome, Italy
| | - Massimo Antonelli
- Università Cattolica del Sacro Cuore, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Anaesthesiology and Intensive Care Medicine, Rome, Italy
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Ghinolfi D, Gianardi D, Cirillo G, De Simone P, Pezzati D, Arenga G, Battaglia V, Filipponi F. Successful Transplant of a Nonagenarian Liver Graft With Fully Replaced Right Hepatic Artery Reconstruction. EXP CLIN TRANSPLANT 2019; 17:121-123. [DOI: 10.6002/ect.2016.0179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Kato H, Duarte S, Miller MG, Busuttil RW, Coito AJ. Overproduction of Tenascin-C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice. Liver Transpl 2019; 25:288-301. [PMID: 30358115 PMCID: PMC6355355 DOI: 10.1002/lt.25365] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 10/17/2018] [Indexed: 01/08/2023]
Abstract
The purpose of this study was to assess the significance of tenascin-C (Tnc) expression in steatotic liver ischemia/reperfusion injury (IRI). The critical shortage in donor organs has led to the use of steatotic livers in transplantation regardless of their elevated susceptibility to hepatic IRI. Tnc is an endogenous danger signal extracellular matrix molecule involved in various aspects of immunity and tissue injury. In the current study, mice were fed with a steatosis-inducing diet and developed approximately 50% hepatic steatosis, predominantly macrovesicular, before being subjected to hepatic IRI. We report here that lipid accumulation in hepatocytes inflated the production of Tnc in steatotic livers and in isolated hepatic stellate cells. Moreover, we show that the inability of Tnc-/- deficient steatotic mice to express Tnc significantly protected these mice from liver IRI. Compared with fatty controls, Tnc-/- steatotic mice showed significantly reduced serum transaminase levels and enhanced liver histological preservation at both 6 and 24 hours after hepatic IRI. The lack of Tnc expression resulted in impaired lymphocyte antigen 6 complex, locus (Ly6G) neutrophil and macrophage antigen-1 (Mac-1) leukocyte recruitment as well as in decreased expression of proinflammatory mediators (interleukin 1β, tumor necrosis factor α, and chemokine [C-X-C motif] ligand 2) after liver reperfusion. Myeloperoxidase (MPO) is the most abundant cytotoxic enzyme secreted by neutrophils and a key mediator of neutrophil-induced oxidative tissue injuries. Using an in vitro model of steatosis, we also show that Tnc markedly potentiated the effect of steatotic hepatocytes on neutrophil-derived MPO activity. In conclusion, our data support the view that inhibition of Tnc is a promising therapeutic approach to lessen inflammation in steatotic livers and to maximize their successful use in organ transplantation.
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Affiliation(s)
- Hiroyuki Kato
- The Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles CA
| | - Sergio Duarte
- The Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles CA
| | - Mary G. Miller
- The Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles CA
| | - Ronald W. Busuttil
- The Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles CA
| | - Ana J. Coito
- The Dumont‐UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles CA
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Prevalence of Steatosis Hepatis in the Eurotransplant Region: Impact on Graft Acceptance Rates. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2018; 2018:6094936. [PMID: 30515073 PMCID: PMC6236971 DOI: 10.1155/2018/6094936] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/17/2018] [Indexed: 12/11/2022]
Abstract
Due to the shortage of liver allografts and the rising prevalence of fatty liver disease in the general population, steatotic liver grafts are considered for transplantation. This condition is an important risk factor for the outcome after transplantation. We here analyze the characteristics of the donor pool offered to the Charité – Universitätsmedizin Berlin from 2010 to 2016 with respect to liver allograft nonacceptance and steatosis hepatis. Of the 2653 organs offered to our center, 19.9% (n=527) were accepted for transplantation, 58.8% (n=1561) were allocated to other centers, and 21.3% (n = 565) were eventually discarded from transplantation. In parallel to an increase of the incidence of steatosis hepatis in the donor pool from 20% in 2010 to 30% in 2016, the acceptance rates for steatotic organs increased in our center from 22.3% to 51.5% in 2016 (p < 0.001), with the majority (86.9%; p > 0.001) having less than 30% macrovesicular steatosis hepatis. However, by 2016, the number of canceled transplantations due to higher grades of steatosis hepatis had significantly increased from 14.7% (n = 15) to 63.6% (42; p < 0.001). The rising prevalence of steatosis hepatis in the donor pool has led to higher acceptance rates of steatotic allografts. Nonetheless, steatosis hepatis remains a predominant phenomenon in discarded organs necessitating future concepts such as organ reconditioning to increase graft utilization.
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Abstract
Graft dysfunction of the liver allograft manifests across a spectrum in both timing posttransplantation and clinical presentation. This can range from mild transient abnormalities of liver tests to acute liver failure potentially leading to graft failure. The causes of graft dysfunction can be divided into those resulting in early and late graft dysfunction. Although nonspecific, liver biochemistry abnormalities are still the mainstay investigation used in monitoring for dysfunction. This article provides a summary of the main causes and management strategies for liver graft dysfunction in the early through late posttransplant stages.
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Affiliation(s)
- Beverley Kok
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G-2X8, Canada
| | - Victor Dong
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G-2X8, Canada
| | - Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, Alberta T6G-2X8, Canada.
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Kim J, Martin A, Yee J, Fojut L, Geurts AM, Oshima K, Zimmerman MA, Hong JC. Effects of Hepatic Ischemia-Reperfusion Injuries and NRF2 on Transcriptional Activities of Bile Transporters in Rats. J Surg Res 2018; 235:73-82. [PMID: 30691853 DOI: 10.1016/j.jss.2018.09.057] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 09/07/2018] [Accepted: 09/19/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND The effect of hepatic ischemia-reperfusion injury (IRI) on bile transporter (BT) gene expression is unknown. We hypothesized that abnormal expression of BTs during hepatic IRI is dependent on nuclear factor erythroid 2-related factor 2 (NRF2), which contributes to the cholestasis after reperfusion. METHODS Sham surgery and short (60 min) or long (90 min) periods of warm ischemia time (WIT) with or without reperfusion for 24 h were applied to wild-type Sprague-Dawley rats and Nrf2 knockout rats (n = 5 per group). At each stage of IRI, the serum levels of aminotransferase, total bilirubin, and bile acids were measured. In addition, hepatic tissue was sampled to determine the histologic score of IRI (Suzuki score), measure adenosine triphosphate (ATP), and identify the quantitative real-time polymerase chain reactions of BTs (Oatp1, Ntcp, Mrp2, Bsep, and Mrp3). RESULTS In short periods of WIT, BT expression increased during the ischemia stage and returned to the baseline after reperfusion. However, in long periods of WIT, BT expression did not increase after ischemia and decreased further after reperfusion. Short WIT did not increase BT expression in Nrf2 knockout animals. The level of BT expression was correlated with the Suzuki score, the serum levels of aminotransferase, bilirubin, and bile acids, and tissue ATP level. Stepwise multiple regression analysis derived equations to predict the Suzuki score (R2 = 76.8, P < 0.001), serum total bilirubin (R2 = 61.2, P < 0.001), and tissue ATP (R2 = 61.1, P < 0.001). CONCLUSIONS Short WIT induces the transcriptional activities of BT, whereas long WIT depresses them, and the effect was blunted by Nrf2 knockout status. BT expression can be considered a surrogate marker for hepatic IRI.
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Affiliation(s)
- Joohyun Kim
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Alicia Martin
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Jennifer Yee
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lynn Fojut
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Aron M Geurts
- Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Kiyoko Oshima
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michael A Zimmerman
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Johnny C Hong
- Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.
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Ghinolfi D, Tincani G, Rreka E, Roffi N, Coletti L, Balzano E, Catalano G, Meli S, Carrai P, Petruccelli S, Biancofiore G, Filipponi F, De Simone P. Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study. Transpl Int 2018; 32:193-205. [PMID: 30198069 DOI: 10.1111/tri.13342] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 05/01/2018] [Accepted: 09/05/2018] [Indexed: 12/22/2022]
Abstract
Several risk factors for ischaemic-type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60-69 yo; 70-79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts ≥80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type-2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post-transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience.
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Affiliation(s)
- Davide Ghinolfi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Giovanni Tincani
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Erion Rreka
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Niccolo' Roffi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Laura Coletti
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Emanuele Balzano
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Gabriele Catalano
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Sonia Meli
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paola Carrai
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Stefania Petruccelli
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Gianni Biancofiore
- Anesthesia and Critical Care Medicine, University of Pisa Medical School Hospital, Pisa, Italy
| | - Franco Filipponi
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
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Cold Ischemia Time as a Factor in Post-transplantation Complications for Orthotopic Hepatic Transplantation. Transplant Proc 2018; 50:637-639. [PMID: 29579874 DOI: 10.1016/j.transproceed.2017.11.054] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 10/18/2017] [Accepted: 11/11/2017] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aims to compare a shorter cold ischemia time with the present one in relation to the complications developed in liver transplantations. DESIGN This is a retrospective, observational study of orthotopic liver transplantations performed with grafts from brain-dead donors during 12 months at a University Hospital (Seville). We compare incidence rates of complications (reperfusion syndrome, arterial and biliary complications, and prostaglandin requirements) between two groups according to cold ischemia times (group A < 6 hours; group B > 6 hours). RESULTS Sixty cases were included. There were more males in both groups as donors (55.5%) and recipients (75%). The median age was higher in group B in two cases. The Model for End-stage Liver Disease score was higher in patients with a shorter cold ischemia time, with a median of 20 hours (range, 16 to 26.5 hours). We observed that reperfusion syndrome (3.4% vs. 13.3%; P = .353), vascular complications (6.9% vs. 24.1%; P = .144), biliary tract complications (13.8% vs. 20.7%; P = .730), and prostaglandin requirements (3.4% vs. 20.7%; P = .102) were more common in group B, although without reaching statistical significance. After uni- and multivariate analyses, cold ischemia time longer than 6 hours was the only risk factor to develop complications (odds ratio: 3.578; 95% confidence interval: 1.125 to 11.374, P = .031). CONCLUSION According to the results of our analysis, cold ischemia times longer than 6 hours, as tends to be the usual procedure in most centers, imply higher rates of complications after liver transplantation.
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Ghinolfi D, Lai Q, Pezzati D, De Simone P, Rreka E, Filipponi F. Use of Elderly Donors in Liver Transplantation: A Paired-match Analysis at a Single Center. Ann Surg 2018; 268:325-331. [PMID: 28549011 DOI: 10.1097/sla.0000000000002305] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome. SUMMARY BACKGROUND DATA Use of livers from very old donors could expand the donor pool but is not universally implemented. METHODS This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18-69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases). RESULTS The median (interquartile range [IQR]) follow-up was 5.0 (2.0-8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6-2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0-1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0-1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03-2.13; P = 0.036). CONCLUSIONS Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted.
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Affiliation(s)
- Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Tuscany, Italy
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47
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Lindenmeyer CC, Kim A, Sanghi V, Lopez R, Niyazi F, Mehta NA, Flocco G, Kapoor A, Carey WD, Romero-Marrero C. The EMALT Score: An Improved Model for Prediction of Early Mortality in Liver Transplant Recipients. J Intensive Care Med 2018; 35:781-788. [PMID: 29996705 DOI: 10.1177/0885066618784869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE Needs, risks, and outcomes of patients admitted to a post liver transplant intensive care unit (POLTICU) differ in important ways from those admitted to pretransplant intensive care units (ICUs). The aim of this study was to create the optimal model to risk stratify POLTICU patients. METHODS Consecutive patients who underwent first deceased donor liver transplantation (LT) at a large United States center between 2008 and 2014 were followed from admission to LT and to discharge or death. Receiver-operating characteristic analysis was performed to assess the value of various scores in predicting in-hospital mortality. A predictive model was developed using logistic regression analysis. RESULTS A total of 697 patients underwent LT, and 3.2% died without leaving the hospital. A model for in-hospital mortality was derived from variables available within 24 hours of admission to the POLTICU. Key variables best predicting survival were white blood cell count, 24-hour urine output, and serum glucose. A model using these variables performed with an area under the curve (AUC) of 0.88, compared to the Acute Physiology and Chronic Health Evaluation III and Model for End-Stage Liver Disease, which performed with AUCs of 0.74 and 0.60, respectively. CONCLUSION An improved model, the early mortality after LT (EMALT) score, performs better than conventional models in predicting in-hospital mortality after LT.
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Affiliation(s)
| | - Ahyoung Kim
- Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Vedha Sanghi
- Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Rocio Lopez
- Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Fadi Niyazi
- Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Neal A Mehta
- Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Gianina Flocco
- Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Aanchal Kapoor
- Critical Care Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - William D Carey
- Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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48
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Rao F, Yang J, Gong C, Huang R, Wang Q, Shen J. Systematic review of preservation solutions for allografts for liver transplantation based on a network meta-analysis. Int J Surg 2018; 54:1-6. [PMID: 29684666 DOI: 10.1016/j.ijsu.2018.04.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/09/2018] [Accepted: 04/12/2018] [Indexed: 01/20/2023]
Abstract
AIMS The aim of this work was to determine the best preservation solutions for allografts for liver transplantation by quantitative network meta-analysis. METHODS Global electronic databases including PubMed, EMBASE, and Cochrane Library were searched for relevant randomized controlled trials. Seven pieces of parametric data were extracted from included studies for pooled estimation. A consistency model was used for direct and indirect comparisons. The cumulative probability P value was utilized to rank the solutions. A node-splitting model was utilized for testing the consistency of final data. Quality of evidence was assessed using the GRADE (Grades of Recommendations Assessment, Development and Evaluation) system. RESULTS Eleven 2-arm trials including 1319 patients and 5 different solutions were finally included. HTK (Histidine-tryptophan-ketoglutarate) solution exhibited the best efficacy for decreasing the primary dysfunction rate, biliary complications and ICU-stay time (probability P = 0.43, 0.45 and 0.58, respectively). Celsior solution significantly decreased the rate of rejection and early retransplantation (probability P = 0.73 and 0.38, respectively), and enhanced patient and graft survival (probability P = 0.90 and 0.98, respectively) more than did other solutions. Overall, the quality of evidence was rated high or moderate. CONCLUSIONS We suggested that HTK solution may offer the best safety during the perioperative period. However, Celsior solution led to better graft tolerance and exhibited greater benefit for long-term outcomes. And our conclusions still need to be further validated.
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Affiliation(s)
- Fengying Rao
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Jian Yang
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Cheng Gong
- Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China
| | - Rong Huang
- School of Nursing, Huanggang Polytechnic College, Huanggang, 438002, PR China
| | - Qi Wang
- The 1st Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, PR China.
| | - Jun Shen
- Emergency Center, Zhongnan Hospital of Wuhan University, 430071, Hubei Province, PR China.
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49
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Memeo R, de'Angelis N, Salloum C, Compagnon P, Laurent A, Feray C, Duvoux C, Azoulay D. Clinical outcomes of right-lobe split-liver versus orthotopic liver transplants from donors more than 70 years old. Prog Transplant 2018; 25:243-50. [PMID: 26308784 DOI: 10.7182/pit2015303] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Context-The imbalance between the organ supply and the number of potential transplant recipients led to consideration of expanded-criteria liver donors. Objective-To compare right-lobe split-liver transplants (RL-SLTs) with orthotopic liver transplants (OLTs) from donors more than 70 years old (OLT-O) and OLTs from donors less than 55 years old (OLT-Y). Methods-Seventy-one patients who received an RL-SLT were matched for age, sex, and Model for End-stage Liver Disease score with 71 patients who underwent OLT-O and 142 patients who underwent OLT-Y. Clinical outcomes were compared between groups. Results-Longer operation time was associated with RL-SLT (P< .001) as well as more blood loss (P= .03) and transfusions (P= .05). Postoperative morbidity was less in the OLT-Y group, with a lower rate of grades III to IV Clavien-Dindo complication (30%), compared with values in OLT-O (52%) and RL-SLT (38%). Kaplan-Meier analysis demonstrated better 1-year and 3-year survival rates in the OLT-Y group (97% and 92%, respectively), compared with 92% and 86.3%, respectively, in the RL-SLT group; and 84.5% and 73%, respectively, in the OLT-O group (P = .03). Kaplan-Meier analysis also demonstrated differences between the groups in terms of 1-year and 3-year graft survival rates, which were 92% and 86%, respectively, in OLT-Y; 77% and 66%, respectively, in the OLT-O, and 84.2% and 76.6%, respectively, in the RL-SLT group (P= .01). Conclusion-Even if OLT-Y guarantees better patient and graft survival, both RL-SLT and OLT-O can be used safely to expand the pool of liver donors, showing acceptable clinical results and complications rates.
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Affiliation(s)
- Riccardo Memeo
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Nicola de'Angelis
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Chady Salloum
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Philipe Compagnon
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Alexis Laurent
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Cyrille Feray
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Cristoph Duvoux
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Daniel Azoulay
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
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50
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González-Sánchez MR, Cascales-Campos PA, López-Espín JJ, Febrero B, Pons JA, Vargas Acosta A, Ros J, Sánchez-Bueno F, Robles R, Sáenz L, Ramírez P, Parilla P. Donors Older Than 75 Years Do Not Influence the Appearance of Biliary Complications After Liver Transplantation. Transplant Proc 2018; 50:640-643. [PMID: 29579875 DOI: 10.1016/j.transproceed.2017.11.048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 10/21/2017] [Accepted: 11/11/2017] [Indexed: 01/14/2023]
Abstract
BACKGROUND In recent years, several studies have shown that the age of the donor may be related to an increase in the occurrence of biliary complications (BCs), which remain the main cause of morbidity after liver transplantation. This study analyzed the type and management of these BCs, the impact of BCs on graft and patient survival rates, and the influence of some characteristics of donors and recipients on BC appearance in patients transplanted with donors 75 years of age or older. PATIENTS AND METHODS From 2003 to 2016, 100 liver transplantations with donors 75 years of age or older (15.6%) were performed in our hospital. The data were compared with a control group of 400 patients with younger donors (case-control 1:4 per chronology). RESULTS The BC rate in the group of patients transplanted with organs from elderly donors was 18%, compared to 21.5% in the control group. Specifically, in the immediate post-transplantation period, 14% of the elderly donor group and 13.8% of the control group presented some BCs, with no statistically significant differences in the incidence, type, and treatment of BCs between the two groups. The occurrence of BCs was not a factor associated with graft and patient survival rates. In the global population, donor death by cerebral vascular accident and male donors have influenced the occurrence of BCs. CONCLUSIONS The advanced age of the donor has not influenced BC rates after transplantation.
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Affiliation(s)
- M R González-Sánchez
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain.
| | - P A Cascales-Campos
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - J J López-Espín
- Operation Research Institute, University of Miguel Hernández, Elche, Spain
| | - B Febrero
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - J A Pons
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - A Vargas Acosta
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - J Ros
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - F Sánchez-Bueno
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - R Robles
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - L Sáenz
- Clinical Analysis Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - P Ramírez
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
| | - P Parilla
- Transplant Unit, General Surgery, Virgen de la Arrixaca University Hospital, Instituto Murciano de Investigaciones Biomédicas (IMIB), Murcia, Spain
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