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Balogh J, Mubashir T, Li Y, Digbeu BD, Hegde N, Pour FM, Rezapour M, Lai HY, West K, Chaudhry RA, Williams GW, Maroufy V. Effect of frailty as measured by functional impairment on long-term outcomes in liver transplantation in the United States. World J Transplant 2025; 15:98228. [DOI: 10.5500/wjt.v15.i2.98228] [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: 06/28/2024] [Revised: 10/08/2024] [Accepted: 12/09/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND In patients with chronic liver disease or hepatic dysfunction with sarcopenia, there is an increased risk of frailty as measured by functional impairment, making frailty a vital predictor of post-transplant mortality.
AIM To investigate the effects of frailty on mortality after liver transplantation.
METHODS A retrospective review of post-transplant outcomes in liver transplant recipients assessed frailty using Karnofsky Performance Score. Data from the Scientific Registry of Transplant Recipients database for 37427 liver transplant recipients was used.
RESULTS Of 82.7% frail patients, 42.7% were severely frail and 40% were moderately frail (P < 0.001) at the time of transplantation. Compared with non-frail patients, post-transplant mortality in frail patients was significantly higher at 12 months [odds ratio (OR) = 1.94, P = 0.02)]. Secondary analysis of the data revealed that liver grafts from donation after circulatory death (DCD) were more likely to be associated with frail patients at transplant (OR = 1.86, P < 0.001). Furthermore, a donor history of hypertension was associated with a lower likelihood of frailty in the recipient at the time of transplant (OR = 0.65, P = 0.03).
CONCLUSION Recipient frailty is associated with increased mortality at 12 months following liver transplantation, and liver transplants from donors with DCD are associated with increased frailty of the liver transplant recipient.
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Affiliation(s)
- Julius Balogh
- Department of CV Anesthesia, CHI St. Vincent Infirmary, Little Rock, AR 72205, United States
| | - Talha Mubashir
- Department of CV Anesthesia, CHI St. Vincent Infirmary, Little Rock, AR 72205, United States
| | - Yuan Li
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Biai D Digbeu
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Nikita Hegde
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, United States
| | - Fatemeh Movaghari Pour
- Department of Comprehensive Dentistry, UT Health San Antonio School of Dentistry, San Antonio, TX 78229, United States
| | | | - Hong-Yin Lai
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
| | - Kelly West
- Department of Anesthesiology, Critical Care and Pain Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, United States
| | - Rabail A Chaudhry
- Department of Anesthesiology and Pain Medicine, University of Arizona College of Medicine-Tucson, Tucson, AZ 85724, United States
| | - George W Williams
- Department of Anesthesiology, Critical Care and Pain Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, United States
| | - Vahed Maroufy
- Department of Biostatistics and Data Science, The University of Texas Health Center at Houston School of Public Health, Houston, TX 77030, United States
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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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Lindemann J, Yu J, Doyle MM. Normothermic machine perfusion for liver transplantation: current state and future directions. Curr Opin Organ Transplant 2024; 29:186-194. [PMID: 38483109 DOI: 10.1097/mot.0000000000001141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2024]
Abstract
PURPOSE OF REVIEW The number of patients on the liver transplant waitlist continues to grow and far exceeds the number of livers available for transplantation. Normothermic machine perfusion (NMP) allows for ex-vivo perfusion under physiologic conditions with the potential to significantly increase organ yield and expand the donor pool. RECENT FINDINGS Several studies have found increased utilization of donation after cardiac death and extended criteria brain-dead donor livers with implementation of NMP, largely due to the ability to perform viability testing during machine perfusion. Recently, proposed viability criteria include lactate clearance, maintenance of perfusate pH more than 7.2, ALT less than 6000 u/l, evidence of glucose metabolism and bile production. Optimization of liver grafts during NMP is an active area of research and includes interventions for defatting steatotic livers, preventing ischemic cholangiopathy and rejection, and minimizing ischemia reperfusion injury. SUMMARY NMP has resulted in increased organ utilization from marginal donors with acceptable outcomes. The added flexibility of prolonged organ storage times has the potential to improve time constraints and transplant logistics. Further research to determine ideal viability criteria and investigate ways to optimize marginal and otherwise nontransplantable liver grafts during NMP is warranted.
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Affiliation(s)
- Jessica Lindemann
- Department of Surgery, Section of Abdominal Organ Transplantation, Washington University School of Medicine, Saint Louis, Missouri, USA
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Hayasaka K, Ohkouchi S, Saito-Koyama R, Suzuki Y, Okazaki K, Sekine H, Watanabe T, Motohashi H, Okada Y. Aging exacerbates murine lung ischemia-reperfusion injury by excessive inflammation and impaired tissue repair response. Am J Transplant 2024; 24:293-303. [PMID: 37734444 DOI: 10.1016/j.ajt.2023.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/02/2023] [Accepted: 09/10/2023] [Indexed: 09/23/2023]
Abstract
Donor shortage is a major problem in lung transplantation (LTx), and the use of lungs from elderly donors is one of the possible solutions in a rapidly aging population. However, the utilization of organs from donors aged >65 years has remained infrequent and may be related to a poor outcome. To investigate the molecular events in grafts from elderly donors early after LTx, the left lungs of young and old mice were subjected to 1 hour of ischemia and subsequent reperfusion. The left lungs were collected at 1 hour, 1 day, and 3 days after reperfusion and subjected to wet-to-dry weight ratio measurement, histological analysis, and molecular biological analysis, including RNA sequencing. The lungs in old mice exhibited more severe and prolonged pulmonary edema than those in young mice after ischemia reperfusion, which was accompanied by upregulation of the genes associated with inflammation and impaired expression of cell cycle-related genes. Apoptotic cells increased and proliferating type 2 alveolar epithelial cells decreased in the lungs of old mice compared with young mice. These factors could become conceptual targets for developing interventions to ameliorate lung ischemia-reperfusion injury after LTx from elderly donors, which may serve to expand the old donor pool.
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Affiliation(s)
- Kazuki Hayasaka
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Shinya Ohkouchi
- Department of Occupational Health, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.
| | - Ryoko Saito-Koyama
- Department of Anatomic Pathology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan; Department of Pathology, National Hospital Organization, Sendai Medical Center, Sendai, Miyagi, Japan.
| | - Yamato Suzuki
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Keito Okazaki
- Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Hiroki Sekine
- Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Tatsuaki Watanabe
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Hozumi Motohashi
- Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
| | - Yoshinori Okada
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.
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Tingle SJ, Bramley R, Goodfellow M, Thompson ER, McPherson S, White SA, Wilson CH. Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study. Transplantation 2023; 107:2533-2544. [PMID: 37069657 DOI: 10.1097/tp.0000000000004610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2023]
Abstract
BACKGROUND Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor "liver blood tests" on transplant outcomes. METHODS This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019); adjusted regressions models were used to assess the effect of donor "liver blood tests" on outcomes. RESULTS A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044). CONCLUSIONS Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.
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Affiliation(s)
- Samuel J Tingle
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Rebecca Bramley
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Michael Goodfellow
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Emily R Thompson
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Stuart McPherson
- Department of Hepatology, Freeman Hospital, Newcastle upon Tyne, United Kingdom
| | - Steve A White
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Colin H Wilson
- National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, United Kingdom
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
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Barrett M, Sonnenday CJ. CAQ Corner: Deceased donor selection and management. Liver Transpl 2023; 29:1234-1241. [PMID: 37560989 DOI: 10.1097/lvt.0000000000000242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/31/2023] [Indexed: 08/11/2023]
Affiliation(s)
- Meredith Barrett
- University of Michigan, Department of Surgery, Section of Transplantation
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7
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Lee DU, Ponder R, Sandlow S, Yoo A, Lee KJ, Chou H, Fan GH, Urrunaga NH. The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis. Dig Liver Dis 2023; 55:1242-1252. [PMID: 37085440 PMCID: PMC10524091 DOI: 10.1016/j.dld.2023.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/05/2023] [Accepted: 03/25/2023] [Indexed: 04/23/2023]
Abstract
BACKGROUND & AIMS In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). METHODS The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. RESULTS There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n = 1581), those with gender-mismatch (male donors, n = 769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n = 304), no associations were found between gender-mismatch (female donors, n = 108) and all-cause mortality or graft failure. CONCLUSION This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.
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Affiliation(s)
- David Uihwan Lee
- Division of Gastroenterology and Hepatology, University of Maryland, 620W Lexington St, Baltimore, MD 21201, USA.
| | - Reid Ponder
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Sarah Sandlow
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Ashley Yoo
- Division of Gastroenterology and Hepatology, University of Maryland, 620W Lexington St, Baltimore, MD 21201, USA
| | - Ki Jung Lee
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Harrison Chou
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Gregory Hongyuan Fan
- Department of Medicine, Tufts University School of Medicine, Washington St, Boston, MA 02111, USA
| | - Nathalie Helen Urrunaga
- Division of Gastroenterology and Hepatology, University of Maryland, 620W Lexington St, Baltimore, MD 21201, USA
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Kim JM, Joo DJ, Hong SK, You YK, Hwang S, Ryu JH, Kim DJ, Yu HC, Nah YW, Kim MS. Outcomes of sexagenarian living liver donors in Korea: A multicenter study. Liver Transpl 2023; 29:698-710. [PMID: 36825584 DOI: 10.1097/lvt.0000000000000104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 01/10/2023] [Indexed: 02/25/2023]
Abstract
The safety of elderly living liver donors and recipient outcomes are always of concern. In the present study, the effects of age in 2 donor groups, a 60+years old group and a 50-59 years old group (referred to as the 60s and 50s donor groups, respectively), on living donor liver transplantation were compared regarding donor safety and recipient outcomes. We retrospectively identified 209 patients 50 years and above of age at 9 centers from 2005 to 2017 in Korea. The 60s donor group represented 10% (n=21) of donor patients. One case in each group was a left liver graft, respectively, and the others were right liver grafts. Postoperative complications were more common in the 60s donor group, but the proportion of Clavien-Dindo grade III in the 60s donor group did not differ from that in the 50s donor group. In-hospital mortality did not occur among donors, and donor mortality was not reported during the observation period. Postoperative total bilirubin and hospitalization in recipients of the 60s donor group were higher and longer than in recipients of the 50s donor group, respectively. Although the cumulative overall survival of the recipients in the 60s donor group was significantly lower than that of the 50s donor group, a difference was not observed in graft survival. Multivariate analysis showed that increased living liver donors age, the coexistence of HCC, and increased intraoperative blood loss during the recipient operation were important predisposing factors for patient death. Present study suggests that highly selected elderly living donors (≥60 y) can safely donate with similar recipient graft survival rates though the recipient overall patient survival is inferior compared to the 50s donor group.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, Seoul, Republic of Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, Republic of Korea
| | - Doo Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Li J, Lu H, Zhang J, Li Y, Zhao Q. Comprehensive Approach to Assessment of Liver Viability During Normothermic Machine Perfusion. J Clin Transl Hepatol 2023; 11:466-479. [PMID: 36643041 PMCID: PMC9817053 DOI: 10.14218/jcth.2022.00130] [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: 03/20/2022] [Revised: 06/14/2022] [Accepted: 08/10/2022] [Indexed: 01/18/2023] Open
Abstract
Liver transplantation is the most effective treatment of advanced liver disease, and the use of extended criteria donor organs has broadened the source of available livers. Although normothermic machine perfusion (NMP) has become a useful tool in liver transplantation, there are no consistent criteria that can be used to evaluate the viability of livers during NMP. This review summarizes the criteria, indicators, and methods used to evaluate liver viability during NMP. The shape, appearance, and hemodynamics of the liver can be analyzed at a macroscopic level, while markers of liver injury, indicators of liver and bile duct function, and other relevant indicators can be evaluated by biochemical analysis. The liver can also be assessed by tissue biopsy at the microscopic level. Novel methods for assessment of liver viability are introduced. The limitations of evaluating liver viability during NMP are discussed and suggestions for future clinical practice are provided.
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Affiliation(s)
| | | | | | | | - Qiang Zhao
- Correspondence to: Qiang Zhao, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. ORCID: https://orcid.org/0000-0002-6369-1393. Tel: +86-15989196835, E-mail:
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10
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Donor Noradrenaline Support Is Not Associated with Decreased Survival in Heart Transplant Recipients. J Clin Med 2022; 11:jcm11247271. [PMID: 36555888 PMCID: PMC9781589 DOI: 10.3390/jcm11247271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/30/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Objective: Although the application of higher doses of norepinephrine (NE) in potential organ donors is a frequent reason for heart decline, its associations with outcomes after heart transplantation (HTx) are discussed controversially. Therefore, we aimed to explore donor NE support’s potential impact on outcomes in our single-center heart transplant cohort. Methods: All patients who had undergone HTx in our center between September 2010 and April 2022 (n = 241) were screened for eligibility. From those, all patients with complete data on donor NE support (n = 238) were included. Recipients were divided into three groups according to their donor NE support: without support (n = 26), with low support of 0.01−0.2 µg/kg/min (n = 132), and with high support of > 0.2 µg/kg/min (n = 80). Receiver operating characteristics (ROC) and Kaplan Meier analysis was used to investigate the association of donor NE support and mortality after heart transplantation. Recipient and donor variables, including peri- and postoperative characteristics, were reviewed and compared. Results: NE support in donors ranged between 0 and 2.94 µg/kg/min (median 0.13 µg/kg/min, IQR 0.05−0.26 µg/kg/min). No association between donor NE support and mortality after HTx was observed (AUC for overall survival 0.494). Neither Kaplan-Meier analysis in survival up to 5 years after transplantation (Log Rank p = 0.284) nor group comparisons showed significant differences between the groups. With few exceptions, baseline characteristics in recipients and donors were comparable between the groups. Regarding peri- and postoperative parameters, increasing donor NE support was associated with a longer duration of mechanical ventilation (68 h and 95 h vs. 47 h), longer postoperative IMC/ICU stay (14 vs. 15 vs. 19 days), and a higher need for mechanical life support post-HTx (26% and 39% vs. 12%). Conclusion: In this retrospective analysis, NE support in donors prior to heart transplantation was unrelated to differing survival after heart transplantation. However, higher doses of donor NE were associated with prolonged ventilation, longer duration on IMC/ICU, and a higher need for extracorporeal life support in recipients post-HTx.
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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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Oehler D, Böttger C, Immohr MB, Bruno RR, Haschemi J, Scheiber D, Horn P, Aubin H, Tudorache I, Westenfeld R, Akhyari P, Kelm M, Lichtenberg A, Boeken U. Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit. Life (Basel) 2022; 12:1053. [PMID: 35888141 PMCID: PMC9325071 DOI: 10.3390/life12071053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 07/10/2022] [Accepted: 07/10/2022] [Indexed: 11/17/2022] Open
Abstract
Prolonged treatment of organ donors in the intensive care unit (ICU) may be associated with complications influencing the outcome after heart transplantation (HTx). We therefore aim to explore the potential impact of the donor length of stay (LOS) in the ICU on outcomes in our cohort. We included all patients undergoing HTx in our center between September 2010 and April 2022 (n = 241). Recipients were divided around the median into three groups regarding their donor LOS in the ICU: 0 to 3 days (≤50th percentile, n = 92), 4 to 7 days (50th-75th percentile, n = 80), and ≥8 days (≥75th percentile, n = 69). Donor LOS in the ICU ranged between 0 and 155 days (median 4, IQR 3-8 days). No association between the LOS in the ICU and survival after HTx was observed (AUC for overall survival 0.514). Neither the Kaplan-Meier survival analysis up to 5 years after HTx (Log-Rank p = 0.789) nor group comparisons showed significant differences. Baseline recipient characteristics were comparable between the groups, while the donor baselines differed in some parameters, such as less cardiopulmonary resuscitation prior to HTx in those with a prolonged LOS. However, regarding the recipients' peri- and postoperative parameters, the groups did not differ in all of the assessed parameters. Thus, in this retrospective analysis, although the donors differed in baseline parameters, the donor LOS in the ICU was not associated with altered recipient survival or outcome after HTx.
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Affiliation(s)
- Daniel Oehler
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Charlotte Böttger
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany;
| | - Moritz Benjamin Immohr
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
| | - Raphael Romano Bruno
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Jafer Haschemi
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Daniel Scheiber
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Patrick Horn
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Hug Aubin
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
| | - Igor Tudorache
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
| | - Ralf Westenfeld
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Payam Akhyari
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
| | - Malte Kelm
- Division of Cardiology, Pulmonology and Vascular Medicine Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (R.R.B.); (J.H.); (D.S.); (P.H.); (R.W.); (M.K.)
| | - Artur Lichtenberg
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
| | - Udo Boeken
- Department of Cardiac Surgery, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany; (M.B.I.); (H.A.); (I.T.); (P.A.); (A.L.)
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13
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Roesel MJ, Sharma NS, Schroeter A, Matsunaga T, Xiao Y, Zhou H, Tullius SG. Primary Graft Dysfunction: The Role of Aging in Lung Ischemia-Reperfusion Injury. Front Immunol 2022; 13:891564. [PMID: 35686120 PMCID: PMC9170999 DOI: 10.3389/fimmu.2022.891564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/21/2022] [Indexed: 01/14/2023] Open
Abstract
Transplant centers around the world have been using extended criteria donors to remedy the ongoing demand for lung transplantation. With a rapidly aging population, older donors are increasingly considered. Donor age, at the same time has been linked to higher rates of lung ischemia reperfusion injury (IRI). This process of acute, sterile inflammation occurring upon reperfusion is a key driver of primary graft dysfunction (PGD) leading to inferior short- and long-term survival. Understanding and improving the condition of older lungs is thus critical to optimize outcomes. Notably, ex vivo lung perfusion (EVLP) seems to have the potential of reconditioning ischemic lungs through ex-vivo perfusing and ventilation. Here, we aim to delineate mechanisms driving lung IRI and review both experimental and clinical data on the effects of aging in augmenting the consequences of IRI and PGD in lung transplantation.
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Affiliation(s)
- Maximilian J Roesel
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.,Institute of Medical Immunology, Charité Universitaetsmedizin Berlin, Berlin, Germany
| | - Nirmal S Sharma
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, United States.,Department of Medicine, Harvard Medical School, Boston, MA, United States
| | - Andreas Schroeter
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.,Regenerative Medicine and Experimental Surgery, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Tomohisa Matsunaga
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.,Department of Urology, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Hao Zhou
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Stefan G Tullius
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
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14
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Misar A, McLin VA, Calinescu AM, Wildhaber BE. Impact of length of donor ICU stay on outcome of patients after pediatric liver transplantation with whole and ex situ split liver grafts. Pediatr Transplant 2022; 26:e14186. [PMID: 34738698 DOI: 10.1111/petr.14186] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 09/22/2021] [Accepted: 10/19/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Patients who have a prolonged stay in the intensive care unit (ICU) are often excluded for organ donation because of supposed deleterious effects of a lengthy ICU stay. We aimed to determine the effects of a prolonged donor stay in the ICU on the outcome of liver transplantation (LT) in children. METHODS Retrospective review of 89 pediatric LT patients, age 0-18 years, period 2003-2018, including patients having undergone whole organ or in situ split LT. The patients were divided into two groups according to the donor length of stay in the ICU. A prolonged stay was defined as >5 days. Recipient, graft, and donor characteristics were compared; outcome parameters included recipient and graft survival rates and postoperative complications. RESULTS Group short (donor ICU stay <5 days) included 75 patients, group long (donor ICU stay >5 days) 14 patients. Baseline characteristics between recipients did not differ. Donors in group long had significantly more infectious complications and a higher gamma glutamyl transferase (gGT) the day of organ recovery. Incidence of biliary complications post-LT was significantly higher in group long (p = .029). Patient and graft survival rates did not differ significantly between groups. CONCLUSIONS Donors with a prolonged stay in the ICU should still be considered for liver donation if they fulfill most other selection criteria. Recipients from donors having stayed in ICU >5 days may be at increased risk of biliary complications.
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Affiliation(s)
- Aline Misar
- Pediatric Surgery Unit, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University Center of Pediatric Surgery of Western Switzerland, University of Geneva, Geneva, Switzerland
| | - Valerie A McLin
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University of Geneva, Geneva, Switzerland
| | - Ana M Calinescu
- Pediatric Surgery Unit, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University Center of Pediatric Surgery of Western Switzerland, University of Geneva, Geneva, Switzerland
| | - Barbara E Wildhaber
- Pediatric Surgery Unit, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University Center of Pediatric Surgery of Western Switzerland, University of Geneva, Geneva, Switzerland
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15
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Sadeghi F, Ramezani M, Beigee FS, Shadnia S, Moghaddam HH, Zamani N, Erfan Talab Evini P, Rahimi M. Organ Procurement From Poisoned Patients: A 14-Year Survey in 2 Academic Centers. EXP CLIN TRANSPLANT 2021; 20:520-525. [PMID: 34546157 DOI: 10.6002/ect.2021.0259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Organ transplant from poisoned donors is an issue that has received much attention, especially over the past decade. Unfortunately, there are still opponents to this issue who emphasize that toxins and drugs affect the body's organs and do not consider organs from poisoned donors appropriate for transplantation. MATERIALS AND METHODS Cases of brain death due to poisoning were collected from 2 academic centers in Tehran, Iran during a period from 2006 to 2020. Donor information and recipient condition at 1 month and 12 months after transplant and the subsequent transplant success rates were investigated. RESULTS From 102 poisoned donors, most were 30 to 40 years old (33.4%) and most were men (55.9%). The most common causes of poisoning among donors were opioids (28.4%). Six candidate donors had been referred with cardiorespiratory arrest; these patients had organs that were in suitable condition, and transplant was successful. Acute kidney injury was seen in 30 donors, with emergency dialysis performed in 23 cases. For 51% of donors, cardiopulmonary resuscitation was performed. The most donated organs were the liver (81.4%), left kidney (81.4%), and right kidney (80.4%). Survival rate of recipients at 1 month and 12 months was 92.5% and 91.4%, respectively. Graft rejection rate at 1 month and 12 months after transplant was 0.7% and 2.21%, respectively. CONCLUSIONS Organ donation from poisoning-related brain deaths is one of the best sources of organ supply for people in need. If the organ is in optimal condition before transplant, there are no exclusions for use of the graft.
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Affiliation(s)
- Farangis Sadeghi
- From the School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Martins PN, Rizzari MD, Ghinolfi D, Jochmans I, Attia M, Jalan R, Friend PJ. Design, Analysis, and Pitfalls of Clinical Trials Using Ex Situ Liver Machine Perfusion: The International Liver Transplantation Society Consensus Guidelines. Transplantation 2021; 105:796-815. [PMID: 33760791 DOI: 10.1097/tp.0000000000003573] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Recent trials in liver machine perfusion (MP) have revealed unique challenges beyond those seen in most clinical studies. Correct trial design and interpretation of data are essential to avoid drawing conclusions that may compromise patient safety and increase costs. METHODS The International Liver Transplantation Society, through the Special Interest Group "DCD, Preservation and Machine Perfusion," established a working group to write consensus statements and guidelines on how future clinical trials in liver perfusion should be designed, with particular focus on relevant clinical endpoints and how different techniques of liver perfusion should be compared. Protocols, abstracts, and full published papers of clinical trials using liver MP were reviewed. The use of a simplified Grading of Recommendations Assessment, Development, and Evaluation working group (GRADE) system was attempted to assess the level of evidence. The working group presented its conclusions at the International Liver Transplantation Society consensus conference "DCD, Liver Preservation, and Machine Perfusion" held in Venice, Italy, on January 31, 2020. RESULTS Twelve recommendations were proposed with the main conclusions that clinical trials investigating the effect of MP in liver transplantation should (1) make the protocol publicly available before the start of the trial, (2) be adequately powered, and (3) carefully consider timing of randomization in function of the primary outcome. CONCLUSIONS There are issues with using accepted primary outcomes of liver transplantation trials in the context of MP trials, and no ideal endpoint could be defined by the working group. The setup of an international registry was considered vital by the working group.
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Affiliation(s)
- Paulo N Martins
- Division of Organ Transplantation, Department of Surgery, University of Massachusetts Memorial Hospital, University of Massachusetts, Worcester, MA
| | - Michael D Rizzari
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI
| | - Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Tuscany, Italy
| | - Ina Jochmans
- Transplantation Research Group, Lab of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Belgium
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Magdy Attia
- Department of Hepatobiliary & Transplantation Surgery, Leeds Teaching Hospitals Trust, Leeds, United Kingdom
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, London, United Kingdom
| | - Peter J Friend
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
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17
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Ziogas IA, Martins PN, Alexopoulos SP, Matsuoka LK, Rauf MA, Geevarghese SK, Gorden LD, Karp SJ, Perkins JD, Montenovo MI. Effect of Donor Transaminase Levels on Graft Survival Following Liver Transplant: An Analysis of the Organ Procurement and Transplantation Network Database. EXP CLIN TRANSPLANT 2021; 19:250-258. [PMID: 33605200 DOI: 10.6002/ect.2020.0023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Despite data showing equivalent outcomes between grafts from marginal versus standard criteria deceased liver donors, elevated donor transaminases constitute a frequent reason to decline potential livers. We assessed the effect of donor transaminase levels and other characteristics on graft survival. MATERIALS AND METHODS We performed a retrospective cohort analysis of adult first deceased donor liver transplant recipients with available transaminase levels registered in the Organ Procurement and Transplantation Network database (2008-2018). We used Cox proportional hazards regression to determine the effects of donor characteristics on graft survival. RESULTS Of 53 913 liver transplants, 52 158 were allografts from donors with low transaminases (≤ 500 U/L; group A) and 1755 were from donors with elevated transaminases (> 500 U/L; group B). Group A recipients were more likely to be hospitalized (P = .01) or in intensive care (P < .001) or to have mechanical assistance (P < .001), portal vein thrombosis (P = .01), diabetes mellitus (P = .003), or dialysis the week before liver transplant (P = .004). Multivariable analysis (controlling for recipient characteristics) showed donor risk factors of graft failure included diabetes mellitus (P < .001), donation after cardiac death (P < .001), total bilirubin > 3.5 mg/dL (P < .001), serum creatinine > 1.5 mg/dL (P = .01), and cold ischemia time > 6 hours (P < .001). Regional organ sharing showed lower risk of graft failure (P = .02). Donor transaminases > 500 U/L were not associated with graft failure (relative risk, 1.02; 95% CI, 0.91-1.14; P = .74). CONCLUSIONS Donor transaminases > 500 U/L should not preclude the use of liver grafts. Instead, donor total bilirubin > 3.5 mg/dL and serum creatinine > 1.5 mg/dL appear to be associated with higher likelihood of graft failure after liver transplant.
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Affiliation(s)
- Ioannis A Ziogas
- From the Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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18
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Kadohisa M, Inomata Y, Uto K, Hayashida S, Ohya Y, Yamamoto H, Sugawara Y, Hibi T. Impact of Donor Age on the Outcome of Living-donor Liver Transplantation: Special Consideration to the Feasibility of Using Elderly Donors. Transplantation 2021; 105:328-337. [PMID: 32235254 DOI: 10.1097/tp.0000000000003246] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND The use of elderly donors (≥60 y) in living-donor liver transplantation (LDLT) remains controversial. In this study, we aimed to determine the safety of surgery for elderly donors and the impact of donor age on LDLT outcomes. METHODS We, retrospectively, reviewed 470 cases of LDLT at Kumamoto University Hospital from December 1998 to March 2017. RESULTS Donors were divided into 5 groups according to age: 20-29 (n = 109), 30-39 (n = 157), 40-49 (n = 87), 50-59 (n = 81), and ≥60 (n = 36). At our institution, elderly donor candidates required additional preoperative work-up. There were no significant differences in the incidence of postoperative complications and duration of postoperative hospital stay among the 5 donor groups. Regardless of graft type, elderly donors were comparable to younger donor groups (<30 y) in postoperative recovery of liver function. Risk-adjusted overall survival rates of recipients among donor groups were not significantly different. Additionally, donor age was not significantly associated with 6-month graft survival of adult and pediatric recipients. CONCLUSIONS Elderly candidates ≥60 years of age can safely be selected as LDLT donors after meticulous preoperative work-up.
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Affiliation(s)
- Masashi Kadohisa
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | | | - Keiichi Uto
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | - Shintaro Hayashida
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | - Yuki Ohya
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | - Hidekazu Yamamoto
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | - Yasuhiko Sugawara
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
| | - Taizo Hibi
- Department of Transplantation and Pediatric Surgery, Kumamoto University, Kumamoto, Japan
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19
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Impact of donor sodium levels on clinical outcomes in liver transplant recipients: a systematic review. Eur J Gastroenterol Hepatol 2020; 32:1489-1496. [PMID: 32804851 DOI: 10.1097/meg.0000000000001776] [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] [Indexed: 12/10/2022]
Abstract
We performed a systematic review of the literature to examine the effects of donor sodium levels on liver graft function and recipient survival, as well as to identify the optimal serum sodium target in donors. We searched MEDLINE, Cochrane, and trial registries from 1946 to May 2019 for studies that evaluated the effect of serum sodium levels in neurologically deceased liver donors on transplant outcomes. We used a two-step review process with four independent reviewers to identify relevant articles based on inclusion/exclusion criteria. We summarize the results narratively, assess the risk of bias, and apply the Grading of Recommendations Assessment, Development, and Evaluation methods to evaluate the certainty in the evidence. We included 25 cohort studies were in our final analysis (total n = 19 389). Twenty-two reported on graft function and survival. Summary data suggest an association between donor serum sodium and recipient liver graft dysfunction, with very low certainty in evidence due to serious concerns with risk of bias, inconsistency, indirectness, and imprecision. Seven studies reported on recipient mortality, with results suggesting no association between donor sodium and recipient survival. The certainty in evidence for this outcome was also very low due to serious concerns with imprecision, indirectness, and risk of bias. Donor sodium dysregulation is associated with liver graft dysfunction, but not recipient mortality. Further research is needed to determine the effects of correcting donor sodium levels on transplant outcomes, quantify the dose-response curve, and identify liver recipients most vulnerable to sodium dysregulation.
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20
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Improvement in Liver Transplant Outcomes From Older Donors: A US National Analysis. Ann Surg 2020; 270:333-339. [PMID: 29958229 DOI: 10.1097/sla.0000000000002876] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate trends in long-term graft and patient outcomes following liver transplantation using grafts from donors ≥60 years old. SUMMARY BACKGROUND DATA The scarcity of donor livers has led to increased utilization of organs from donors ≥60 years old. However, few studies have examined how long-term transplant outcomes from older donors have evolved over time. METHODS The OPTN/UNOS database was queried for all first-time isolated adult liver transplants. We identified 14,796 adult liver transplant using donors ≧60-year-old suitable for analysis from 1990 to 2014. Cohorts were then developed based on 5-year intervals of transplant date. Kaplan-Meier analysis was used to compare graft and patient survival for recipients from older donor across each 5-year era. RESULTS Utilization of donor grafts ≥60 years old increased steadily for the first 15 years of the study, but has leveled off over the last 10 years. Comparison of the earliest and latest eras in the study was notable for an increase in median recipient age (51 vs. 59, P < 0.001) and reduction in median cold ischemic time (10 vs. 6 h, P = 0.001). Unadjusted 5-year graft and patient survival has improved significantly over time (P < 0.0001). More importantly, the discrepancy in survival between older and younger grafts has narrowed substantially over time (P < 0.0001). CONCLUSIONS This study demonstrates significant improvement in transplant outcomes with donor grafts ≥60-years old and supports increased but judicious use of extended criteria donors liver grafts. Improved patient selection and reduction in cold ischemia time appear to be contributing factors.
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21
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Martins PN, Rawson A, Movahedi B, Brüggenwirth IMA, Dolgin NH, Martins AB, Mahboub P, Bozorgzadeh A. Single-Center Experience With Liver Transplant Using Donors With Very High Transaminase Levels. EXP CLIN TRANSPLANT 2019; 17:498-506. [DOI: 10.6002/ect.2017.0172] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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22
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Mojtabaee M, Ghorbani F, Nikeghbalian S, Fischer-Fröhlich CL, Sadegh-Beigee F. Liver Procurement from Poisoned Donors: A Survival Study. EXP CLIN TRANSPLANT 2019; 18:334-338. [PMID: 31104626 DOI: 10.6002/ect.2018.0339] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Although transplant teams understand the effects of donor characteristics on liver transplant outcomes, few studies have investigated the quality of livers obtained from poisoned donors. The aim of this study was to compare livers procured from poisoned donors with a matched control group. MATERIALS AND METHODS Liver transplant outcomes from poisoned donors and from donors with trauma-induced death (as the control group) were compared using data of an Organ Procurement Unit from 2000 to 2013. Procured livers were evaluated via histology findings before transplant. Recipient characteristics were assessed in both groups, and immediate and medium-term (up to 5 years after transplant) survival rates were compared with the use of Kaplan-Meier analyses and log-rank tests. RESULTS Over a 13-year organ donation program, 1485 livers from brain dead patients were donated. Among them, 115 poisoned donors were evaluated for liver grafts; of these, 74 successful liver transplants were performed. In the poisoned donors, the incidence of reversed cardiac arrest was 54.1%. Likewise, acute kidney injury was detected in 14.9% of the patients, and 16.2% needed urgent dialysis either for clearance of the toxic agents or for treatment of acute kidney injury. No significant differences were observed in 1- to 5-year survival rates, and log-rank test also showed a significance level of 0.83. CONCLUSIONS Proper case selection strategies can be implemented to expand the donor pool, including use of poisoned donors. Hence, poisoning is not a contra-indication for a referral, which could lead to decreased mortality for patients requiring a liver transplant.
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Affiliation(s)
- Meysam Mojtabaee
- From the Organ Procurement Unit, Lung Transplantation Research Center (LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
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A New Proposal of Criteria for the Future Remnant Liver Volume in Older Patients Undergoing Major Hepatectomy for Biliary Tract Cancer. Ann Surg 2019; 267:338-345. [PMID: 27849659 DOI: 10.1097/sla.0000000000002080] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To evaluate whether advanced age increases the risk of severe complications after major hepatectomy with bile duct resection (BDR) in patients with biliary tract cancer, and to establish new criteria for the percentage of the future remnant liver volume (%FLV) in older patients undergoing this operation. BACKGROUND Advanced age is reported to inhibit liver regeneration and suppress immune function; however, little is known about the risk of aging in high-stress surgery, such as biliary tract surgery. METHODS Consecutive patients who underwent major hepatectomy with BDR between 2000 and 2013 were retrospectively reviewed. Severe postoperative complications were defined as Clavien-Dindo grade ≥IV. RESULTS In 225 patients undergoing major hepatectomy with BDR, advanced age was significantly correlated with the incidence of severe postoperative complications, with cut-off value of 69 years. In comparing postoperative complications, the incidences of hyperbilirubinemia, liver failure, respiratory failure, sepsis, severe complications, and operation-related death were more frequent in the older group. Moreover, advanced age (≥69 years) was an independent risk factor associated with severe complications after major hepatectomy with BDR. Delayed liver regeneration was the reason for the age-related risks. The incidence of severe postoperative complications in older patients was significantly decreased if %FLV was set at ≥45%. CONCLUSIONS Advanced age is a strong independent risk factor for severe complications after major hepatectomy with BDR. To decrease the risk of advanced age, the minimum limit of %FLV for this operation should be set at ≥45% in patients aged ≥69 years.
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Kim SH, Park GC, Hwang S, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Cho HD, Kwon JH, Jung YK, Ha SM, Kang SH, Lee SG. Results of Adult Living Donor Liver Transplantation with Sixth-Decade Donors: A Propensity Score Matching Study in a High-Volume Institution. Ann Transplant 2018; 23:802-807. [PMID: 30442881 PMCID: PMC6251075 DOI: 10.12659/aot.911550] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND We assessed the prognostic impact of donor age on the outcome of adult living donor liver transplantation (LDLT). MATERIAL AND METHODS The study population comprised adult donor and recipients of right lobe grafts for LDLT performed from January 2005 to December 2016. There were 35 living donors aged ≥50 years (old-age donor group). As a control group, donors in their 20s (young-age donor group) were selected after one-to-one propensity score matching based on sex, model for end-stage liver disease (MELD) score, and primary diagnosis. RESULTS Donor age was 52.5±1.5 years versus 25.4±3.1 years in the old- and young-age donor groups, respectively. Remnant volumes of the 2 groups were 38.9±3.0% versus 38.1±2.9%, respectively (p=0.98). One-month regeneration rate of the remnant liver was 101.1±10.6% versus 104.5±11.8%, respectively (p=0.08), and there was no significant difference in the incidences of donor complications. Mean MELD score was 15 versus 14, respectively (p=0.82). Graft-to-recipient weight ratio was 1.02±0.43 versus 0.91±0.63, respectively (p=0.28). In the recipients, biliary complication occurred in 11.4% versus 8.6%, respectively (p=0.12), and there was no difference in 5-year survival rates of both groups (p=0.15). The 1-week and 1-month regeneration rates of the remnant left liver were 71.6±9.9% and 100.1±10.6% in the old-age group, respectively, whereas those were 80.2±12.1% and 104.5±11.8% in the young-age group, respectively (p=0.08). CONCLUSIONS Right lobe grafts from donors aged ≥50 years showed the usual recovery of graft function but rather delayed liver regeneration. Thus, old-aged donors should be selected prudently after consideration of hepatic resection rate, graft size, and hepatic steatosis.
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Affiliation(s)
- Seok-Hwan Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.,Department of Surgery, Chungnam National University Hospital, Daejeon, South Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ki-Hum Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hwi-Dong Cho
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae-Hyun Kwon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong-Kyu Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Su-Min Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang-Hyun Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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25
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A Donor Quality Index for liver transplantation: development, internal and external validation. Sci Rep 2018; 8:9871. [PMID: 29959344 PMCID: PMC6026153 DOI: 10.1038/s41598-018-27960-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 05/29/2018] [Indexed: 11/12/2022] Open
Abstract
Organ shortage leads to using non-optimal liver grafts. Thus, to determine the graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have been proposed. In a previous study we showed that neither could be validated on the French database. Our aim was then dedicated to propose an adaptive Donor Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in France between 2009 and 2013, with an external validation based on 1048 French LT performed in 2014. Using Cox models and three different methods of selection, we developed a new score and defined groups at risk. Model performance was assessed by means of three measures of discrimination corrected by the optimism using a bootstrap procedure. An external validation was also performed in order to evaluate its calibration and discrimination. Five donor covariates were retained: age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance, and liver type. Three groups at risk could be discriminated. The performances of the model were satisfactory after internal validation. Calibration and discrimination were preserved in the external validation dataset. The DQI exhibited good properties and is potentially adaptive as an aid for better guiding decision making for LT.
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Freitas ACTD, Matos DDMND, Milsted JAT, Coelho JCU. EFFECTS OF COLD ISCHEMIA TIME ON HEPATIC ALLOGRAFT FUNCTION. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2018; 30:239-243. [PMID: 29340545 PMCID: PMC5793139 DOI: 10.1590/0102-6720201700040003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 08/10/2017] [Indexed: 01/16/2023]
Abstract
BACKGROUND Cold ischemia time is related to success of liver transplantation. AIM To compare the impact of cold ischemia time on allografts locally collected to those collected distantly. METHODS Were evaluated 83 transplantations. The patients were divided in two groups: those who received liver grafts collected from cities out of Curitiba (n=42) and locally (n=41). From the donors were compared: cause of death, days at ICU, cardiac arrest, vasoactive drugs, lab exams, gender, age, and BMI. Were compared the subsequent information of receptors: cold ischemia time, warm ischemia time, length of surgery, lab exams, etiology of cirrhosis, MELD score, age, gender, histology of graft, use of vasoactive drugs, and blood components transfusion. Were evaluated the correlation between cold ischemia time and lab results. RESULTS The liver grafts collected from other cities were submitted to a longer cold ischemia time (500±145 min) compared to those locally collected (317,85±105 min). Donors from other cities showed a higher serum sodium level at donation (154±16 mEq/dl) compared to those from Curitiba (144±10 mEq/dl). The length of cold ischemia time was related to serum levels of ALT and total bilirubin. CONCLUSION Liver grafts distantly collected underwent longer cold ischemia times, although it caused neither histologic injuries nor higher transfusion demands. There is a correlation between cold ischemia time and hepatic injury, translated by elevation of serum ALT and total bilirubin levels.
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Affiliation(s)
| | | | | | - Julio Cezar Uili Coelho
- Clinical Hospital Complex, Hepatic Transplantation Service.,Faculty of Medicine, Federal University of Paraná, Curitiba, PR, Brazil
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Hu Z, Mei S, Xiang J, Zhou J, Li Z, Zhou L, Yan S, Wang W, Zheng S. Survival rates after liver transplantation using hypertensive donor grafts: an analysis of the Scientific Registry of Transplant Recipients database. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:441-448. [PMID: 28544515 DOI: 10.1002/jhbp.466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The use of grafts from donors with hypertension (HTN) in liver transplantation has grown rapidly recently, but whether HTN donors affect post-liver transplantation survival is unclear. METHODS We used data from the Scientific Registry of Transplant Recipients database (2004-2008), and evaluated differences in baseline characteristics and outcomes between recipients of grafts from HTN and non-HTN donors. Kaplan-Meier and multivariate Cox regression models were used in assessing patient survival. RESULTS We identified 8,411 recipients of HTN donor grafts (33.2%) and 16,891 (66.8%) recipients of non-HTN donor grafts. Graft and patient survival rates were significantly lower in recipients of HTN donor grafts versus non-HTN donor grafts (1-year, 3-year, and 5-year graft survival rates of 75%, 64%, 50% vs. 80%, 72%, 62% [P < 0.001], respectively, and patient survival rates of 79%, 69%, 56% vs. 83%, 75%, 65% [P < 0.001], respectively). A history of HTN >5 years was also associated with lower rates of graft and patient survival (P < 0.001). A HTN donor was independently associated with a higher risk of graft loss (hazard ratio 1.10, 95% confidence interval 1.01-1.18). CONCLUSION The present study shows that graft and patient survivals were lower in recipients of hypertensive donor grafts, and highlights the importance of appropriately screening donors for HTN.
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Affiliation(s)
- Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Shengmin Mei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Jie Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Zhiwei Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China
| | - Lin Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
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Actual Risk of Using Very Aged Donors for Unselected Liver Transplant Candidates: A European Single-center Experience in the MELD Era. Ann Surg 2017; 265:388-396. [PMID: 28059967 DOI: 10.1097/sla.0000000000001681] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To evaluate the whole experience of liver transplantation (LT) with donors ≥70 years in a single center not applying specific donor/recipient matching criteria. BACKGROUND LT with very old donors has historically been associated with poorer outcomes. With the increasing average donor age and the advent of Model for End-stage Liver Diseases (MELD) score-based allocation criteria, an optimal donor/recipient matching is often unsuitable. METHODS Outcomes of all types of LTs were compared according to 4 study groups: patients transplanted between 1998 and 2003 with donors <70 (group 1, n = 396) or ≥70 years (group 2, n = 88); patients transplanted between 2004 and 2010 with donors <70 (group 3, n = 409), or ≥70 years (group 4, n = 190). From 2003, graft histology was routinely available before cross-clamping, and MELD-driven allocation was adopted. RESULTS Groups 1 and 2 were similar for main donor and recipient variables, and surgical details. Group 4 had shorter donor ICU stay, lower rate of moderate-to-severe graft macrosteatosis (2.3% vs 8%), and higher recipient MELD score (22 vs 19) versus group 3. After 2003, median donor age, recipient age, and MELD score significantly increased, whereas moderate-to-severe macrosteatosis and ischemia time decreased. Five-year graft survival was 63.6% in group 1 versus 59.1% in group 2 (P = 0.252) and 70.9% in group 3 versus 67.6% in group 4 (P = 0.129). Transplants performed between 1998 and 2003, recipient HCV infection, balance of risk score >18, and pre-LT renal replacement treatments were independently associated with worse graft survival. CONCLUSIONS Even without specific donor/recipient matching criteria, the outcomes of LT with donors ≥70 and <70 years are comparable with appropriate donor management.
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Organ donor management: Eight common recommendations and actions that deserve reflection. Med Intensiva 2017; 41:559-568. [PMID: 28318674 DOI: 10.1016/j.medin.2017.01.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 01/11/2017] [Accepted: 01/13/2017] [Indexed: 01/18/2023]
Abstract
Despite major advances in our understanding of the physiopathology of brain death (BD), there are important controversies as to which protocol is the most appropriate for organ donor management. Many recent reviews on this subject offer recommendations that are sometimes contradictory and in some cases are not applied to other critically ill patients. This article offers a review of the publications (many of them recent) with an impact upon these controversial measures and which can help to confirm, refute or open new areas of research into the most appropriate measures for the management of organ donors in BD, and which should contribute to discard certain established recommendations based on preconceived ideas, that lead to actions lacking a physiopathological basis. Aspects such as catecholamine storm management, use of vasoactive drugs, hemodynamic objectives and monitoring, assessment of the heart for donation, and general care of the donor in BD are reviewed.
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30
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Das S, Swain SK, Addala PK, Balasubramaniam R, Gopakumar CV, Zirpe D, Renganathan K, Kollu H, Patel D, Vibhute BB, Rao PS, Krishnan E, Gopasetty M, Khakhar AK, Vaidya A, Ramamurthy A. Initial Poor Function and Primary Nonfunction in Deceased-Donor Orthotopic Liver Transplantation Maintaining Short Cold Ischemic Time. Prog Transplant 2016; 26:340-347. [PMID: 27543202 DOI: 10.1177/1526924816663516] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Nations with emerging deceased-donor liver transplantation programs, such as India, face problems associated with poor donor maintenance. Cold ischemic time (CIT) is typically maintained short by matching donor organ recovery and recipient hepatectomy to achieve maximum favorable outcome. We analyzed different extended criteria donor factors including donor acidosis, which may act as a surrogate marker of poor donor maintenance, to quantify the risk of primary nonfunction (PNF) or initial poor function (IPF). METHODS A single-center retrospective outcome analysis of prospectively collected data of patients undergoing deceased-donor liver transplantation over 2 years to determine the impact of different extended criteria donor factors on IPF and PNF. RESULTS From March 2013 to February 2015, a total of 84 patients underwent deceased-donor liver transplantation. None developed PNF. Thirteen (15.5%) patients developed IPF. Graft macrosteatosis and donor acidosis were only related to IPF ( P = .002 and P = .032, respectively). Cold ischemic time was maintained short (81 cases ≤8 hours, maximum 11 hours) in all cases. CONCLUSION Poor donor maintenance as evidenced by donor acidosis and graft macrosteatosis had significant impact in developing IPF when CIT is kept short. Similar study with larger sample size is required to establish extended criteria cutoff values.
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Affiliation(s)
- Somak Das
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Sudeepta Kumar Swain
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Pavan Kumar Addala
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | | | - C V Gopakumar
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Dinesh Zirpe
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | | | - Harsha Kollu
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Darshan Patel
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Bipin B Vibhute
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Prashantha S Rao
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Elankumaran Krishnan
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Mahesh Gopasetty
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Anand K Khakhar
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
| | - Anil Vaidya
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India.,3 Oxford Division of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Anand Ramamurthy
- 1 Gastrointestinal Surgery and Liver Transplantation, Apollo Hospital, Chennai, India
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The Kupffer Cell Number Affects the Outcome of Living Donor Liver Transplantation from Elderly Donors. Transplant Direct 2016; 2:e94. [PMID: 27819035 PMCID: PMC5082997 DOI: 10.1097/txd.0000000000000608] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Accepted: 06/03/2016] [Indexed: 01/09/2023] Open
Abstract
Background There have been no previous reports how Kupffer cells affect the outcome of living donor liver transplantation (LDLT) with an elderly donor. The aim of this study was to elucidate the influence of Kupffer cells on LDLT. Methods A total of 161 adult recipients underwent LDLT. The graft survival, prognostic factors for survival, and graft failure after LDLT were examined between cases with a young donor (<50, n = 112) and an elderly donor (≥50, N = 49). The Kupffer cells, represented by CD68-positive cell in the graft, were examined in the young and elderly donors. Results In a multivariable analysis, a donor older than 50 years, sepsis, and diabetes mellitus were significant predictors of graft failure after LDLT. The CD68 in younger donors was significantly more expressed than that in elderly donors. The group with a less number of CD68-positive cells in the graft had a significantly poor survival in the elderly donor group and prognostic factor for graft failure. Conclusions The worse outcome of LDLT with elderly donors might be related to the lower number of Kupffer cells in the graft, which can lead to impaired recovery of the liver function and may predispose patients to infectious diseases after LDLT.
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Rebolledo RA, Hoeksma D, Hottenrott CMV, Bodar YJL, Ottens PJ, Wiersema-Buist J, Leuvenink HGD. Slow induction of brain death leads to decreased renal function and increased hepatic apoptosis in rats. J Transl Med 2016; 14:141. [PMID: 27193126 PMCID: PMC4872359 DOI: 10.1186/s12967-016-0890-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/29/2016] [Indexed: 11/17/2022] Open
Abstract
Background Donor brain death (BD) is an independent risk factor for graft survival in recipients. While in some patients BD results from a fast increase in intracranial pressure, usually associated with trauma, in others, intracranial pressure increases more slowly. The speed of intracranial pressure increase may be a possible risk factor for renal and hepatic graft dysfunction. This study aims to assess the effect of speed of BD induction on renal and hepatic injury markers. Methods BD induction was performed in 64 mechanically ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Rats were observed for 0.5, 1, 2 or 4 h following BD induction. Slow induction was achieved by inflating the balloon-catheter at a speed of 0.015 ml/min until confirmation of BD. Fast induction was achieved by inflating the balloon at 0.45 ml/min for 1 min. Plasma, kidney and liver tissue were collected for analysis. Results Slow BD induction led to higher plasma creatinine at all time points compared to fast induction. Furthermore, slow induction led to increased renal mRNA expression of IL-6, and renal MDA values after 4 h of BD compared to fast induction. Hepatic mRNA expression of TNF-α, Bax/Bcl-2, and protein expression of caspase-3 was significantly higher due to slow induction after 4 h of BD compared to fast induction. PMN infiltration was not different between fast and slow induction in both renal and hepatic tissue. Conclusion Slow induction of BD leads to poorer renal function compared to fast induction. Renal inflammatory and oxidative stress markers were increased. Liver function was not affected by speed of BD induction but hepatic inflammatory and apoptosis markers increased significantly due to slow induction compared to fast induction. These results provide initial proof that speed of BD induction influences detrimental renal and hepatic processes which could signify different donor management strategies for patients progressing to BD at different speeds.
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Affiliation(s)
- Rolando A Rebolledo
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. .,Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
| | - Dane Hoeksma
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Christina M V Hottenrott
- Department of Cardiothoracic Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Yves J L Bodar
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Petra J Ottens
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Janneka Wiersema-Buist
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Henri G D Leuvenink
- Department of Surgery, University Medical Center Groningen, University of Groningen, CMC V, Y2144, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
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Ferla F, Mariani A, di Sandro S, Buscemi V, Lauterio A, Mangoni J, Covucci E, Giacomoni A, De Carlis L. Do Older Liver Grafts Have Worse Survival? The Niguarda Experience. Transplant Proc 2016; 48:362-365. [PMID: 27109956 DOI: 10.1016/j.transproceed.2015.12.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/30/2015] [Indexed: 01/14/2023]
Abstract
BACKGROUND Elderly donor livers are thought to be marginal graft. In the present study, we aimed to identify an age threshold to consider a graft as elderly to identify the trend (if any) of the donor age in our series and to identify an efficient allocation criteria for elderly grafts. METHODS We reviewed in a retrospective manner our series of 1520 liver transplants, comparing graft survival under and over a certain age. On the basis of the results of this analysis, we identified a threshold of 70 years to define a graft as old. The donor age trend analysis showed an increasing rate of transplants from elderly donors. RESULTS To identify efficient allocation criteria for elderly graft, we stratified the series by the disease of the recipient: 556 patients underwent transplants for hepatocellular carcinoma (HCC+ group) and 964 for other diseases (HCC- group). Two hundred twenty-one patients of 556 of the HCC+ group were hepatitis c virus (HCV) negative (HCC+/HCV- group), and 312 of 964 of the HCC- group were HCV positive (HCC-/HCV+). The survival analysis showed no significant differences in comparing the outcome for elderly and young grafts in the HCC+ (P = .135) and HCC- (P = .055) groups. CONCLUSIONS When comparing the survival of old and young livers in the HCC+/HCV- group, the elderly livers appear to have a better outcome (P = .05); on the other hand, the same analysis in the HCC-/HCV+ group shows a worse outcome for old-aged grafts (P = .026). Therefore, the present study suggests that elderly livers should be allocated to hepatocellular carcinoma (HCC) patients and should be avoided in HCV+ recipients.
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Affiliation(s)
- F Ferla
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy.
| | - A Mariani
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - S di Sandro
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - V Buscemi
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - A Lauterio
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - J Mangoni
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - E Covucci
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - A Giacomoni
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
| | - L De Carlis
- Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milano, Italy
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Westerkamp AC, Korkmaz KS, Bottema JT, Ringers J, Polak WG, van den Berg A, van Hoek B, Metselaar HJ, Porte RJ. Elderly donor liver grafts are not associated with a higher incidence of biliary complications after liver transplantation: results of a national multicenter study. Clin Transplant 2015; 29:636-43. [PMID: 25997000 DOI: 10.1111/ctr.12569] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2015] [Indexed: 01/08/2023]
Abstract
BACKGROUND Liver transplantation with livers grafts from elderly donors has been associated with a higher risk of biliary complications. The aim of this study was to examine whether our national protocol could contribute to a lower incidence of biliary complications. METHODS All adult recipients in the Netherlands transplanted with a liver from an elderly donor (≥ 65 yrs; n = 68) in the period January 2000-July 2011 were matched with recipients of a liver from a donor <65 yr (n = 136). Outcome parameters were 90-d, one-yr, and three-yr patient/graft survival rates, biliary complications (non-anastomotic stricture, anastomotic stricture, biliary leakage, and post-transplant cholangitis), and postoperative hepatic ischemic injury serum markers (AST/ALT). RESULTS The median cold ischemia time (CIT) was 7:25 (h:min) in the group recipients of an elderly donor liver graft. Ninety-day, one-yr, and three-yr patient/graft survival rates were similar between the group with an elderly donor liver and their younger controls. Moreover, no differences were found in the incidence of biliary complications and postoperative levels of AST/ALT between the two groups. CONCLUSION Transplantation of livers from elderly donors (≥ 65 yr) is not associated with a higher incidence of biliary complications, in a national policy wherein the CIT is kept short.
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Affiliation(s)
- Andrie C Westerkamp
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Kerem S Korkmaz
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jan T Bottema
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan Ringers
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Aad van den Berg
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Robert J Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Russolillo N, Ratti F, Viganò L, Langella S, Cipriani F, Aldrighetti L, Ferrero A. The Influence of Aging on Hepatic Regeneration and Early Outcome after Portal Vein Occlusion: A Case-Control Study. Ann Surg Oncol 2015; 22:4046-51. [PMID: 25758189 DOI: 10.1245/s10434-015-4478-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND Portal vein occlusion (PVO) is used to increase inadequate future liver remnant volume (FLRV). Impaired liver regeneration has been reported in aged animals. This study was designed to evaluate the impact of patient age on hepatic regeneration. METHODS Sixty patients aged ≥70 years were matched 1:1 with 60 patients aged <70 years. Matching criteria were sex, diabetes, cirrhosis, pre-PVO chemotherapy and bevacizumab administration, and jaundice. RESULTS The median ages in the older and younger groups were 76 (range 70-83) years and 59 (range 20-69) years, respectively (p < 0.001). Median FLRV following PVO (33.1 ± 6.8 vs. 31.9 ± 6.0 %) and volumetric increase (0.52 ± 0.35 vs. 0.49 ± 0.34) were similar in the two groups. Of the older and younger patients, 10 % and 1.7 %, respectively, did not undergo liver surgery after PVO (p = 0.051). Mortality (5.5 vs. 6.7 %) and major morbidity (25.9.8 vs. 22 %) rates were similar. Liver failure rate was higher in older patients (35.1 vs. 16.9 %, p < 0.026), mainly due to Grade A liver failure (20.3 vs. 8.4 %, p < 0.001). Multivariate analysis showed that age ≥ 70 years [odds ratio (OR) 3.03; 95 % confidence interval (CI) 1.18-7.78; p = 0.020] and biliary cancer diagnosis (OR 4.69; 95 % CI 1.81-12.09; p = 0.001) were independent risk factors for postoperative liver failure. CONCLUSIONS Liver regeneration after PVO is not impaired by age. Nevertheless, liver resection in elderly patients is performed less often after PVO and carries a higher risk of liver failure.
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Affiliation(s)
- Nadia Russolillo
- Department of General and Oncological Surgery, Ospedale Mauriziano "Umberto I", Turin, Italy.
| | - Francesca Ratti
- Liver Unit, Department of Hepatobiliary Surgery, San Raffaele Hospital, Milan, Italy
| | - Luca Viganò
- Liver Surgery Unit, Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Serena Langella
- Department of General and Oncological Surgery, Ospedale Mauriziano "Umberto I", Turin, Italy
| | - Federica Cipriani
- Liver Unit, Department of Hepatobiliary Surgery, San Raffaele Hospital, Milan, Italy
| | - Luca Aldrighetti
- Liver Unit, Department of Hepatobiliary Surgery, San Raffaele Hospital, Milan, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Ospedale Mauriziano "Umberto I", Turin, Italy
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Chedid MF, Rosen CB, Nyberg SL, Heimbach JK. Excellent long-term patient and graft survival are possible with appropriate use of livers from deceased septuagenarian and octogenarian donors. HPB (Oxford) 2014; 16:852-858. [PMID: 24467292 PMCID: PMC4159459 DOI: 10.1111/hpb.12221] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Accepted: 12/17/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although increasing donor age adversely affects survival after liver transplantation, livers have been used from selected deceased donors older than 70 years. Although there are reports of excellent short-term results, long-term results are unknown. Our experience was reviewed with septuagenarian and octogenarian deceased donors to determine long-term outcomes. METHODS All primary deceased donor liver transplants performed at our institution between July 1998 and December 2010 were reviewed. Recipients of livers procured after circulatory arrest, split and reduced-size livers and multiple organ transplants were excluded from the study. Patient and graft survival were calculated using the Kaplan-Meier method, and survival comparisons were made with the log-rank test. RESULTS In total, 780 patients met inclusion criteria, and 109 patients received livers from donors older than 70 years (range = 70-86). There were no differences in long-term patient (P = 0.67) or graft (P = 0.42) survival between hepatitis C negative recipients of livers from older compared with younger donors. In contrast, 7-year survival for HCV-positive recipients of older donor livers was less than half that of HCV-negative recipients. DISCUSSION Transplantation of livers from septua- and octogenarian donors can achieve excellent long-term patient and graft survival for selected HCV-negative patients.
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Affiliation(s)
- Marcio F Chedid
- Division of Transplantation Surgery, Department of Surgery and William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
| | - Charles B Rosen
- Division of Transplantation Surgery, Department of Surgery and William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
| | - Scott L Nyberg
- Division of Transplantation Surgery, Department of Surgery and William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
| | - Julie K Heimbach
- Division of Transplantation Surgery, Department of Surgery and William J. von Liebig Transplant Center, Mayo ClinicRochester, MN, USA
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Younossi ZM, Stepanova M, Saab S, Kalwaney S, Clement S, Henry L, Frost S, Hunt S. The impact of type 2 diabetes and obesity on the long-term outcomes of more than 85 000 liver transplant recipients in the US. Aliment Pharmacol Ther 2014; 40:686-94. [PMID: 25040315 DOI: 10.1111/apt.12881] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Revised: 06/25/2014] [Accepted: 06/27/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Type 2 diabetes is known to negatively impact the outcome of chronic liver disease. AIM To evaluate the impact of diabetes on the outcomes of liver transplants (LT). METHODS Study cohort included adults (>18 years) who received LT in the US between 1994 and 2013 (The Scientific Registry of Transplant Recipients). Pre- and post-transplant diabetes was recorded in patients with mortality follow-up. RESULTS We included 85 194 liver transplant recipients. Of those, 11.2% had history of pre-transplant diabetes. The most common indications for liver transplant were hepatitis C (36.4%), alcohol-related liver disease (20.6%), primary liver malignancy of unspecified aetiology (14.7%), cryptogenic cirrhosis (8.0%), hepatitis B (4.6%) and non-alcoholic steatohepatitis (3.9%). A total of 96.5% transplants were from deceased donors, and 7.9% donors had history of diabetes. During an average 6.5 years of follow-up, 31.3% recipients died and 8.8% had a graft failure. In multivariate survival analysis [at least 5 years of cohort follow-up (N = 35 870)], after adjustment for age, ethnicity, insurance type, history of chronic diseases, HCV infection and noncompliance, independent predictors of recipient mortality included the presence of pre-transplant diabetes [adjusted hazard ratio (95%CI) = 1.21 (1.12-1.30)] and developing diabetes post-transplant [1.06 (1.02-1.11)]. Donor's history of diabetes was also independently associated with higher mortality [1.10 (1.02-1.19)]. Furthermore, donor's history of diabetes was also associated with an increased the risk of liver graft failure [1.35 (1.24-1.47)]. CONCLUSIONS Presence of type 2 diabetes pre- and post-transplant, as well as presence of type 2 diabetes in the donors, are all associated with an increased risk of adverse post-transplant outcomes.
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Affiliation(s)
- Z M Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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Perez-Protto SE, Reynolds LF, Dalton JE, Taketomi T, Irefin SA, Parker BM, Quintini C, Sessler DI. Deceased donor hyperglycemia and liver graft dysfunction. Prog Transplant 2014; 24:106-12. [PMID: 24598573 DOI: 10.7182/pit2014737] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONTEXT Hyperglycemia is common in deceased donors, and provokes numerous adverse events in hepatocytic mitochondria. OBJECTIVE To determine whether hyperglycemia in deceased donors is associated with graft dysfunction after orthotopic liver transplant. METHODS Charts on 572 liver transplants performed at the Cleveland Clinic between January 2005 and October 2010 were reviewed. The primary measure was time-weighted averages of donors' glucose measurements. Liver graft dysfunction was defined as (1) primary nonfunction as indicated by death or retransplant or (2) liver graft dysfunction as indicated by an aspartate amino transferase level greater than 2000 U/L or prothrombin time greater than 16 seconds during the first postoperative week. The relationship of interest was estimated by using a multivariable logistic regression. RESULTS The incidence of graft dysfunction was 25%. No significant relationship was found between the range of donor glucose measurements and liver graft dysfunction after donor characteristics were adjusted for (P= .14, Wald test, adjusted odds ratio [95% CI] for liver graft dysfunction corresponding to a relative doubling in time-weighted average for donor glucose of 1.43 [0.89-2.30]). The results thus do not suggest that strict glucose control in donors is likely to improve graft quality.
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Routh D, Naidu S, Sharma S, Ranjan P, Godara R. Changing pattern of donor selection criteria in deceased donor liver transplant: a review of literature. J Clin Exp Hepatol 2013; 3:337-46. [PMID: 25755521 PMCID: PMC3940395 DOI: 10.1016/j.jceh.2013.11.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 11/18/2013] [Indexed: 02/06/2023] Open
Abstract
During the last couple of decades, with standardization and progress in surgical techniques, immunosuppression and post liver transplantation patient care, the outcome of liver transplantation has been optimized. However, the principal limitation of transplantation remains access to an allograft. The number of patients who could derive benefit from liver transplantation markedly exceeds the number of available deceased donors. The large gap between the growing list of patients waiting for liver transplantation and the scarcity of donor organs has fueled efforts to maximize existing donor pool and identify new avenues. This article reviews the changing pattern of donor for liver transplantation using grafts from extended criteria donors (elderly donors, steatotic donors, donors with malignancies, donors with viral hepatitis), donation after cardiac death, use of partial grafts (split liver grafts) and other suboptimal donors (hypernatremia, infections, hypotension and inotropic support).
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Key Words
- CIT, cold ischemia time
- DCD, donation after cardiac death
- DGF, delayed graft function
- ECD, extended criteria donor
- ECMO, extra corporeal membrane oxygenation
- HBIg, hepatitis B immune globulin
- HBV, hepatitis B virus
- HCV, hepatitis C virus
- HIV, human immunodeficiency virus
- HTLV, human T-lymphotropic virus
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MELD, Model for End-Stage Liver Disease
- NRP, normothermic regional perfusion
- PNF, primary nonfunction
- SLT, split liver transplantation
- SOFT, survival outcomes following liver transplantation
- SRTR, Scientific Registry of Transplant Recipients
- donor pool
- extended criteria donor
- liver transplantation
- mTOR, mammalian target of rapamycin inhibitors
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Affiliation(s)
- Dronacharya Routh
- Department of GI Surgery and Liver Transplantation, Army Hospital (R&R), New Delhi 110010, India
| | - Sudeep Naidu
- Department of GI Surgery and Liver Transplantation, Army Hospital (R&R), New Delhi 110010, India,Address for correspondence: Sudeep Naidu, Professor and Head, Department of GI Surgery and Liver Transplantation, Army Hospital (R&R), New Delhi 110010, India. Tel.: +91 (0) 9999454052.
| | - Sanjay Sharma
- Department of GI Surgery and Liver Transplantation, Army Hospital (R&R), New Delhi 110010, India
| | - Priya Ranjan
- Department of GI Surgery and Liver Transplantation, Army Hospital (R&R), New Delhi 110010, India
| | - Rajesh Godara
- Department of Surgery, Post Graduate Institute of Medical Sciences, Rhotak, Haryana, India
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Silberhumer GR, Rahmel A, Karam V, Gonen M, Gyoeri G, Kern B, Adam R, Muehlbacher F, Rogiers X, Burroughs AK, Berlakovich GA. The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience. Transpl Int 2013; 26:990-8. [PMID: 23931659 DOI: 10.1111/tri.12156] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 12/14/2012] [Accepted: 06/28/2013] [Indexed: 12/14/2022]
Abstract
Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
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Affiliation(s)
- Gerd R Silberhumer
- Department of Transplant Surgery, Medical University Vienna, Vienna, Austria
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Izamis ML, Berendsen T, Uygun K, Yarmush M. Addressing the Donor Liver Shortage withEX VIVOMachine Perfusion. JOURNAL OF HEALTHCARE ENGINEERING 2012. [DOI: 10.1260/2040-2295.3.2.279] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Tanemura A, Mizuno S, Wada H, Yamada T, Nobori T, Isaji S. Donor age affects liver regeneration during early period in the graft liver and late period in the remnant liver after living donor liver transplantation. World J Surg 2012; 36:1102-1111. [PMID: 22374540 DOI: 10.1007/s00268-012-1496-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The aim of the present study was to evaluate the influence of donor age on liver regeneration and surgical outcomes in recipients and donors. PATIENTS AND METHODS Among 101 cases of adult-to-adult living donor liver transplantation (LDLT) between March 2002 and March 2011, according to donor age: younger (Y) <50 years of age or older (O) ≥ 50 years of age, the donors and recipients using right (R) or left (L) graft were divided into groups Y/R (n = 51) and O/R (n = 17), and groups Y/L (n = 26) and O/L (n = 7), respectively. Remnant liver volume (RemLV) and graft liver volume (GLV) were estimated by computed tomography (CT) volumetry. A disintegrin and metalloprotease with thrombospondin type I domain 13 (ADAMTS13) activities and von Willebrand factor (vWF) antigen levels were measured as factors reflecting thrombotic microangiopathy. RESULTS Among the donors, RemLV/total liver volume (TLV) was lower in group O/R than in group Y/R, although there were no significant differences by t-test with the Bonferroni correction (rough p value = 0.02 at 6 months and rough p value > 0.05 at 1, 3, and 12 months). Donor age (≥ 50 years) was independently correlated with impaired remnant liver regeneration at 6 months in right lobe LDLT (p = 0.04). Among the recipients, GLV/standard liver volume (SLV) was lower during the first month, although there were no significant differences between the two groups by t-test with the Bonferroni correction (rough p value = 0.03 at 1 week and rough p value >0.05 at 2 weeks and 1 and 3 months). Donor age (≥ 50 years) was independently correlated with impaired graft liver regeneration at 1 week in both right and left lobe LDLT (p < 0.05). ADAMTS13 activities were lower in group O/R than in group Y/R, although there were no significant differences by t-test with the Bonferroni correction (rough p value = 0.049 on postoperative days (POD) 1 and 28 and rough p value >0.05 on POD 7 and 14). vWF/ADAMTW13 ratios were higher on POD 14, although there were no significant differences between the two groups by t-test with the Bonferroni correction (rough p value = 0.044 on POD 14 and rough p value >0.05 on POD 1, 7, 14, and 28). CONCLUSIONS The surgical outcomes using older donor livers for LDLT were comparable to those using younger donor livers. When using older donor livers, however, we should pay attention to the liver volume for recipients as well as donors, because older donor livers might have impaired regenerative ability.
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Affiliation(s)
- Akihiro Tanemura
- Department of Hepatobiliary-Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary-Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan.
| | - Hideo Wada
- Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Tomomi Yamada
- Department of Translational Medical Science, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Tsutomu Nobori
- Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
| | - Shuji Isaji
- Department of Hepatobiliary-Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan
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Abstract
Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores < 15 is associated with lower allograft survival; the use of the LDRI has limited this practice. Significant regional variations in donor quality, as measured by the LDRI, remain in the United States. We also review other potential indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival.
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Affiliation(s)
| | | | - Yi Peng
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, Minnesota
| | - Peter Stock
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Ray Kim
- Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Ajay K. Israni
- Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, Minnesota
- Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
- Department of Epidemiology & Community Health, University of Minnesota, Minneapolis, Minnesota
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Kim DY, Moon J, Island ER, Tekin A, Ganz S, Levi D, Selvaggi G, Nishida S, Tzakis AG. Liver transplantation using elderly donors: a risk factor analysis. Clin Transplant 2011; 25:270-6. [PMID: 20184629 DOI: 10.1111/j.1399-0012.2010.01222.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Survival after liver transplantation is negatively impacted by use of elderly deceased donors, but excluding them would increase waiting times and waiting list mortality. We reviewed our experience with liver transplantation (LT) utilizing livers from deceased donors 65 yr of age and older to identify those factors that impact graft survival. All adult patients (≥ 18 yr old) who underwent primary LT using deceased donor livers from donors aged ≥ 65 yr between February 1995 and November 2003 were included. With multivariate analysis we found four unfavorable characteristics significantly associated with higher post-transplant graft failure rate. These characteristics are hepatitis C as an etiology of liver disease, Model for End-Stage Liver Disease score >20, serum glucose level of donor > 200 mg/dL at the time of liver recovery, and skin incision to aortic cross-clamp time > 40 minutes in the donor surgery. The five-yr estimated graft survival rates having 0, 1, 2, 3, and 4 unfavorable characteristics were 100%, 82.0%, 81.7%, 39.3%, and 25.0%, respectively (p < 0.05). Our data demonstrated good graft survival can be achieved in LT using elderly donor liver allografts with appropriate patient selection, donor blood glucose management and efficient liver recovery with minimal manipulation of the liver during donor surgery.
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Affiliation(s)
- Dae Y Kim
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
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Ono Y, Kawachi S, Hayashida T, Wakui M, Tanabe M, Itano O, Obara H, Shinoda M, Hibi T, Oshima G, Tani N, Mihara K, Kitagawa Y. The influence of donor age on liver regeneration and hepatic progenitor cell populations. Surgery 2011; 150:154-61. [PMID: 21719061 DOI: 10.1016/j.surg.2011.05.004] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2011] [Accepted: 05/12/2011] [Indexed: 12/18/2022]
Abstract
BACKGROUND Recent reports suggest that donor age might have a major impact on recipient outcome in adult living donor liver transplantation (LDLT), but the reasons underlying this effect remain unclear. The aims of this study were to compare liver regeneration between young and aged living donors and to evaluate the number of Thy-1+ cells, which have been reported to be human hepatic progenitor cells. METHODS LDLT donors were divided into 2 groups (Group O, donor age ≥ 50 years, n = 6 and Group Y, donor age ≤ 30 years, n = 9). The remnant liver regeneration rates were calculated on the basis of computed tomography volumetry on postoperative days 7 and 30. Liver tissue samples were obtained from donors undergoing routine liver biopsy or patients undergoing partial hepatectomy for metastatic liver tumors. Thy-1+ cells were isolated and counted using immunomagnetic activated cell sorting (MACS) technique. RESULTS Donor liver regeneration rates were significantly higher in young donors compared to old donors (P = .042) on postoperative day 7. Regeneration rates were significantly higher after right lobe resection compared to rates after left lobe resection. The MACS findings showed that the number of Thy-1+ cells in the human liver consistently tended to decline with age. CONCLUSION Our study revealed that liver regeneration is impaired with age after donor hepatectomy, especially after right lobe resection. The declining hepatic progenitor cell population might be one of the reasons for impaired liver regeneration in aged donors.
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Affiliation(s)
- Yoshihiro Ono
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Eguchi S, Takatsuki M, Hidaka M, Soyama A, Muraoka I, Tomonaga T, Shimokawa I, Kanematsu T. Lack of grafted liver rejuvenation in adult-to-pediatric liver transplantation. Dig Dis Sci 2011; 56:1542-7. [PMID: 20936349 DOI: 10.1007/s10620-010-1445-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2010] [Accepted: 09/19/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND A grafted donor liver should grow and survive under the different conditions presented by a liver transplantation recipient. It has remained unclear, however, whether the age of a grafted liver can be modulated by recipient factors. AIMS This study investigated whether a grafted aged donor liver can be rejuvenated in a pediatric recipient. METHODS Of 119 living donor liver transplants, ten pairs were adult-to-pediatric combinations. Senescence marker protein-30 (SMP-30), which is a protein that is remarkably reduced upon aging, was used as a senescence marker. Immunohistochemical staining for SMP-30 was performed in biopsy specimen after living donor liver transplantation (LDLT). Re-expression of SMP-30 was investigated in a biopsied adult liver (n = 6) that had been transplanted in a pediatric recipient. RESULTS A remarkable expression of SMP-30 was seen in a control pediatric normal liver in comparison with that in an aged adult donor biopsy. Re-expression or an increase in SMP-30 was not observed in the liver of any pediatric recipient who had received an adult liver. CONCLUSION An adult grafted liver does not appear to rejuvenate in a pediatric recipient.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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Abstract
There are still many controversial aspects regarding which method is best for managing organ donors to prevent, lessen, or even reverse the organ alterations associated with brain death. Fundamental aspects are the management of an adequate perfusion pressure, hormone restoration, and opposition of the inflammatory state associated with brain death. Once volume has been normalized, it is necessary to administer vasoactive drugs, including catecholamines to re-establish the loss of sympathetic tone at the vascular and myocardial level. It is impossible to define the ideal or maximal catecholamine dose because it depends on the donor's vascular tone, vascular reactivity, and pharmacokinetic variability characteristic of critical patients, particularly organ donors. To control early onset of diabetes insipidus, it is necessary to administer desmopressin. At present there are insufficient clinical studies to show the usefulness of triiodothyronine. Furthermore, due to its limited availability, elevated cost, and probable side effects, the use of this hormone is not justified. More importance is being given to the negative influence of the inflammatory state associated with brain death, which has repercussions on organ viability and probably influences the prevalence of rejection episodes. Meanwhile in organ donor management, we recommend the use of 15 mg/kg of methylprednisolone as soon as possible. Contrary to triiodothyronine, the potential benefit of its immunomodulatory effects, its low cost, and the absence of major side effects justify this recommendation.
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Affiliation(s)
- C Chamorro
- Regional Transplant Coordinator, C/ Plaza Trias Bertran 7, 28020 Madrid, Spain.
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Abstract
PURPOSE OF REVIEW Despite improvements in respiratory care and lung transplant organ allocation algorithms, waiting lists continue to grow worldwide. Attempts at improving organ donation rates have generally had little impact on the increase in the number of transplants performed. Improved use of the available pool of cadaveric organ donors, therefore, represents one of few immediately available strategies to alleviate organ shortages. RECENT FINDINGS The once-strict lung donor selection criteria have, of necessity, been relaxed and, in many instances, this situation has been to no apparent detrimental effect on posttransplant outcome. There is, however, some evidence that extension of donor acceptability in some respects leads to poorer early outcomes, mainly by increasing the rate of early graft dysfunction. The extension of selection criteria to allow the maximum number of safe lung transplants, coupled with aggressive and appropriate donor management is, therefore, of particular current relevance to the lung transplantation community. SUMMARY Although the available evidence for and against the commonly used lung donor selection criteria leaves many questions unanswered, it can help decrease the large number of uncertainties that be falls the practice of lung donor selection and recipient matching.
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Timchenko NA. Aging and liver regeneration. Trends Endocrinol Metab 2009; 20:171-6. [PMID: 19359195 DOI: 10.1016/j.tem.2009.01.005] [Citation(s) in RCA: 161] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2008] [Revised: 01/14/2009] [Accepted: 01/15/2009] [Indexed: 12/12/2022]
Abstract
The loss of regenerative capacity is the most dramatic age-associated alteration in the liver. Although this phenomenon was reported over 50 years ago, the molecular basis for the loss of regenerative capacity of aged livers has not been fully elucidated. Aging causes alterations of several signal-transduction pathways and changes in the expression of CCAAT/enhancer-binding protein (C/EBP) and chromatin-remodeling proteins. Consequently, aging livers accumulate a multi-protein C/EBPalpha-Brm-HDAC1 complex that occupies and silences E2F-dependent promoters, reducing the regenerative capacity of livers in older mice. Recent studies have provided evidence for the crucial role of epigenetic silencing in the age-dependent inhibition of liver proliferation. This review focuses on mechanisms of age-dependent inhibition of liver proliferation and approaches for correcting liver regeneration in the elderly.
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Affiliation(s)
- Nikolai A Timchenko
- Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
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Gastaca M. Extended Criteria Donors in Liver Transplantation: Adapting Donor Quality and Recipient. Transplant Proc 2009; 41:975-9. [DOI: 10.1016/j.transproceed.2009.02.016] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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