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Paiano L, Azoulay D, Blandin F, Allard MA, Pietrasz D, Ciacio O, Pittau G, Salloum C, De Martin E, Sa Cunha A, Adam R, Cherqui D, Vibert E, Golse N. Split liver transplantation in high MELD score adult recipients: a reappraisal. HPB (Oxford) 2025:S1365-182X(25)00079-6. [PMID: 40133133 DOI: 10.1016/j.hpb.2025.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 03/02/2025] [Accepted: 03/06/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND Split liver transplantation (SLT) from deceased donors is a potential solution to the global organ shortage. While effective in patients with mild disease, outcomes in high MELD score recipients remain uncertain and conflicting. This study compares survival in high vs. low MELD score recipients. METHODS This retrospective single-centre study included all consecutive patients transplanted with a split liver graft between 2010 and 2022. Two groups of recipients with MELD<25 and ≥ 25 at LT were compared. RESULTS The study population included 119 patients (n = 98 with MELD<25, n = 21 with MELD≥25) with an average follow-up of 55 months. Both groups were comparable in terms of indication for transplantation and donor characteristics. The high MELD group required more blood transfusions (7 vs. 3 units; p < 0.001) during LT and had a longer stay in intensive care unit (7 vs. 5 days; p = 0.011). Biliary, arterial, and venous complications were similar between groups, as well as graft survival (5 years: 75 % vs. 61 %, p = 0.35) and long-term overall survival (5 years: 83 % vs. 75 %, p = 0.17). DISCUSSION Our results indicate that SLT for patients with MELD≥25 improves access to grafts, is feasible and safe, without significant increased risk of severe complications or decreased long-term overall patient or graft survivals.
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Affiliation(s)
- Lucia Paiano
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Daniel Azoulay
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | | | - Marc-Antoine Allard
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - Daniel Pietrasz
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - Oriana Ciacio
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Gabriella Pittau
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Chady Salloum
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Eleonora De Martin
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - Antonio Sa Cunha
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - René Adam
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France
| | - Daniel Cherqui
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - Eric Vibert
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France
| | - Nicolas Golse
- Hôpital Paul Brousse, Centre Hépato-Biliaire, AP-HP, Villejuif, France; Inserm, Université Paris-Saclay, UMRS 1193, Physio Pathogénèse et Traitement des Maladies du foie, FHU Hepatinov, 94800, Villejuif, France.
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Wehrle CJ, Maspero M, Pinna AD, Dutkowski P, Miller C, Hashimoto K, Clavien PA, Schlegel A. Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver? Ann Surg 2025; 281:485-495. [PMID: 38489660 DOI: 10.1097/sla.0000000000006259] [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: 03/17/2024]
Abstract
OBJECTIVE To assess factors affecting the cumulative lifespan of a transplanted liver. BACKGROUND Liver aging is different from other solid organs. It is unknown how old a liver can actually get after liver transplantation. METHODS Deceased donor liver transplants from 1988 to 2021 were queried from the United States UNOS registry. Cumulative liver age was calculated as donor age + recipient graft survival. RESULTS In total, 184,515 livers were included. Most were donation after brain death donors (n = 175,343). The percentage of livers achieving >70, 80, 90, and 100 years cumulative age was 7.8% (n = 14,392), 1.9% (n = 3576), 0.3% (n = 528), and 0.01% (n = 21), respectively. The youngest donor age contributing to a cumulative liver age >90 years was 59 years, with posttransplant survival of 34 years. In pediatric recipients, 736 (4.4%) and 282 livers (1.7%) survived >50 and 60 years overall, respectively. Transplanted livers achieved cumulative age >90 years in 2.86 per 1000 and >100 years in 0.1 per 1000. The U.S. population at large has a cumulative "liver age" >90 years in 5.35 per 1000 persons, and >100 years in 0.2 per 1000. Livers aged >60 years at transplant experienced both improved cumulative survival ( P < 0.0001) and interestingly improved survival after transplantation ( P < 0.0001). Recipient warm ischemia time of >30 minutes was most predictive of reduced cumulative liver survival overall (n = 184,515, hazard ratio = 1.126, P < 0.001) and excluding patients with mortality in the first 6 months (n = 151,884, hazard ratio = 0.973, P < 0.001). CONCLUSIONS In summary, transplanted livers frequently get as old as those in the average population despite ischemic-reperfusion-injury and immunosuppression. The presented results justify using older donor livers regardless of donation type, even in sicker recipients with limited options.
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Affiliation(s)
- Chase J Wehrle
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Marianna Maspero
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
- Department of Surgery, Upper GI Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Antonio D Pinna
- Department of Abdominal Transplantation, Cleveland Clinic Florida, Weston, FL
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Charles Miller
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Koji Hashimoto
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
| | - Pierre-Alain Clavien
- Department of Transplantation, Wyss Zurich, ETH Zurich, and University of Zurich, Switzerland
| | - Andrea Schlegel
- Department of Surgery, Transplantation Center, Digestive Disease Institute, Cleveland Clinic, OH
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, OH
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3
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Safi K, Pawlicka AJ, Pradhan B, Sobieraj J, Zhylko A, Struga M, Grąt M, Chrzanowska A. Perspectives and Tools in Liver Graft Assessment: A Transformative Era in Liver Transplantation. Biomedicines 2025; 13:494. [PMID: 40002907 PMCID: PMC11852418 DOI: 10.3390/biomedicines13020494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain-such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease-technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.
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Affiliation(s)
- Kawthar Safi
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | | | - Bhaskar Pradhan
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | - Jan Sobieraj
- 1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Andriy Zhylko
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
| | - Marta Struga
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
| | - Alicja Chrzanowska
- Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland; (K.S.)
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4
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Moosburner S, Patel MS, Wang BK, Prasadh J, Öllinger R, Lurje G, Sauer IM, Vagefi PA, Pratschke J, Raschzok N. Multinational Analysis of Marginal Liver Grafts Based on the Eurotransplant Extended Donor Criteria. Ann Surg 2024; 280:896-904. [PMID: 39140592 DOI: 10.1097/sla.0000000000006491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2024]
Abstract
OBJECTIVE To evaluate the outcome of marginal liver grafts based on the Eurotransplant extended criteria donor (ECD) criteria. BACKGROUND Eurotransplant uses a broad definition of ECD criteria (age >65 years, steatosis >40%, body mass index >30 kg/m 2 , intensive care unit stay >7 days, donation after circulatory death, and certain laboratory parameters) for allocating organs to recipients who have consented to marginal grafts. Historically, marginal liver grafts were associated with increased rates of dysfunction. METHODS Retrospective cohort analysis using the German Transplant Registry and the U.S. Scientific Registry of Transplant Recipients (SRTR) from 2006 to 2016. Results were validated with recent SRTR data (2017-2022). Donors were classified according to the Eurotransplant ECD criteria, donation after circulatory death was excluded. Data were analyzed with cutoff prediction, binomial logistic regression, and multivariate Cox regression. RESULTS The study analyzed 92,330 deceased brain-dead donors (87% SRTR) and 70,374 transplants (87% SRTR) in adult recipients. Predominant ECD factors were donor age in Germany (30%) and body mass index in the United States (28%). Except for donor age, grafts meeting ECD criteria were not associated with impaired 1 or 3-year survival. Cutoffs had little to no predictive value for 30-day graft survival (area under the receiver operating curve: 0.49-0.52) and were nominally higher for age (72 vs 65 years) in Germany as compared with those defined by current Eurotransplant criteria. CONCLUSIONS The outcome of transplanted grafts from higher risk donors was nearly equal to standard donors with Eurotransplant criteria failing to predict survival of marginal grafts. Modifying ECD criteria could improve graft allocation and potentially expand the donor pool.
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Affiliation(s)
- Simon Moosburner
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Madhukar S Patel
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, TX
| | - Benjamin K Wang
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, TX
| | - Jai Prasadh
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, TX
| | - Robert Öllinger
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Georg Lurje
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Igor M Sauer
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Parsia A Vagefi
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, TX
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Nathanael Raschzok
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- BIH Biomedical Innovation Academy, BIH Charité Clinician Scientist Program, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
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5
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Gómez-Gavara C, Bilbao I, Piella G, Vazquez-Corral J, Benet-Cugat B, Pando E, Molino JA, Salcedo MT, Dalmau M, Vidal L, Esono D, Cordobés MÁ, Bilbao Á, Prats J, Moya M, Dopazo C, Mazo C, Caralt M, Hidalgo E, Charco R. Enhanced Artificial Intelligence Methods for Liver Steatosis Assessment Using Machine Learning and Color Image Processing: Liver Color Project. Clin Transplant 2024; 38:e15465. [PMID: 39382065 DOI: 10.1111/ctr.15465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 08/02/2024] [Accepted: 09/08/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND The use of livers with significant steatosis is associated with worse transplantation outcomes. Brain death donor liver acceptance is mostly based on subjective surgeon assessment of liver appearance, since steatotic livers acquire a yellowish tone. The aim of this study was to develop a rapid, robust, accurate, and cost-effective method to assess liver steatosis. METHODS From June 1, 2018, to November 30, 2023, photographs and tru-cut needle biopsies were taken from adult brain death donor livers at a single university hospital for the study. All the liver photographs were taken by smartphones then color calibrated, segmented, and divided into patches. Color and texture features were then extracted and used as input, and the machine learning method was applied. This is a collaborative project between Vall d'Hebron University Hospital and Barcelona MedTech, Pompeu Fabra University, and is referred to as LiverColor. RESULTS A total of 192 livers (362 photographs and 7240 patches) were included. When setting a macrosteatosis threshold of 30%, the best results were obtained using the random forest classifier, achieving an AUROC = 0.74, with 85% accuracy. CONCLUSION Machine learning coupled with liver texture and color analysis of photographs taken with smartphones provides excellent accuracy for determining liver steatosis.
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Affiliation(s)
- Concepción Gómez-Gavara
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Itxarone Bilbao
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Gemma Piella
- Barcelona MedTech, Universidad Pompeu Fabra, Barcelona, Spain
| | - Javier Vazquez-Corral
- Computer Vision Center and Computer Sciences Department, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Elizabeth Pando
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - José Andrés Molino
- Servicio de Cirugía Pediátrica, Hospital Universitari Vall d´Hebron, Barcelona, Spain
| | - María Teresa Salcedo
- Servicio de Anatomía Patológica, Hospital Universitari Vall d´Hebron, Barcelona, Spain
| | - Mar Dalmau
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Laura Vidal
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Daniel Esono
- Barcelona MedTech, Universidad Pompeu Fabra, Barcelona, Spain
| | | | - Ángela Bilbao
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Josa Prats
- Barcelona MedTech, Universidad Pompeu Fabra, Barcelona, Spain
| | - Mar Moya
- Barcelona MedTech, Universidad Pompeu Fabra, Barcelona, Spain
| | - Cristina Dopazo
- Barcelona Autonoma University, Universitat Autónoma de Barcelona, Barcelona, Spain
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Christopher Mazo
- Coordinación de Trasplantes, Hospital Universitari Vall d´Hebron, Barcelona, Spain
| | - Mireia Caralt
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Ernest Hidalgo
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
| | - Ramon Charco
- Servicio de Cirugía HBP y Trasplante, Hospital Universitari Vall d´Hebron, Vall d´Hebron Institute of Research (VHIR), Barcelona, Spain
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Wehrle CJ, de Goeij FHC, Zhang M, Abbassi F, Satish S, Jiao C, Sun K, Pinna AD, Hashimoto K, Miller C, Polak WG, Clavien PA, De Jonge J, Schlegel A. Core outcome sets and benchmarking complications: Defining best practices for standardized outcome reporting in liver transplantation. Liver Transpl 2024:01445473-990000000-00469. [PMID: 39311852 DOI: 10.1097/lvt.0000000000000494] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 09/05/2024] [Indexed: 12/06/2024]
Abstract
The comparison of outcomes in liver transplantation (LT) is hampered by using clinically nonrelevant surrogate endpoints and considerable variability in reported relevant posttransplant outcomes. Such variability stems from nonstandard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is nonspecific to an intervention, and there are unsolved dilemmas specifically related to LT. Core outcome sets (COSs) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the 5 major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index. The Clavien scale and Comprehensive Complications Index are specifically reviewed to enhance their utility in LT, and their use, along with the COS, is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system and Comprehensive Complications Index to improve the reproducibility and generalizability of research concerning LT.
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Affiliation(s)
- Chase J Wehrle
- Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA
| | - Femke H C de Goeij
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Mingyi Zhang
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Fariba Abbassi
- Department of Surgery & Transplantation, University of Zurich, Zurich, Switzerland
| | | | - Chunbao Jiao
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Keyue Sun
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Antonio D Pinna
- Transplant Center, Cleveland Clinic Florida, Weston, Florida, USA
| | - Koji Hashimoto
- Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Charles Miller
- Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA
| | - Wojciech G Polak
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Pierre-Alain Clavien
- Transplant Center, Wyss Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - Jeroen De Jonge
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Andrea Schlegel
- Transplant Center, Cleveland Clinic, Cleveland, Ohio, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
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7
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Coilly A, Desterke C, Kaščáková S, Chiappini F, Samuel D, Vibert E, Guettier C, Le Naour F. Clinical Application of Infrared Spectroscopy in Liver Transplantation for Rapid Assessment of Lipid Content in Liver Graft. J Transl Med 2024; 104:102110. [PMID: 39004345 DOI: 10.1016/j.labinv.2024.102110] [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: 12/19/2023] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 07/16/2024] Open
Abstract
Liver transplantation (LT) is a major treatment for patients with end-stage liver diseases. Steatosis is a significant risk factor for primary graft nonfunction and associated with poor long-term graft outcomes. Traditionally, the evaluation of steatosis is based on frozen section examination to estimate the percentage of hepatocytes containing lipid vesicles. However, this visual evaluation correlates poorly with the true lipid content. This study aimed to address the potential of infrared (IR) microspectroscopy for rapidly estimating lipid content in the context of LT and assessing its impact on survival. Clinical data were collected for >20 months from 58 patients who underwent transplantation. For each liver graft, macrovacuolar steatosis and microvesicular steatosis were evaluated through histologic examination of frozen tissue section. Triglycerides (TG) were further quantified using gas phase chromatography coupled with a flame ionization detector (GC-FID) and estimated by IR microspectroscopy. A linear relationship and significant correlation were observed between the TG measured by GC-FID and those estimated using IR microspectroscopy (R2 = 0.86). In some cases, microvesicular steatosis was related to high lipid content despite low levels of macrovacuolar steatosis. Seven patients experienced posttransplantation liver failure, including 5 deceased patients. All patients underwent transplantation with grafts containing significantly high TG levels. A concentration of 250 nmol/mg was identified as the threshold above which the risk of failure after LT significantly increased, affecting 35% of patients. Our study established a strong correlation between LT outcomes and lipid content. IR microspectroscopy proved to be a rapid and reliable approach for assessing the lipid content in clinical settings.
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Affiliation(s)
- Audrey Coilly
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Christophe Desterke
- Université Paris Saclay, Institut André Lwoff, Villejuif, France; Inserm, US33, Villejuif, France
| | - Slávka Kaščáková
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France
| | - Franck Chiappini
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France
| | - Didier Samuel
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Eric Vibert
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France
| | - Catherine Guettier
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; AP-HP Hôpital Bicêtre, Service d'Anatomopathologie, Kremlin-Bicêtre, France.
| | - François Le Naour
- Inserm, Unité 1193, Villejuif, France; Université Paris Saclay, Institut André Lwoff, Villejuif, France; Inserm, US33, Villejuif, France.
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8
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Schurink IJ, de Goeij FHC, van der Heijden FJ, van Rooden RM, van Dijk MC, Polak WG, van der Laan LJW, Huurman VAL, de Jonge J. Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation. EPMA J 2024; 15:545-558. [PMID: 39239110 PMCID: PMC11372035 DOI: 10.1007/s13167-024-00371-7] [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: 04/04/2024] [Accepted: 06/29/2024] [Indexed: 09/07/2024]
Abstract
Purpose In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. Methods aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. Results The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301-451) µg/kg/h versus those who did not 105 (70-158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = - 0.755) and aspartate transaminase (AST; R = - 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346-453) µg/kg/h) from those who were discarded (155 (87-206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. Conclusions This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-024-00371-7.
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Affiliation(s)
- Ivo J Schurink
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
| | - Femke H C de Goeij
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
| | - Fenna J van der Heijden
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
| | - Rutger M van Rooden
- LUMC Transplant Center, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Madeleine C van Dijk
- LUMC Transplant Center, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wojciech G Polak
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
| | - Luc J W van der Laan
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
| | - Volkert A L Huurman
- LUMC Transplant Center, Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Jeroen de Jonge
- Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, Zuid Holland The Netherlands
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9
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Seth R, Andreoni KA. Changing landscape of liver transplant in the United States- time for a new innovative way to define and utilize the "non-standard liver allograft"-a proposal. FRONTIERS IN TRANSPLANTATION 2024; 3:1449407. [PMID: 39176402 PMCID: PMC11338891 DOI: 10.3389/frtra.2024.1449407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 07/22/2024] [Indexed: 08/24/2024]
Abstract
Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.
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Affiliation(s)
- Rashmi Seth
- Department of Surgery, Division of Transplant Surgery, University of Tennessee Health Sciences Center, Methodist University Hospital Transplant Institute, Memphis, TN, United States
| | - Kenneth A. Andreoni
- Department of Surgery, Division of Abdominal Transplantation, Thomas Jefferson University, Philadelphia, PA, United States
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10
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Wehrle CJ, Zhang M, Khalil M, Pita A, Modaresi Esfeh J, Diago-Uso T, Kim J, Aucejo F, Kwon DCH, Ali K, Cazzaniga B, Miyazaki Y, Liu Q, Fares S, Hong H, Tuul M, Jiao C, Sun K, Fairchild RL, Quintini C, Fujiki M, Pinna AD, Miller C, Hashimoto K, Schlegel A. Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis. Ann Surg 2024; 280:300-310. [PMID: 38557793 DOI: 10.1097/sla.0000000000006291] [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: 04/04/2024]
Abstract
OBJECTIVE Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.
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Affiliation(s)
| | | | | | | | - Jamak Modaresi Esfeh
- Department of Gastroenterology and Transplant Hepatology, Cleveland Clinic, Cleveland, OH
| | - Teresa Diago-Uso
- Department of Liver Transplantation, Cleveland Clinic Abu Dhabi, Cleveland, OH
| | - Jaekeun Kim
- Transplantation Center, Cleveland Clinic, OH
| | | | | | - Khaled Ali
- Transplantation Center, Cleveland Clinic, OH
| | | | | | - Qiang Liu
- Transplantation Center, Cleveland Clinic, OH
| | - Sami Fares
- Transplantation Center, Cleveland Clinic, OH
| | - Hanna Hong
- Transplantation Center, Cleveland Clinic, OH
| | | | - Chunbao Jiao
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH
| | - Keyue Sun
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH
| | - Robert L Fairchild
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH
| | - Cristiano Quintini
- Department of Liver Transplantation, Cleveland Clinic Abu Dhabi, Cleveland, OH
| | | | | | | | - Koji Hashimoto
- Transplantation Center, Cleveland Clinic, OH
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH
| | - Andrea Schlegel
- Transplantation Center, Cleveland Clinic, OH
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH
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11
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Wehrle CJ, Raj R, Maspero M, Satish S, Eghtesad B, Pita A, Kim J, Khalil M, Calderon E, Orabi D, Zervos B, Modaresi Esfeh J, Whitsett Linganna M, Diago-Uso T, Fujiki M, Quintini C, Kwon CD, Miller C, Pinna A, Aucejo F, Hashimoto K, Schlegel A. Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience. Int J Surg 2024; 110:2818-2831. [PMID: 38241354 PMCID: PMC11093438 DOI: 10.1097/js9.0000000000001104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 01/08/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. METHODS A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. RESULTS Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% ( n =504) and 86.6% ( n =493). Five-year RFS and OS were 78.9% ( n =449) and 79.1% ( n =450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9-0.95). Tumour size greater than 3 cm ( P =0.012), increasing tumour number on imaging ( P =0.001) and explant pathology ( P <0.001) was associated with recurrence. Transplant within Milan ( P <0.001) or UCSF criteria ( P <0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence ( P <0.001) and reduced OS ( P =0.008). Chemoembolization was predictive of recurrence in the overall population ( P =0.043) and in those outside-Milan criteria ( P =0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS ( P <0.001) in the total cohort and predict both, RFS ( P =0.007) and OS ( P =0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts ( n =15/58, 25.6%, P =0.009). Donor age was associated with a higher HCC recurrence ( P =0.006). Both total ischaemia time (TIT) greater than 6hours ( P =0.016) and increasing TIT correlated with higher HCC recurrence ( P =0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence ( P =0.039) and reduced survival ( P =0.033). CONCLUSION This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.
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Affiliation(s)
- Chase J. Wehrle
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Roma Raj
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Marianna Maspero
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Sangeeta Satish
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Bijan Eghtesad
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Alejandro Pita
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Jaekeun Kim
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Mazhar Khalil
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Esteban Calderon
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Danny Orabi
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Bobby Zervos
- Cleveland Clinic Weston Hospital, Department of Liver Transplantation, Weston, FL, USA
| | | | | | - Teresa Diago-Uso
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Masato Fujiki
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Cristiano Quintini
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Choon David Kwon
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Charles Miller
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Antonio Pinna
- Cleveland Clinic Weston Hospital, Department of Liver Transplantation, Weston, FL, USA
| | - Federico Aucejo
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Koji Hashimoto
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Andrea Schlegel
- Transplantation Center, Department of Surgery, Digestive Disease Institute
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, OH
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12
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Abbas SH, Ceresa CDL, Pollok JM. Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury. Int J Mol Sci 2024; 25:4648. [PMID: 38731866 PMCID: PMC11083584 DOI: 10.3390/ijms25094648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/21/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.
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Affiliation(s)
- Syed Hussain Abbas
- Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX1 2JD, UK;
| | - Carlo Domenico Lorenzo Ceresa
- Department of Hepatopancreatobiliary and Liver Transplant Surgery, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK;
| | - Joerg-Matthias Pollok
- Department of Hepatopancreatobiliary and Liver Transplant Surgery, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK;
- Division of Surgery & Interventional Science, University College London, Gower Street, London WC1E 6BT, UK
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13
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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14
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Akabane M, Imaoka Y, Esquivel CO, Melcher ML, Kwong A, Sasaki K. Overcoming the hurdles of steatotic grafts in liver transplantation: Insights into survival and prognostic factors. Liver Transpl 2024; 30:376-385. [PMID: 37616509 DOI: 10.1097/lvt.0000000000000245] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 08/08/2023] [Indexed: 08/26/2023]
Abstract
With increasing metabolic dysfunction-associated steatotic liver disease, the use of steatotic grafts in liver transplantation (LT) and their impact on postoperative graft survival (GS) needs further exploration. Analyzing adult LT recipient data (2002-2022) from the United Network for Organ Sharing database, outcomes of LT using steatotic (≥30% macrosteatosis) and nonsteatotic donor livers, donors after circulatory death, and standard-risk older donors (age 45-50) were compared. GS predictors were evaluated using Kaplan-Meier and Cox regression analyses. Of the 35,345 LT donors, 8.9% (3,155) were fatty livers. The initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and nonfatty livers subsided over time ( p = 0.10 at 5 y). Long-term GS outcomes showed comparable or even superior results in fatty livers relative to nonsteatotic livers, conditional on surviving the initial 90 postoperative days ( p = 0.90 at 1 y) or 1 year ( p = 0.03 at 5 y). In the multivariable Cox regression analysis, the high body surface area (BSA) ratio (≥1.1) (HR 1.42, p = 0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5 h) (HR 1.72, p < 0.01), and recipient medical condition (intensive care unit hospitalization) (HR 2.53, p < 0.01) emerged as significant adverse prognostic factors. Young (<40 y) fatty donors showed a high BSA ratio, diabetes, and intensive care unit hospitalization as significant indicators of a worse prognosis ( p < 0.01). Our study emphasizes the initial postoperative 30-day survival challenge in LT using fatty livers. However, with careful donor-recipient matching, for example, avoiding the use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the intensive care unit, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using nonfatty livers, donors after circulatory death livers, or standard-risk older donors can be anticipated. These novel insights into decision-making criteria for steatotic liver use provide invaluable guidance for clinicians.
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Affiliation(s)
- Miho Akabane
- Department of Surgery, Division of Abdominal Transplant, Stanford University Medical Center, Stanford, California, USA
| | - Yuki Imaoka
- Department of Surgery, Division of Abdominal Transplant, Stanford University Medical Center, Stanford, California, USA
| | - Carlos O Esquivel
- Department of Surgery, Division of Abdominal Transplant, Stanford University Medical Center, Stanford, California, USA
| | - Marc L Melcher
- Department of Surgery, Division of Abdominal Transplant, Stanford University Medical Center, Stanford, California, USA
| | - Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, California, USA
| | - Kazunari Sasaki
- Department of Surgery, Division of Abdominal Transplant, Stanford University Medical Center, Stanford, California, USA
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15
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Oruc M, Gedik ME, Uner M, Ulug E, Unal RN, Gunaydin G, Dogrul AB. Effectiveness of metformin for the reversal of cold-ischemia-induced damage in hepatosteatosis. Clin Res Hepatol Gastroenterol 2024; 48:102314. [PMID: 38467276 DOI: 10.1016/j.clinre.2024.102314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 02/12/2024] [Accepted: 03/06/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND Primary dysfunction and rejection are more common in donor liver tissues with steatosis. AMP-activated protein kinase (AMPK) assumes organ-protective functions during ischemia. Metformin was used for the activation of AMPK in hepatocytes. The aim of this study is to investigate the effectiveness of metformin administration for the reversal of cold-ischemia-induced damage in hepatosteatosis. MATERIAL AND METHODS Seven-week-old C7BL56 male-mice (n = 109) were separated into four groups depending on diet type and metformin use. A specific diet model was followed for 10 weeks to induce hepatosteatosis. A group of the animals was administered with metformin for the last four weeks via oral gavage. After resection, the liver tissues were perfused and kept for 0-6-12-24 h in the UW solution. Histopathological examinations were performed, and Western blot was utilized to analyze p-AMPK and AMPK expression levels. RESULTS Hepatosteatosis decreased significantly with metformin. The steatotic liver group had more prominent pericentral inflammation, necrosis as well as showing a decreased and more delayed AMPK response than the non-fat group. All these alterations could be corrected using metformin. CONCLUSION Metformin can increase the resistance of livers with hepatosteatosis to cold-ischemia-induced damage, which in turn may pave the way for successful transplantation of fatty living-donor livers.
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Affiliation(s)
- Mustafa Oruc
- Department of General Surgery, Faculty Of Medicine, School of Medicine, Hacettepe University, Floor B, 06230, Ankara, Altindag 06230, Turkey
| | - Mustafa Emre Gedik
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara 06230, Turkey
| | - Meral Uner
- Department of Pathology, Hacettepe University School of Medicine, Ankara 06230, Turkey
| | - Elif Ulug
- Department of Nutrition and Dietetics, Hacettepe University, Ankara 06230, Turkey
| | - Reyhan Nergiz Unal
- Department of Nutrition and Dietetics, Hacettepe University, Ankara 06230, Turkey
| | - Gurcan Gunaydin
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara 06230, Turkey
| | - Ahmet Bulent Dogrul
- Department of General Surgery, Faculty Of Medicine, School of Medicine, Hacettepe University, Floor B, 06230, Ankara, Altindag 06230, Turkey.
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16
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Kikuchi AT, Akanuma N, Choi WT, Gill RM, Kakar S. Assessment of large droplet fat in frozen sections of donor liver biopsies: utility and interobserver variability of the newly described Banff method compared to a simplified Average of Fields method. J Clin Pathol 2024; 77:151-156. [PMID: 38053274 DOI: 10.1136/jcp-2023-209237] [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: 10/13/2023] [Accepted: 11/09/2023] [Indexed: 12/07/2023]
Abstract
AIMS There is great variability in the assessment and reporting of fat in frozen sections of donor liver biopsies. The Banff Working Group has proposed a novel method and definition for scoring large droplet fat (LDF) in donor liver biopsies. This study compares the Banff method with a simpler Average of Fields (AF) method and evaluates the impact of different LDF definitions. METHODS Three pathologists assessed percentage of LDF (LDF%) in 10 donor liver biopsies using Banff and AF methods, applying the Banff LDF definition (cell distention with a single droplet larger than adjacent hepatocytes). Additionally, LDF% by the AF method was compared using two LDF definitions: Banff definition versus LDF definition 2 (single fat droplet occupying greater than half of a hepatocyte with nuclear displacement). RESULTS Intraobserver concordance between the Banff and AF methods was similar for all three pathologists (kappa 0.76-1). Both methods exhibited 70% interobserver concordance, and there was substantial agreement (kappa 0.68) in the LDF% among the three pathologists for both methods. Comparing the two LDF definitions, results were significantly lower with the Banff definition; LDF >50% was observed in four cases with LDF definition 2 but none of the cases with the Banff definition. CONCLUSIONS There is high interobserver and intraobserver concordance of LDF% between the Banff and AF methods. LDF% determined by the Banff definition was lower than with LDF definition 2, and needs to be validated based on graft outcome before it can be recommended for clinical use.
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Affiliation(s)
- Alexander T Kikuchi
- Pathology, University of California San Francisco, San Francisco, California, USA
- Pathology, University of Utah Health, Salt Lake City, Utah, USA
| | - Naoki Akanuma
- Pathology, University of California San Francisco, San Francisco, California, USA
| | - Won-Tak Choi
- Pathology, University of California San Francisco, San Francisco, California, USA
| | - Ryan M Gill
- Pathology, University of California San Francisco, San Francisco, California, USA
| | - Sanjay Kakar
- Pathology, University of California San Francisco, San Francisco, California, USA
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17
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Wang BK, Chen AY, Prasadh J, Desai D, Shubin AD, Raschzok N, MacConmara M, Ivanics T, Cotter T, Hwang C, Shah JA, Mufti A, Vagefi PA, Hanish SI, Patel MS. A contemporary analysis of 20,086 deceased donor liver biopsies. World J Surg 2024; 48:437-445. [PMID: 38310313 DOI: 10.1002/wjs.12034] [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: 10/08/2023] [Accepted: 11/14/2023] [Indexed: 02/05/2024]
Abstract
BACKGROUND Pre-transplant deceased donor liver biopsy may impact decision making; however, interpretation of the results remains variable and depends on accepting center practice patterns. METHODS In this cohort study, adult recipients from 04/01/2015-12/31/2020 were identified using the UNOS STARfile data. The deceased donor liver biopsies were stratified by risk based on degree of fibrosis, macrovesicular fat content, and level of portal infiltration (low-risk: no fibrosis, no portal infiltrates, and <30% macrosteatosis; moderate-risk: some fibrosis or mild infiltrates and <30% macrosteatosis; high-risk: most fibrosis, moderate/marked infiltrates, or ≥30% macrosteatosis). Graft utilization, donor risk profile, and recipient outcomes were compared across groups. RESULTS Of the 51,094 donor livers available, 20,086 (39.3%) were biopsied, and 34,606 (67.7%) were transplanted. Of the transplanted livers, 14,908 (43.1%) were biopsied. The transplanted grafts had lower mean macrovesicular fat content (9.3% transplanted vs. 26.9% non-transplanted, P < 0.001) and less often had any degree of fibrosis (20.9% vs. 39.9%, P < 0.001) or portal infiltration (51.3% vs. 58.2%, P < 0.001) versus non-transplanted grafts. Post-transplant recipient LOS (14.2 days high-risk vs. 15.2 days low-risk, P = 0.170) and 1-year graft survival (90.5% vs. 91.7%, P = 0.137) did not differ significantly between high- versus low-risk groups. Kaplan-Meier survival estimates further revealed no differences in the 5-year graft survival across risk strata (P = 0.833). Of the 5178 grafts biopsied and turned down, PSM revealed 1338 (26.0%) were potentially useable based on biopsy results and donor characteristics. CONCLUSION Carefully matched deceased donor livers with some fibrosis, inflammation, or steatosis ≥30% may be suitable for transplantation. Further study of this group of grafts may decrease turndowns of potentially useable organs.
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Affiliation(s)
- Benjamin K Wang
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Alyssa Y Chen
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jai Prasadh
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Drewv Desai
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Andrew D Shubin
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Nathanael Raschzok
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | | | - Tommy Ivanics
- Department of Surgery, Henry Ford Medical Center, Detroit, Michigan, USA
| | - Thomas Cotter
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Christine Hwang
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Jigesh A Shah
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Arjmand Mufti
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Parsia A Vagefi
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Steven I Hanish
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Madhukar S Patel
- Department of Surgery, Division of Surgical Transplantation, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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18
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Zhang X, Dutton M, Liu R, Ali AA, Sherbeny F. Deep Learning-Based Survival Analysis for Receiving a Steatotic Donor Liver Versus Waiting for a Standard Liver. Transplant Proc 2023; 55:2436-2443. [PMID: 37872066 DOI: 10.1016/j.transproceed.2023.09.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/12/2023] [Accepted: 09/22/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND An emerging strategy to expand the donor pool is the use of a steatotic donor liver (SDLs; ≥ 30% macrosteatosis on biopsy). With the obesity epidemic and prevalence of nonalcoholic fatty liver disease, SDLs have been reported in 59% of all deceased donors. Many potential candidates need to decide whether to accept an SDL offer or remain on the waitlist for a nonsteatotic donor liver (non-SDL). The objective of this study was to compare the survival of accepting an SDL vs using a non-SDL after waiting various times. METHODS Using data from the United States' organ procurement and transplantation network, deep survival learning predictive models were built to compare post-decision survival after accepting an SDL vs waiting for a non-SDL. The comparison subjects contain simulated 20,000 different scenarios of a candidate either accepting an SDL immediately or receiving a non-SDL after waiting various times. The research variables were selected using the LASSO-Cox and Random Survival Forest (RSF) models. The Cox proportional hazards and RSF models were also comparatively included for survival prediction. In addition, personalized survival curves for randomly selected candidates were generated. RESULT Deep survival learning outperformed Cox proportional hazards and RSF in predicting the survival of liver transplants. Among the simulations, 25% to 30% of scenarios demonstrated a higher 3-year survival post-decision for candidates accepting an SDL than waiting and receiving a non-SDL. The difference was only 1.43% in 3-year survival post-decision between accepting an SDL and waiting 260 days (mean waitlist time) for a non-SDL. As the number of days on the waitlist increases, the difference in survival between accepting SDLs and waiting for non-SDLs decreases. CONCLUSIONS Appropriately used SDLs could expand the donor pool and relieve the candidates' unmet need for donor livers, which presents long-term survival benefits for recipients.
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Affiliation(s)
- Xiao Zhang
- Economic, Social and Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida.
| | - Matthew Dutton
- Economic, Social and Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida
| | - Rongjie Liu
- Department of Statistics, Florida State University, Tallahassee, Florida
| | - Askal A Ali
- Economic, Social and Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida
| | - Fatimah Sherbeny
- Economic, Social and Administrative Pharmacy, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida
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19
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Patrono D, De Stefano N, Vissio E, Apostu AL, Petronio N, Vitelli G, Catalano G, Rizza G, Catalano S, Colli F, Chiusa L, Romagnoli R. How to Preserve Steatotic Liver Grafts for Transplantation. J Clin Med 2023; 12:3982. [PMID: 37373676 DOI: 10.3390/jcm12123982] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/05/2023] [Accepted: 06/08/2023] [Indexed: 06/29/2023] Open
Abstract
Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.
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Affiliation(s)
- Damiano Patrono
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Nicola De Stefano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Elena Vissio
- Department of Pathology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Ana Lavinia Apostu
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Nicoletta Petronio
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giovanni Vitelli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giorgia Catalano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Giorgia Rizza
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Silvia Catalano
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Fabio Colli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Luigi Chiusa
- Department of Pathology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Università di Torino, Corso Bramante 88-90, 10126 Turin, Italy
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20
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Schlegel A, Mergental H, Fondevila C, Porte RJ, Friend PJ, Dutkowski P. Machine perfusion of the liver and bioengineering. J Hepatol 2023; 78:1181-1198. [PMID: 37208105 DOI: 10.1016/j.jhep.2023.02.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 05/21/2023]
Abstract
With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion - one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today's perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with "repaired" autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.
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Affiliation(s)
- Andrea Schlegel
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, 20122, Italy; Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland
| | - Hynek Mergental
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, United Kingdom
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Robert J Porte
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB & Transplant Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Peter J Friend
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland.
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21
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Long JJ, Nijhar K, Jenkins RT, Yassine A, Motter JD, Jackson KR, Jerman S, Besharati S, Anders RA, Dunn TB, Marsh CL, Rayapati D, Lee DD, Barth RN, Woodside KJ, Philosophe B. Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy. Liver Transpl 2023; 29:268-278. [PMID: 36651194 DOI: 10.1097/lvt.0000000000000064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 10/06/2022] [Indexed: 01/19/2023]
Abstract
Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.
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Affiliation(s)
- Jane J Long
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kieranjeet Nijhar
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Reed T Jenkins
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Adham Yassine
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jennifer D Motter
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kyle R Jackson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Sepideh Besharati
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Robert A Anders
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ty B Dunn
- Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
| | - Christopher L Marsh
- Department of Transplant Surgery, Scripps Center of Organ Transplantation, La Jolla, California, USA
| | - Divya Rayapati
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - David D Lee
- Department of Surgery, Stritch School of Medicine, Loyola University Chicago, Chicago, Illinois, USA
| | - Rolf N Barth
- Department of Surgery, University of Maryland Medical Center, Baltimore, Maryland, USA
| | | | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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22
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Ivanics T, So D, Claasen MPAW, Wallace D, Patel MS, Gravely A, Choi WJ, Shwaartz C, Walker K, Erdman L, Sapisochin G. Machine learning-based mortality prediction models using national liver transplantation registries are feasible but have limited utility across countries. Am J Transplant 2023; 23:64-71. [PMID: 36695623 DOI: 10.1016/j.ajt.2022.12.002] [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: 06/13/2022] [Revised: 10/04/2022] [Accepted: 10/14/2022] [Indexed: 01/13/2023]
Abstract
Many countries curate national registries of liver transplant (LT) data. These registries are often used to generate predictive models; however, potential performance and transferability of these models remain unclear. We used data from 3 national registries and developed machine learning algorithm (MLA)-based models to predict 90-day post-LT mortality within and across countries. Predictive performance and external validity of each model were assessed. Prospectively collected data of adult patients (aged ≥18 years) who underwent primary LTs between January 2008 and December 2018 from the Canadian Organ Replacement Registry (Canada), National Health Service Blood and Transplantation (United Kingdom), and United Network for Organ Sharing (United States) were used to develop MLA models to predict 90-day post-LT mortality. Models were developed using each registry individually (based on variables inherent to the individual databases) and using all 3 registries combined (variables in common between the registries [harmonized]). The model performance was evaluated using area under the receiver operating characteristic (AUROC) curve. The number of patients included was as follows: Canada, n = 1214; the United Kingdom, n = 5287; and the United States, n = 59,558. The best performing MLA-based model was ridge regression across both individual registries and harmonized data sets. Model performance diminished from individualized to the harmonized registries, especially in Canada (individualized ridge: AUROC, 0.74; range, 0.73-0.74; harmonized: AUROC, 0.68; range, 0.50-0.73) and US (individualized ridge: AUROC, 0.71; range, 0.70-0.71; harmonized: AUROC, 0.66; range, 0.66-0.66) data sets. External model performance across countries was poor overall. MLA-based models yield a fair discriminatory potential when used within individual databases. However, the external validity of these models is poor when applied across countries. Standardization of registry-based variables could facilitate the added value of MLA-based models in informing decision making in future LTs.
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Affiliation(s)
- Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada; Department of Surgery, Henry Ford Hospital, Detroit, Michigan, USA; Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Delvin So
- The Centre of Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Marco P A W Claasen
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada; Department of Surgery, division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - David Wallace
- Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine and Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Annabel Gravely
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada
| | - Woo Jin Choi
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada
| | - Chaya Shwaartz
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada
| | - Kate Walker
- Department of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Lauren Erdman
- The Centre of Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network Toronto, Ontario, Canada.
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23
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Zhang X, Gavaldà R, Baixeries J. Interpretable prediction of mortality in liver transplant recipients based on machine learning. Comput Biol Med 2022; 151:106188. [PMID: 36306583 DOI: 10.1016/j.compbiomed.2022.106188] [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: 01/08/2022] [Revised: 09/24/2022] [Accepted: 10/08/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Accurate prediction of the mortality of post-liver transplantation is an important but challenging task. It relates to optimizing organ allocation and estimating the risk of possible dysfunction. Existing risk scoring models, such as the Balance of Risk (BAR) score and the Survival Outcomes Following Liver Transplantation (SOFT) score, do not predict the mortality of post-liver transplantation with sufficient accuracy. In this study, we evaluate the performance of machine learning models and establish an explainable machine learning model for predicting mortality in liver transplant recipients. METHOD The optimal feature set for the prediction of the mortality was selected by a wrapper method based on binary particle swarm optimization (BPSO). With the selected optimal feature set, seven machine learning models were applied to predict mortality over different time windows. The best-performing model was used to predict mortality through a comprehensive comparison and evaluation. An interpretable approach based on machine learning and SHapley Additive exPlanations (SHAP) is used to explicitly explain the model's decision and make new discoveries. RESULTS With regard to predictive power, our results demonstrated that the feature set selected by BPSO outperformed both the feature set in the existing risk score model (BAR score, SOFT score) and the feature set processed by principal component analysis (PCA). The best-performing model, extreme gradient boosting (XGBoost), was found to improve the Area Under a Curve (AUC) values for mortality prediction by 6.7%, 11.6%, and 17.4% at 3 months, 3 years, and 10 years, respectively, compared to the SOFT score. The main predictors of mortality and their impact were discussed for different age groups and different follow-up periods. CONCLUSIONS Our analysis demonstrates that XGBoost can be an ideal method to assess the mortality risk in liver transplantation. In combination with the SHAP approach, the proposed framework provides a more intuitive and comprehensive interpretation of the predictive model, thereby allowing the clinician to better understand the decision-making process of the model and the impact of factors associated with mortality risk in liver transplantation.
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Affiliation(s)
- Xiao Zhang
- Department of Computer Science, Universitat Politècnica de Catalunya, Barcelona, 08034, Spain.
| | | | - Jaume Baixeries
- Department of Computer Science, Universitat Politècnica de Catalunya, Barcelona, 08034, Spain
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Scalera I, De Carlis R, Patrono D, Gringeri E, Olivieri T, Pagano D, Lai Q, Rossi M, Gruttadauria S, Di Benedetto F, Cillo U, Romagnoli R, Lupo LG, De Carlis L. How useful is the machine perfusion in liver transplantation? An answer from a national survey. Front Surg 2022; 9:975150. [PMID: 36211259 PMCID: PMC9535084 DOI: 10.3389/fsurg.2022.975150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27–24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.
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Affiliation(s)
- Irene Scalera
- Hepatobiliary and Liver Transplant Unit, Department of Emergency and Organ Transplantation, University Hospital Policlinic of Bari, Bari, Italy
- Correspondence: Irene Scalera
| | - R. De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - D. Patrono
- General Surgery 2U-Liver Transplant Centre, A.O.U. “Città della Salute e della Scienza”, Turin, Italy
| | - E. Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, University Hospital of Padua, Padua, Italy
| | - T. Olivieri
- Hepato-Pancreato-Biliary Surgery and Liver Transplant Center, University of Modena and Reggio Emilia, Modena, Italy
| | - D. Pagano
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT, UPMC, Palermo, Italy
- Department of Surgery and Medical and Surgical Specialties, University of Catania, Catania, Italy
| | - Q. Lai
- Liver Transplant Unit, Sapienza University of Rome, Rome, Italy
| | - M. Rossi
- Liver Transplant Unit, Sapienza University of Rome, Rome, Italy
| | - S. Gruttadauria
- Department for the Treatment and the Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT, UPMC, Palermo, Italy
- Department of Surgery and Medical and Surgical Specialties, University of Catania, Catania, Italy
| | - F. Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplant Center, University of Modena and Reggio Emilia, Modena, Italy
| | - U. Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, University Hospital of Padua, Padua, Italy
| | - R. Romagnoli
- General Surgery 2U-Liver Transplant Centre, A.O.U. “Città della Salute e della Scienza”, Turin, Italy
| | - L. G. Lupo
- Hepatobiliary and Liver Transplant Unit, Department of Emergency and Organ Transplantation, University Hospital Policlinic of Bari, Bari, Italy
| | - L. De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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25
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Widmer J, Eden J, Carvalho MF, Dutkowski P, Schlegel A. Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain? J Clin Med 2022; 11:jcm11175218. [PMID: 36079148 PMCID: PMC9457017 DOI: 10.3390/jcm11175218] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 08/30/2022] [Indexed: 11/28/2022] Open
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques—dissimilar to SCS—mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.
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Affiliation(s)
- Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, 50139 Florence, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
- Correspondence:
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Updated S2k Clinical Practice Guideline on Non-alcoholic Fatty Liver Disease (NAFLD) issued by the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) - April 2022 - AWMF Registration No.: 021-025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e733-e801. [PMID: 36100201 DOI: 10.1055/a-1880-2388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
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27
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Roeb E, Canbay A, Bantel H, Bojunga J, de Laffolie J, Demir M, Denzer UW, Geier A, Hofmann WP, Hudert C, Karlas T, Krawczyk M, Longerich T, Luedde T, Roden M, Schattenberg J, Sterneck M, Tannapfel A, Lorenz P, Tacke F. Aktualisierte S2k-Leitlinie nicht-alkoholische Fettlebererkrankung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – April 2022 – AWMF-Registernummer: 021–025. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:1346-1421. [PMID: 36100202 DOI: 10.1055/a-1880-2283] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Roeb
- Gastroenterologie, Medizinische Klinik II, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - A Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - H Bantel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - J Bojunga
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin., Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - J de Laffolie
- Allgemeinpädiatrie und Neonatologie, Zentrum für Kinderheilkunde und Jugendmedizin, Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
| | - M Demir
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
| | - U W Denzer
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Marburg, Deutschland
| | - A Geier
- Medizinische Klinik und Poliklinik II, Schwerpunkt Hepatologie, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz - Medizinisches Versorgungszentrum, Berlin, Deutschland
| | - C Hudert
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - T Karlas
- Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie, Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - M Krawczyk
- Klinik für Innere Medizin II, Gastroent., Hepat., Endokrin., Diabet., Ern.med., Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - T Longerich
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Luedde
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - M Roden
- Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - J Schattenberg
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland
| | - M Sterneck
- Klinik für Hepatobiliäre Chirurgie und Transplantationschirurgie, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - A Tannapfel
- Institut für Pathologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - P Lorenz
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - F Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum und Campus Charité Mitte, Berlin, Deutschland
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Philosophe B, Noel Wesson R. High time for common ground in the assessment of steatosis. Liver Transpl 2022; 28:1427-1428. [PMID: 35596619 DOI: 10.1002/lt.26506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 05/13/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Benjamin Philosophe
- Division of Transplant Surgery, Department of Surgery, The Johns Hopkins University, Baltimore, Maryland, USA
| | - Russell Noel Wesson
- Division of Transplant Surgery, Department of Surgery, The Johns Hopkins University, Baltimore, Maryland, USA.,Division of Transplant Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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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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A Novel Digital Algorithm for Identifying Liver Steatosis Using Smartphone-Captured Images. Transplant Direct 2022; 8:e1361. [PMID: 35935028 PMCID: PMC9355111 DOI: 10.1097/txd.0000000000001361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/27/2022] [Indexed: 11/26/2022] Open
Abstract
Access to lifesaving liver transplantation is limited by a severe organ shortage. One factor contributing to the shortage is the high rate of discard in livers with histologic steatosis. Livers with <30% macrosteatosis are generally considered safe for transplant. However, histologic assessment of steatosis by a pathologist remains subjective and is often limited by image quality. Here, we address this bottleneck by creating an automated digital algorithm for calculating histologic steatosis using only images of liver biopsy histology obtained with a smartphone.
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Riediger C, Schweipert J, Weitz J. Prädiktoren für erfolgreiche Lebertransplantationen und Risikofaktoren. Zentralbl Chir 2022; 147:369-380. [DOI: 10.1055/a-1866-4197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ZusammenfassungDie Lebertransplantation ist die einzige kurative Therapieoption einer chronischen Leberinsuffizienz im Endstadium. Daneben stellen onkologische Lebererkrankungen wie das HCC eine weitere
Indikation für die Lebertransplantation dar, ebenso wie das akute Leberversagen.Seit der ersten erfolgreichen Lebertransplantation durch Professor Thomas E. Starzl im Jahr 1967 haben sich nicht nur die chirurgischen, immunologischen und anästhesiologischen Techniken
und Möglichkeiten geändert, sondern auch die Indikationen und das Patientengut. Hinzu kommt, dass die Empfänger ein zunehmendes Lebensalter und damit einhergehend mehr Begleiterkrankungen
aufweisen.Die Zahl an Lebertransplantationen ist weltweit weiter ansteigend. Es benötigen aber mehr Menschen eine Lebertransplantation, als Organe zur Verfügung stehen. Dies liegt am zunehmenden
Bedarf an Spenderorganen bei gleichzeitig weiter rückläufiger Zahl postmortaler Organspenden.Diese Diskrepanz zwischen Spenderorganen und Empfängern kann nur zu einem kleinen Teil durch Split-Lebertransplantationen oder die Leberlebendspende kompensiert werden.Um den Spenderpool zu erweitern, werden zunehmend auch marginale Organe, die nur die erweiterten Spenderkriterien („extended donor criteria [EDC]“) erfüllen, allokiert. In manchen Ländern
zählen hierzu auch die sogenannten DCD-Organe (DCD: „donation after cardiac death“), d. h. Organe, die erst nach dem kardiozirkulatorischen Tod des Spenders entnommen werden.Es ist bekannt, dass marginale Spenderorgane mit einem erhöhten Risiko für ein schlechteres Transplantat- und Patientenüberleben nach Lebertransplantation einhergehen.Um die Qualität marginaler Spenderorgane zu verbessern, hat sich eine rasante Entwicklung der Techniken der Organkonservierung über die letzten Jahre gezeigt. Mit der maschinellen
Organperfusion besteht beispielsweise die Möglichkeit, die Organqualität deutlich zu verbessern. Insgesamt haben sich die Risikokonstellationen von Spenderorgan und Transplantatempfänger
deutlich geändert.Aus diesem Grunde ist es von großer Bedeutung, spezifische Prädiktoren für eine erfolgreiche Lebertransplantation sowie die entsprechenden Risikofaktoren für einen schlechten postoperativen
Verlauf zu kennen, um das bestmögliche Transplantat- und Patientenüberleben nach Lebertransplantation zu ermöglichen.Diese Einflussfaktoren, inklusive möglicher Risiko-Scores, sollen hier ebenso wie die neuen technischen Möglichkeiten in der Lebertransplantation beleuchtet werden.
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Affiliation(s)
- Carina Riediger
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Technische Universität Dresden, Dresden, Deutschland
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Deutschland
| | - Johannes Schweipert
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Technische Universität Dresden, Dresden, Deutschland
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Deutschland
| | - Jürgen Weitz
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Technische Universität Dresden, Dresden, Deutschland
- Klinik und Poliklinik für Viszeral-, Thorax-, und Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden, Deutschland
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Da BL, Satiya J, Heda RP, Jiang Y, Lau LF, Fahmy A, Winnick A, Roth N, Grodstein E, Thuluvath PJ, Singal AK, Schiano TD, Teperman LW, Satapathy SK. Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts. Euroasian J Hepatogastroenterol 2022; 12:S5-S14. [PMID: 36466105 PMCID: PMC9681573 DOI: 10.5005/jp-journals-10018-1361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2024] Open
Abstract
BACKGROUND Graft macrosteatosis can predispose to a higher risk of graft loss so we sought to redefine acceptable cutoffs for graft steatosis. METHODS Data of 26,103 donors who underwent liver transplantation (LT) between January 2004 and December 2018 from the UNOS-STAR database were utilized. A high-risk steatotic (HRS) graft and a low-risk steatotic (LRS) graft were defined as ≥20% and <20% macrosteatosis, respectively. High-risk steatotic grafts were further classified as grafts with 20-29% (G1S grafts), 30-39% (G2S grafts), and ≥40% steatosis (G3S grafts). Outcomes between groups were compared. RESULTS LRS grafts had excellent graft (93.3 and 87.7%) and overall survival (95.4 and 90.5%) at 90 days and 1 year. Compared to LRS grafts, G1S, G2S, and G3S grafts had worse graft and overall survival at 90 days and 1-year (p <0.001). There was no difference in graft or overall survival of G1S or G3S grafts compared to G2S grafts until after adjustment in which G3S grafts were found to be associated with an increased risk of graft loss-aHR 1.27 (1.03-1.57), p = 0.02. DISCUSSION Liver grafts can be categorized into three categories: (1) <20% or "very low risk", (2) 20-39% or "low-to-moderate risk", and usually acceptable, and (3) ≥40% steatosis or "moderate-to-high risk". HOW TO CITE THIS ARTICLE Da BL, Satiya J, Heda RP, et al. Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S5-S14.
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Affiliation(s)
- Ben L Da
- Division of Hepatology, Department of Internal Medicine, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Barbara and Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, United States of America
| | - Jinendra Satiya
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America
| | - Rajiv P Heda
- Department of Internal Medicine, Tulane University, New Orleans, Louisiana, United States of America
| | - Yu Jiang
- School of Public Health, University of Memphis, Memphis, Tennessee, United States of America
| | - Lawrence F Lau
- Division of Transplant, Northwell Health System Transplant Center, Northshore University Hospital, Northwell Health, Manhasset, New York, United States of America
| | - Ahmed Fahmy
- Division of Transplant, Northwell Health System Transplant Center, Northshore University Hospital, Northwell Health, Manhasset, New York, United States of America
| | - Aaron Winnick
- Division of Transplant, Northwell Health System Transplant Center, Northshore University Hospital, Northwell Health, Manhasset, New York, United States of America
| | - Nitzan Roth
- Division of Hepatology, Department of Internal Medicine, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Barbara and Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, United States of America
| | - Elliot Grodstein
- Division of Transplant, Northwell Health System Transplant Center, Northshore University Hospital, Northwell Health, Manhasset, New York, United States of America
| | - Paul J Thuluvath
- Institute of Digestive Health and Liver Disease, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Avera McKenna University Health Center and Transplant Institute, Sioux Falls, South Dakota, United States of America
| | - Thomas D Schiano
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, United States of America
| | - Lewis W Teperman
- Division of Transplant, Northwell Health System Transplant Center, Northshore University Hospital, Northwell Health, Manhasset, New York, United States of America
| | - Sanjaya K Satapathy
- Division of Hepatology, Department of Internal Medicine, Sandra Atlas Bass Center for Liver Diseases and Transplantation, Barbara and Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, United States of America
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33
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Zhao X, He Y, Liu J, Zhang Q, Liu L, Qu W, Liu Y, Zeng Z, Zhang H, Jia J, Sun L, Wei L, Zhu Z. Impact of living donor liver with steatosis and idiopathic portal inflammation on clinical outcomes in pediatric liver transplantation: Beijing experience. Hepatobiliary Surg Nutr 2022; 11:340-354. [PMID: 35693402 PMCID: PMC9186188 DOI: 10.21037/hbsn-20-685] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 12/24/2020] [Indexed: 01/24/2025]
Abstract
BACKGROUND To evaluate the impact of steatosis and/or idiopathic portal inflammation (IPI) in living donor livers on recipients' clinical outcomes. METHODS We assessed 305 qualified donor liver samples from June 2013 to December 2018. Donors and recipients' clinical characteristics, including follow-up data were retrieved. The graft and overall survival with/without steatosis or portal inflammation were compared by Kaplan-Meier analysis. RESULTS For living donors, the medium age of was 31.2 (28, 35.8) years old; liver histopathology showed macrovesicular steatosis: 0-5% 264/305 (86.6%) and 5-30% 41/305 (13.4%), IPI: no 220/305 (72.1%) and mild 85/305 (27.9%). For recipients, the medium age was 1.0 (0.6, 1.5) years old; the median pediatric-end-stage-liver-disease score was 16 (5.0, 26.0) and medium follow-up time was 32.8 (24.8, 52.0) months. Biliary atresia (69.5%) was the main indication for liver transplantation (LT). CONCLUSIONS The presence of steatosis and portal inflammation of the donor liver did not impact the clinical outcomes including transaminase or bilirubin normalization, short-/long-term complications and recipients' survival. However, recipients with high pediatric-end-stage-liver-disease score (>16) receiving donor liver with portal inflammation, but not steatosis, had trend negative effect on recipients' survival. In conclusion, donor livers with mild steatosis and portal inflammation were qualified for pediatric living donor LT. However, donor liver with mild portal inflammation would better not be allocated to recipients with high pediatric-end-stage-liver-disease score. This study provided new evidence in pediatric living donor liver allocation.
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Affiliation(s)
- Xinyan Zhao
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Yafei He
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Jimin Liu
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Qian Zhang
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- Clinical Epidemiology and Evidence Base Medicine Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Liwei Liu
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Wei Qu
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Ying Liu
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Zhigui Zeng
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Haiming Zhang
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Liying Sun
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Lin Wei
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
| | - Zhijun Zhu
- Liver Transplant Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing, China
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34
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Mergental H, Laing RW, Hodson J, Boteon YL, Attard JA, Walace LL, Neil DAH, Barton D, Schlegel A, Muiesan P, Abradelo M, Isaac JR, Roberts K, Perera MTPR, Afford SC, Mirza DF. Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High-Risk Donor Livers. Liver Transpl 2022; 28:794-806. [PMID: 34619014 DOI: 10.1002/lt.26326] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 08/23/2021] [Accepted: 09/10/2021] [Indexed: 12/14/2022]
Abstract
Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.
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Affiliation(s)
- Hynek Mergental
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Richard W Laing
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - James Hodson
- Department of Statistics, Institute for Translational Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Yuri L Boteon
- National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Joseph A Attard
- National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Laine L Walace
- National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Desley A H Neil
- Department of Cellular Pathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Darren Barton
- D3B Team, Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom
| | - Andrea Schlegel
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Paolo Muiesan
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Manuel Abradelo
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - John R Isaac
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Keith Roberts
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - M Thamara P R Perera
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Simon C Afford
- National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Darius F Mirza
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.,Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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35
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Altshuler PJ, Dang H, Frank AM, Shah AP, Glorioso J, Zhan T, Rios Diaz A, Shaheen O, Ramirez CB, Maley WR, Bodzin AS. Evaluating Outcomes Related to Donor and Recipient Metabolic Environment: Macrosteatotic Allografts and Nonalcoholic Steatohepatitis. Liver Transpl 2022; 28:623-635. [PMID: 34564931 PMCID: PMC10152802 DOI: 10.1002/lt.26313] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/19/2022]
Abstract
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%-29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score-matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long-term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high-risk macrosteatotic allografts to negatively affect outcomes.
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Affiliation(s)
- Peter J Altshuler
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Hien Dang
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Adam M Frank
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Ashesh P Shah
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Jaime Glorioso
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Tingting Zhan
- Division of Biostatistics, Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA
| | - Arturo Rios Diaz
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Osama Shaheen
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Carlo B Ramirez
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Warren R Maley
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
| | - Adam S Bodzin
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA
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36
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Yang M, Khan AR, Lu D, Wei X, Shu W, Xu C, Pan B, Zhou Z, Wang R, Wei Q, Cen B, Cai J, Zheng S, Xu X. Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation. Front Med (Lausanne) 2022; 9:772048. [PMID: 35308496 PMCID: PMC8927074 DOI: 10.3389/fmed.2022.772048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/26/2022] [Indexed: 11/24/2022] Open
Abstract
Background A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes. Method Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured. Results After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 μmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%. Conclusion The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.
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Affiliation(s)
- Mengfan Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Di Lu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Wenzhi Shu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Chuanshen Xu
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Binhua Pan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
| | - Rui Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Beini Cen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Jinzhen Cai
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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37
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Machine perfusion of the liver: applications in transplantation and beyond. Nat Rev Gastroenterol Hepatol 2022; 19:199-209. [PMID: 34997204 DOI: 10.1038/s41575-021-00557-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/17/2021] [Indexed: 12/14/2022]
Abstract
The shortage of donor livers considered suitable for transplantation has driven the development of novel methods for organ preservation and reconditioning. Machine perfusion techniques can improve the quality of marginal livers, extend the time for which they can be preserved and enable an objective assessment of their quality and viability. These benefits can help avoid the needless wastage of organs based on hypothetical concerns regarding quality. As machine perfusion techniques are gaining traction in clinical practice, attention has now shifted to their potential applications beyond transplantation. As well as providing an update on the current status of machine perfusion in clinical practice, this Perspective discusses how this technology is being used as a tool for therapeutic interventions including defatting of steatotic livers, immunomodulation and gene therapies.
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38
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BAR Score Performance in Predicting Survival after Living Donor Liver Transplantation: A Single-Center Retrospective Study. Can J Gastroenterol Hepatol 2022; 2022:2877859. [PMID: 35223683 PMCID: PMC8881181 DOI: 10.1155/2022/2877859] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/18/2022] [Accepted: 01/28/2022] [Indexed: 12/07/2022] Open
Abstract
METHODS 146 adult liver transplant recipients were included. Univariate and multivariate analyses were used to determine the independent predictors of survival at 3 months, 1 year, and 5 years. The receiver operating characteristic (ROC) curve for the BAR score was plotted, and the area under the ROC curve (AUROC) was calculated. Kaplan-Meier curve and log-rank test were used to compare survival above and below the best cutoff values. RESULTS The mean age was 52.45 ± 8.54 years, and 59.6% were males. The survival rates were 89, 78.8, and 72% at 3 months, 1 year, and 5 years, respectively. The BAR score demonstrated a clinically significant value in the prediction of 3-month (AUROC = 0.89), 1-year (AUROC = 0.76), and 5-year survival (AUROC = 0.71). Among the investigated factors associated with survival, BAR score <10 points was the only independent predictor of 3-month (OR 7.34, p < 0.0001), 1-year (OR 3.37, p=0.001), and 5-year survival (OR 2.83, p=0.044). CONCLUSIONS BAR is a simple and easily applicable scoring system that could significantly predict short- and long-term survival after LDLT. A large multicenter study is warranted to validate our results in the Egyptian population.
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39
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Schlegel A, van Reeven M, Croome K, Parente A, Dolcet A, Widmer J, Meurisse N, De Carlis R, Hessheimer A, Jochmans I, Mueller M, van Leeuwen OB, Nair A, Tomiyama K, Sherif A, Elsharif M, Kron P, van der Helm D, Borja-Cacho D, Bohorquez H, Germanova D, Dondossola D, Olivieri T, Camagni S, Gorgen A, Patrono D, Cescon M, Croome S, Panconesi R, Carvalho MF, Ravaioli M, Caicedo JC, Loss G, Lucidi V, Sapisochin G, Romagnoli R, Jassem W, Colledan M, De Carlis L, Rossi G, Di Benedetto F, Miller CM, van Hoek B, Attia M, Lodge P, Hernandez-Alejandro R, Detry O, Quintini C, Oniscu GC, Fondevila C, Malagó M, Pirenne J, IJzermans JNM, Porte RJ, Dutkowski P, Taner CB, Heaton N, Clavien PA, Polak WG, Muiesan P. A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation. J Hepatol 2022; 76:371-382. [PMID: 34655663 DOI: 10.1016/j.jhep.2021.10.004] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 09/17/2021] [Accepted: 10/04/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, United Kingdom; Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy
| | - Marjolein van Reeven
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of Hepato-Pancreato-Biliary and Transplant Surgery, Rotterdam, the Netherlands
| | - Kristopher Croome
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Alessandro Parente
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, United Kingdom
| | - Annalisa Dolcet
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; HPB Surgery and Liver Transplantation, Royal Free Hospital London, United Kingdom
| | - Nicolas Meurisse
- Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Amelia Hessheimer
- General & Digestive Surgery, Hospital Clínic Barcelona, Barcelona, Spain; CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ina Jochmans
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium; Abdominal Transplant Surgery, Department of Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Matteo Mueller
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Otto B van Leeuwen
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Amit Nair
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA; Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, NY, USA
| | - Koji Tomiyama
- Division of Transplantation/Hepatobiliary Surgery, Department of Surgery, University of Rochester, NY, USA
| | - Ahmed Sherif
- Department of Transplant Surgery, Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, United Kingdom
| | - Mohamed Elsharif
- HPB and Transplant Unit, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Philipp Kron
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; HPB and Transplant Unit, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Danny van der Helm
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Daniel Borja-Cacho
- Division of Transplantation, Department of Surgery, Northwestern Medicine, Chicago, Illinois, USA
| | - Humberto Bohorquez
- Multi-Organ Transplant Institute, University of Queensland School and the Ochsner Clinical School, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
| | - Desislava Germanova
- Department of abdominal surgery, Unit of hepato-biliary surgery and abdominal transplantation, CUB Erasme Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | - Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan 20122, Italy
| | - Tiziana Olivieri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefania Camagni
- Department of Organ Failure and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Andre Gorgen
- Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | - Damiano Patrono
- General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Sarah Croome
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Rebecca Panconesi
- Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | | | - Matteo Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Juan Carlos Caicedo
- Division of Transplantation, Department of Surgery, Northwestern Medicine, Chicago, Illinois, USA
| | - George Loss
- Multi-Organ Transplant Institute, University of Queensland School and the Ochsner Clinical School, Ochsner Clinic Foundation, New Orleans, Louisiana, USA
| | - Valerio Lucidi
- Department of abdominal surgery, Unit of hepato-biliary surgery and abdominal transplantation, CUB Erasme Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | | | - Renato Romagnoli
- General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Wayel Jassem
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Michele Colledan
- Department of Organ Failure and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy; Università di Milano-Bicocca, Milano, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Giorgio Rossi
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan 20122, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Charles M Miller
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Magdy Attia
- HPB and Transplant Unit, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Peter Lodge
- HPB and Transplant Unit, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | | | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
| | - Cristiano Quintini
- Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Gabriel C Oniscu
- Department of Transplant Surgery, Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, United Kingdom
| | - Constantino Fondevila
- General & Digestive Surgery, Hospital Clínic Barcelona, Barcelona, Spain; CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Massimo Malagó
- HPB Surgery and Liver Transplantation, Royal Free Hospital London, United Kingdom
| | - Jacques Pirenne
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium; Abdominal Transplant Surgery, Department of Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Jan N M IJzermans
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of Hepato-Pancreato-Biliary and Transplant Surgery, Rotterdam, the Netherlands
| | - Robert J Porte
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Wojciech G Polak
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of Hepato-Pancreato-Biliary and Transplant Surgery, Rotterdam, the Netherlands
| | - Paolo Muiesan
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, United Kingdom; Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan 20122, Italy.
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A Clinical Tool to Guide Selection and Utilization of Marginal Donor Livers With Graft Steatosis in Liver Transplantation. Transplant Direct 2022; 8:e1280. [PMID: 35047662 PMCID: PMC8759620 DOI: 10.1097/txd.0000000000001280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 11/03/2021] [Accepted: 11/19/2021] [Indexed: 11/26/2022] Open
Abstract
Supplemental Digital Content is available in the text. Background. Donor liver biopsy (DLBx) in liver transplantation provides information on allograft quality; however, predicting outcomes from these allografts remains difficult. Methods. Between 2006 and 2015, 16 691 transplants with DLBx were identified from the Standard Transplant Analysis and Research database. Cox proportional hazard regression analyses identified donor and recipient characteristics associated with 30-d, 90-d, 1-y, and 3-y graft survival. A composite model, the Liver Transplant After Biopsy (LTAB) score, was created. The Mini-LTAB was then derived consisting of only donor age, macrosteatosis on DLBx, recipient model for end-stage liver disease score, and cold ischemic time. Risk groups were identified for each score and graft survival was evaluated. P values <0.05 were considered significant. Results. The LTAB model used 14 variables and 5 risk groups and identified low-, mild-, moderate-, high-, and severe-risk groups. Compared with moderate-risk recipients, severe-risk recipients had increased risk of graft loss at 30 d (hazard ratio, 3.270; 95% confidence interval, 2.568-4.120) and at 1 y (2.258; 1.928-2.544). The Mini-LTAB model identified low-, moderate-, and high-risk groups. Graft survival in Mini-LTAB high-risk transplants was significantly lower than moderate- or low-risk transplants at all time points. Conclusions. The LTAB and Mini-LTAB scores represent guiding principles and provide clinically useful tools for the successful selection and utilization of marginal allografts in liver transplantation.
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Abstract
Severe allograft dysfunction, as opposed to the expected immediate function, following liver transplantation is a major complication, and the clinical manifestations of such that lead to either immediate retransplant or death are the catastrophic end of the spectrum. Primary nonfunction (PNF) has declined in incidence over the years, yet the impact on patient and healthcare teams, and the burden on the organ pool in case of the need for retransplant should not be underestimated. There is no universal test to define the diagnosis of PNF, and current criteria are based on various biochemical parameters surrogate of liver function; moreover, a disparity remains within different healthcare systems on selecting candidates eligible for urgent retransplantation. The impact on PNF from traditionally accepted risk factors has changed somewhat, mainly driven by the rising demand for organs, combined with the concerted approach by clinicians on the in-depth understanding of PNF, optimal graft recipient selection, mitigation of the clinical environment in which a marginal graft is reperfused, and postoperative management. Regardless of the mode, available data suggest machine perfusion strategies help reduce the incidence further but do not completely avert the risk of PNF. The mainstay of management relies on identifying severe allograft dysfunction at a very early stage and aggressive management, while excluding other identifiable causes that mimic severe organ dysfunction. This approach may help salvage some grafts by preventing total graft failure and also maintaining a patient in an optimal physiological state if retransplantation is considered the ultimate patient salvage strategy.
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Affiliation(s)
- Hermien Hartog
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
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de Boer JD, Putter H, Blok JJ, Cambridge NA, van den Berg SD, Vogelaar S, Berlakovich G, Guba M, Braat AE, Advisory Committee ELIAC. Development of the Eurotransplant Discard Risk Index to Predict Acceptance of Livers for Transplantation: A Retrospective Database Analysis. EXP CLIN TRANSPLANT 2021; 19:1163-1172. [PMID: 34812707 DOI: 10.6002/ect.2021.0228] [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 The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant. MATERIALS AND METHODS Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index. RESULTS Of 11670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyltranspeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P < .001), respectively. Despite strong calibration, discard rates of 0.8% for overall donors and 6% of donors after circulatory death could be predicted with 80% accuracy. CONCLUSIONS The Eurotransplant-developed Discard Risk Index showed a high prognostic ability to predict liver utilization in a European setting. The model could therefore be valuable for identifying livers at high risk of not being transplanted in an early stage. These organs might profit the most from modified allocation strategies or advanced preservation techniques.
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Affiliation(s)
- Jacob D de Boer
- From the Medical Staff Office, Eurotransplant International Foundation, Leiden, The Netherlands.,From the Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden, The Netherlands
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Barbier L, Robin A, Sindayigaya R, Ducousso H, Dujardin F, Thierry A, Hauet T, Girard JP, Pellerin L, Gombert JM, Herbelin A, Salamé E. Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation. Front Immunol 2021; 12:744927. [PMID: 34621275 PMCID: PMC8491545 DOI: 10.3389/fimmu.2021.744927] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/30/2021] [Indexed: 12/29/2022] Open
Abstract
Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33–deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.
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Affiliation(s)
- Louise Barbier
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, Tours, France.,University of Tours, Tours, France
| | - Aurélie Robin
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University Hospital of Poitiers, Poitiers, France
| | - Rémy Sindayigaya
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, Tours, France.,University of Tours, Tours, France
| | - Héloïse Ducousso
- INSERM U1082, Poitiers, France.,University Hospital of Poitiers, Poitiers, France.,University of Poitiers, Poitiers, France.,Department of Urology, University Hospital of Poitiers, Poitiers, France
| | - Fanny Dujardin
- Department of Pathology, University Hospital of Tours, Tours, France
| | - Antoine Thierry
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University Hospital of Poitiers, Poitiers, France.,University of Poitiers, Poitiers, France.,Department of Nephrology, University Hospital of Poitiers, Poitiers, France
| | - Thierry Hauet
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University Hospital of Poitiers, Poitiers, France.,University of Poitiers, Poitiers, France.,Department of Biochemistry, Pôle BIOSPHARM, University Hospital of Poitiers, Poitiers, France
| | - Jean-Philippe Girard
- Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France
| | - Luc Pellerin
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University of Poitiers, Poitiers, France
| | - Jean-Marc Gombert
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University Hospital of Poitiers, Poitiers, France.,University of Poitiers, Poitiers, France.,Department of Immunology, University Hospital of Poitiers, Poitiers, France
| | - André Herbelin
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,University of Poitiers, Poitiers, France
| | - Ephrem Salamé
- INSERM U1082, Poitiers, France.,FHU SUPORT, Tours-Poitiers-Limoges, France.,Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, Tours, France.,University of Tours, Tours, France
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Tien C, Remulla D, Kwon Y, Emamaullee J. Contemporary strategies to assess and manage liver donor steatosis: a review. Curr Opin Organ Transplant 2021; 26:474-481. [PMID: 34524179 PMCID: PMC8447219 DOI: 10.1097/mot.0000000000000893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Due to a persistent shortage of donor livers, attention has turned toward ways of utilizing marginal grafts, particularly those with steatosis, without incurring inferior outcomes. Here we review the evaluation and utilization of steatotic liver allografts, highlight recently published data, and discuss novel methods of graft rehabilitation. RECENT FINDINGS Although severe liver allograft (>60%) steatosis has been associated with inferior graft and recipient outcomes, mild (<30%) steatosis has not. There is ongoing debate regarding safe utilization of grafts with moderate (30-60%) steatosis. Presently, no established protocols for evaluating steatosis in donor candidates or utilizing such grafts exist. Liver biopsy is accepted as the gold standard technique, though noninvasive methods have shown promise in accurately predicting steatosis. More recently, machine perfusion has been shown to enhance ex situ liver function and reduce steatosis, emerging as a potential means of optimizing steatotic grafts prior to transplantation. SUMMARY Steatotic liver allografts constitute a large proportion of deceased donor organs. Further work is necessary to define safe upper limits for the acceptable degree of steatosis, develop standardized evaluation protocols, and establish utilization guidelines that prioritize safety. Machine perfusion has shown promise in rehabilitating steatotic grafts and offers the possibility of expanding the deceased donor pool.
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Affiliation(s)
- Christine Tien
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Daphne Remulla
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Yong Kwon
- Keck School of Medicine, University of Southern California, Los Angeles, CA
- Department of Surgery, University of Southern California, Los Angeles, CA
| | - Juliet Emamaullee
- Keck School of Medicine, University of Southern California, Los Angeles, CA
- Department of Surgery, University of Southern California, Los Angeles, CA
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Incarbone N, De Carlis R, Centonze L, Palmieri L, Cordaro G, Ficarelli A, Vella I, Buscemi V, Lauterio A, De Carlis L. Usefulness of T-Tube in Liver Transplantation: Still Effective or Outmoded Strategy? TRANSPLANTOLOGY 2021; 2:379-386. [DOI: 10.3390/transplantology2040036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2023] Open
Abstract
Introduction: T-tube placement during liver transplantation (LT) is still debated. We performed a retrospective study to evaluate the usefulness of T-tube after LT in two cohorts differing in post-transplant risk. Methods: A total of 327 LTs performed between 2015 and 2018 were included in the analysis. LTs from donation after circulatory death and living donation, split-liver transplants, and LTs with hepaticojejunostomy were excluded. T-tube was reserved for marginal grafts, high-risk recipients, and bile duct size discrepancy. A balance of risk (BAR) score of ≤9 defined the low-risk cohort (232 patients, 68 with and 164 without T-tube), while a BAR score of >9 defined the high-risk cohort (95 patients, 43 with and 52 without T-tube). Postoperative complications were estimated with the comprehensive complication index (CCI). Postoperative biliary complications were classified in anastomotic stricture (AS), non-anastomotic stricture (NAS), and biliary leakage (BL). Results: In the low-risk cohort, LTs with and without T-tube had similar rates of NAS (0 vs. 2.9%, p = 0.36), AS (2.9 vs. 2.4%, p = 0.83), and BL (1.4 vs. 2.4%, p = 0.64). Analogous outcomes were found in the high-risk cohort: NAS (0 vs. 0), AS (0 vs. 5.7%, p = 0.11), and BL (0 vs. 1.3%, p = 0.27). There were more postoperative complications among patients with T-tube, in both the low-risk (CCI 29 vs. 21, p < 0.001) and high-risk (CCI 51 vs. 29, p < 0.001) cohort. No differences in primary non-function, hepatic artery thrombosis, and mortality were observed. Conclusions: T-tube placement did not influence postoperative biliary complications. Although the two cohorts were normalized for post-transplant risk, LT recipients with T-tube had a more complicated course.
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Lin F, Zhen F, Yan X, Shaojun Y, Guizhu P, Yanfeng W, Qifa Y. Hypothermic oxygenated perfusion with defatting cocktail further improves steatotic liver grafts in a transplantation rat model. Artif Organs 2021; 45:E304-E316. [PMID: 33908066 DOI: 10.1111/aor.13976] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/06/2021] [Accepted: 03/19/2021] [Indexed: 12/18/2022]
Abstract
In this study, we evaluated the restoring and defatting effect of hypothermic oxygenated perfusion (HOPE) on severe steatotic liver grafts with a defatting cocktail (DF) in a rat model. Severe (≥60%) hepatic macrosteatosis was induced by a high-fat diet (HFD) for 6 weeks, after which the rats were randomly divided into four following groups: Control group, with lean livers being preserved in static cold storage (SCS) at 0°C-4°C for 45 minutes; SCS group, with a steatotic liver graft (SLG) being preserved in SCS at 0°C-4°C for 4 hours; HOPE group, where SLG was perfused with 3-hours HOPE followed by 1-hours SCS; and HOPE + DF group, HOPE with the addition of DF. Graft function after orthotopic liver transplantation was assessed in terms of mitochondrial function (adenosine triphosphate [ATP], Glycogen), endoplasmic reticulum stress (PPY, GRP78, CHOP, and ATF-6), cell apoptosis (Tunel assay, Caspase-3), inflammatory level (HMGB1, TLR4, IL-1β, IL-6. TNF-α, Factor V), and posttransplantation survival. HOPE protected steatotic liver grafts from microcirculation disturbance and endoplasmic reticulum stress and then promoted ATP and glycogen synthesis that improved mitochondrial function. Meanwhile, under conditions of ischemia-reperfusion injury, it prevented nuclear injury and endothelial damage by suppressing the release of an inflammatory mediator. The high efficacy of HOPE was enhanced after the addition of the DF. DF agents cannot promote the lipid decomposition of the steatotic liver graft at 0°C-4°C, but they can further improve steatotic liver and postoperative survival compared to the HOPE. The defatted steatotic liver grafts can be safely used in rat orthotopic liver transplantation.
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Affiliation(s)
- Fan Lin
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Fu Zhen
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Xiong Yan
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Ye Shaojun
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Peng Guizhu
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Wang Yanfeng
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Ye Qifa
- Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, PR China
- Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, PR China
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Schlegel A, Foley DP, Savier E, Flores Carvalho M, De Carlis L, Heaton N, Taner CB. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation. Transplantation 2021; 105:1892-1903. [PMID: 34416750 DOI: 10.1097/tp.0000000000003825] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - David P Foley
- University of Wisconsin School of Medicine and Public Health, William S. Middleton VA Medical Center, Madison, WI
| | - Eric Savier
- Department of Hepatobiliary Surgery and Liver Transplantation, Sorbonne Université Pitié-Salpêtrière Hospital, Paris, France
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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Zamora-Valdés D, Leal-Leyte P, Arvizu-Tachiquin PC, Cárdenas-Rodríguez RF, Ávila-Armendáriz JA, Luévano-González A. Use of liver grafts from cadaveric donors: Implementation impact of a local evaluation and procurement team in Mexico. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021; 86:220-228. [PMID: 34172431 DOI: 10.1016/j.rgmxen.2021.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 05/13/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION AND AIMS Cadaveric donor liver graft retrieval is complex in Mexico. The aim of the present article was to present the experience in liver graft use during the first year of work of a local evaluation and procurement team. MATERIALS AND METHODS We reviewed the organ donation report forms and allocation offer records covering the time frame of December 15, 2017 to December 15, 2018, and registered the donor characteristics, causes of organ discard, causes of declined offers, transport time, and graft and recipient survival at 30 days. RESULTS There were 17 donations and we completed the evaluation of 14. Two donors were considered ideal (14.2%) and 12 were expanded criteria donors (ECDs) (85.7%). Two grafts with steatosis were not offered (14.2%). Twelve liver grafts were offered 88 times (mean 7.6 offers per graft). The acceptance rate was 6% for public hospitals and 23.6% for private hospitals (p = 0.016). One graft was discarded during the procurement process due to steatosis. The rate of use after evaluation was 78.5% (11/14). All the grafts were procured by the local team and 9 (81.8%) were transported by commercial airline (median 240 min, range 85 min). Graft and recipient survival at 30 days was 100%. CONCLUSIONS The participation of a local evaluation and procurement team notably increased liver graft use with excellent results. Commercial airline transportation of the grafts to all active transplantation centers of the country resulted in cold ischemia times <6 h.
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Affiliation(s)
- D Zamora-Valdés
- Grupo de Estudio de Trasplante Hepático México, Hospital Ángeles Acoxpa, Mexico City, Mexico.
| | - P Leal-Leyte
- Grupo de Estudio de Trasplante Hepático México, Hospital Ángeles Acoxpa, Mexico City, Mexico
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Chen M, Chen Z, Lin X, Hong X, Ma Y, Huang C, He X, Ju W. Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers - a retrospective study. Transpl Int 2021; 34:1261-1270. [PMID: 33484201 PMCID: PMC8361689 DOI: 10.1111/tri.13828] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 12/21/2020] [Accepted: 01/19/2021] [Indexed: 12/20/2022]
Abstract
The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia‐free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3‐year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.
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Affiliation(s)
- Maogen Chen
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zhitao Chen
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaohong Lin
- Division of General Surgery, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xitao Hong
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Yihao Ma
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Changjun Huang
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Weiqiang Ju
- Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.,Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
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50
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Lozanovski VJ, Probst P, Arefidoust A, Ramouz A, Aminizadeh E, Nikdad M, Khajeh E, Ghamarnejad O, Shafiei S, Ali-Hasan-Al-Saegh S, Seide SE, Kalkum E, Nickkholgh A, Czigany Z, Lurje G, Mieth M, Mehrabi A. Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation. Transpl Int 2021; 34:778-800. [PMID: 33728724 DOI: 10.1111/tri.13861] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 02/19/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022]
Abstract
This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Alireza Arefidoust
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Mohammadsadegh Nikdad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Saeed Shafiei
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan-Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Svenja E Seide
- Institute of Medical Biometry and Informatics (IMBI), University of Heidelberg, Heidelberg, Germany
| | - Eva Kalkum
- The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arash Nickkholgh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Georg Lurje
- Department of Surgery, Charité -Universitätsmedizin Berlin, Berlin, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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