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Jeddou H, Tzedakis S, Chaouch MA, Sulpice L, Samson M, Boudjema K. Viability Assessment During Normothermic Machine Liver Perfusion: A Literature Review. Liver Int 2025; 45:e16244. [PMID: 39821671 PMCID: PMC11740183 DOI: 10.1111/liv.16244] [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: 06/30/2024] [Revised: 12/25/2024] [Accepted: 01/03/2025] [Indexed: 01/19/2025]
Abstract
BACKGROUND AND OBJECTIVE The discrepancy between donor organ availability and demand leads to a significant waiting-list dropout rate and mortality. Although quantitative tools such as the Donor Risk Index (DRI) help assess organ suitability, many potentially viable organs are still discarded due to the lack of universally accepted markers to predict post-transplant outcomes. Normothermic machine perfusion (NMP) offers a platform to assess viability before transplantation. Thus, livers considered unsuitable for transplantation based on the DRI can be evaluated and potentially transplanted. During NMP, various viability criteria have been proposed. These criteria are neither homogeneous nor consensual. In this review, we aimed to describe the viability criteria during NMP and evaluate their ability to predict hepatic graft function following transplantation. We conducted a PubMed search using the terms 'liver transplantation', 'normothermic machine perfusion' and 'assessment', including only English publications up to February 2024. Viability assessment during NMP includes multiple hepatocellular and cholangiocellular criteria. Lactate clearance and bile production are commonly used indicators, but their ability to predict post-transplant outcomes varies significantly. The predictive value of cholangiocellular criteria such as bile pH, bicarbonate and glucose levels remains under investigation. Novel markers, such as microRNAs and proteomic profiles, offer the potential to enhance graft evaluation accuracy and provide insights into the molecular mechanisms underlying liver viability. Combining perfusion parameters with biomarkers may improve the prediction of long-term graft survival. Future research should focus on standardising viability assessment protocols and exploring real-time biomarker evaluations, which could enhance transplantation outcomes and expand the donor pool.
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Affiliation(s)
- Heithem Jeddou
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
| | - Stylianos Tzedakis
- Department of Hepato‐Biliary, Digestive and Endocrine SurgeryCochin Hospital, APHPParisFrance
- Université Paris CitéParisFrance
| | - Mohamed Ali Chaouch
- Department of Visceral and Digestive SurgeryMonastir University HospitalMonastirTunisia
| | - Laurent Sulpice
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- INSERM OSS U1242, University Hospital, Rennes 1 UniversityRennesFrance
| | - Michel Samson
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive SurgeryUniversity Hospital, Rennes 1 UniversityRennesFrance
- Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)‐UMR_S 1085, Université de RennesRennesFrance
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Robinson T, Vargas PA, Yemini R, Goldaracena N, Pelletier S. Are we on track to increase organ utilization? An analysis of machine perfusion preservation for liver transplantation in the United States. Artif Organs 2024; 48:1275-1287. [PMID: 39034871 DOI: 10.1111/aor.14812] [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: 01/09/2024] [Revised: 05/17/2024] [Accepted: 06/11/2024] [Indexed: 07/23/2024]
Abstract
BACKGROUND Efforts to improve the quality of marginal grafts for transplantation are essential. Machine perfusion preservation appears as a promising solution. METHODS The United Network for Organ Sharing (UNOS) database was queried for deceased liver donor records between 2016 and 2022. The primary outcome of interest was the organ nonutilization rate. Long-term graft and patient survival among extended criteria donors (ECDs) were also analyzed. RESULTS During the study period, out of 54 578 liver grafts recovered for transplant, 5085 (9.3%) were nonutilized. Multivariable analysis identified normothermic machine perfusion (NMP) preservation as the only predictor associated with a reduction in graft nonutilization (OR = 0.12; 95% CI = 0.06-0.023, p < 0.001). Further analysis of ECD grafts that were transplanted revealed comparable 1-,2- and 3-years graft survival (89%/88%/82% vs. 90%/85%/81%, p = 0.60), and patient survival (92%/91%/84% vs. 92%/88%/84%, p = 0.65) between grafts that underwent MP vs. those who did not, respectively. CONCLUSIONS Liver nonutilization rates in the United States are at an all-time high. Available data, most likely including cases from clinical trials, showed that NMP reduced the odds of organ nonutilization by 12% among the entire deceased donor pool and by 16% among grafts from ECD. Collective efforts and further evidence reflecting day-to-day clinical practice are needed to fully reach the potential of MP for liver transplant.
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Affiliation(s)
- Todd Robinson
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Paola A Vargas
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Renana Yemini
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Nicolas Goldaracena
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Shawn Pelletier
- Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia, USA
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Groen PC, van Leeuwen OB, de Jonge J, Porte RJ. Viability assessment of the liver during ex-situ machine perfusion prior to transplantation. Curr Opin Organ Transplant 2024; 29:239-247. [PMID: 38764406 PMCID: PMC11224566 DOI: 10.1097/mot.0000000000001152] [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] [Indexed: 05/21/2024]
Abstract
PURPOSE OF REVIEW In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function. RECENT FINDINGS Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy. SUMMARY Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.
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Affiliation(s)
- Puck C Groen
- Department of Surgery, Division of Hepato-Pancreato- Biliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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Abstract
OBJECTIVE To define benchmark cutoffs for redo liver transplantation (redo-LT). BACKGROUND In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. METHODS We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. RESULTS Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks. CONCLUSION This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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Machine Learning Prediction of Liver Allograft Utilization From Deceased Organ Donors Using the National Donor Management Goals Registry. Transplant Direct 2021; 7:e771. [PMID: 34604507 PMCID: PMC8478404 DOI: 10.1097/txd.0000000000001212] [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: 05/18/2021] [Accepted: 06/08/2021] [Indexed: 11/25/2022] Open
Abstract
Early prediction of whether a liver allograft will be utilized for transplantation may allow better resource deployment during donor management and improve organ allocation. The national donor management goals (DMG) registry contains critical care data collected during donor management. We developed a machine learning model to predict transplantation of a liver graft based on data from the DMG registry. Methods Several machine learning classifiers were trained to predict transplantation of a liver graft. We utilized 127 variables available in the DMG dataset. We included data from potential deceased organ donors between April 2012 and January 2019. The outcome was defined as liver recovery for transplantation in the operating room. The prediction was made based on data available 12-18 h after the time of authorization for transplantation. The data were randomly separated into training (60%), validation (20%), and test sets (20%). We compared the performance of our models to the Liver Discard Risk Index. Results Of 13 629 donors in the dataset, 9255 (68%) livers were recovered and transplanted, 1519 recovered but used for research or discarded, 2855 were not recovered. The optimized gradient boosting machine classifier achieved an area under the curve of the receiver operator characteristic of 0.84 on the test set, outperforming all other classifiers. Conclusions This model predicts successful liver recovery for transplantation in the operating room, using data available early during donor management. It performs favorably when compared to existing models. It may provide real-time decision support during organ donor management and transplant logistics.
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Brüggenwirth IMA, Werner MJM, Adam R, Polak WG, Karam V, Heneghan MA, Mehrabi A, Klempnauer JL, Paul A, Mirza DF, Pratschke J, Salizzoni M, Cherqui D, Allison M, Soubrane O, Staffa SJ, Zurakowski D, Porte RJ, de Meijer VE. The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation. Transpl Int 2021; 34:1928-1937. [PMID: 34160850 PMCID: PMC8518385 DOI: 10.1111/tri.13956] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 04/27/2021] [Accepted: 06/18/2021] [Indexed: 01/10/2023]
Abstract
High‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high‐risk combinations of recipient‐ and graft‐related factors prognostic for long‐term graft survival after reLT. This tool may serve as a guidance for clinical decision‐making on liver acceptance for reLT.
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Affiliation(s)
- Isabel M A Brüggenwirth
- Division of HPB Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Maureen J M Werner
- Division of HPB Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - René Adam
- Centre Hépato-Biliaire, Inserm U935, Hôpital Universitaire Paul Brousse, Villejuif, France
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Vincent Karam
- Centre Hépato-Biliaire, Inserm U935, Hôpital Universitaire Paul Brousse, Villejuif, France
| | | | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, Medical University Heidelberg, University Hospital, Heidelberg, Germany
| | - Jürgen L Klempnauer
- Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Andreas Paul
- Department of General, Visceral and Transplantation Surgery, Essen University Hospital, Essen, Germany
| | - Darius F Mirza
- Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Mauro Salizzoni
- General Surgery 2U - Liver Transplant Unit, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Daniel Cherqui
- Department of Surgery, Centre Hépato-Biliare, Inserm, Unit 1193, Paul-Brousse Hospital, Villejuif, France
| | - Michael Allison
- Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge, UK
| | - Olivier Soubrane
- Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France
| | - Steven J Staffa
- Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA
| | - David Zurakowski
- Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA
| | - Robert J Porte
- Division of HPB Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Vincent E de Meijer
- Division of HPB Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Zhang Z, Ju W, Tang Y, Wang L, Zhu C, Gao N, Zhao Q, Huang S, Wang D, Yang L, Han M, Xiong W, Wu L, Chen M, Zhang Y, Zhu Y, Sun C, Zhu X, Guo Z, He X. First Preliminary Experience with Preservation of Liver Grafts from Extended-Criteria Donors by Normothermic Machine Perfusion in Asia. Ann Transplant 2020; 25:e921529. [PMID: 32312947 PMCID: PMC7193227 DOI: 10.12659/aot.921529] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/24/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Normothermic machine perfusion (NMP) can provide access to evaluate and resuscitate high-risk donor livers before transplantation. The purpose of this study was to determine the efficacy of NMP in preservation and assessment of extended-criteria donor (ECD) livers in China. CASE REPORT From September 2018 to March 2019, 4 liver grafts from 3 transplant center defined as ECD were subjected to NMP, and then were transplanted successfully. During perfusion, perfusion parameters such as vascular flow, glucose level, lactate clearance, and bile production/composition were recorded to assess graft viability. All recipients were followed up 6 months after transplantation. CONCLUSIONS NMP provides a potential tool for preservation and assessment of ECD livers in China.
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Affiliation(s)
- Zhiheng Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Weiqiang Ju
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Yunhua Tang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Linhe Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Caihui Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Ningxin Gao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Qiang Zhao
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Shanzhou Huang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Dongping Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Lu Yang
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Ming Han
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Wei Xiong
- Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Linwei Wu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Maogen Chen
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Yixi Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Yanling Zhu
- Department of Cardiopulmonary Bypass, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
| | - Chengjun Sun
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, P.R. China
- Organ Transplant Center, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, Guangdong, P.R. China
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9
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Czigany Z, Lurje I, Schmelzle M, Schöning W, Öllinger R, Raschzok N, Sauer IM, Tacke F, Strnad P, Trautwein C, Neumann UP, Fronek J, Mehrabi A, Pratschke J, Schlegel A, Lurje G. Ischemia-Reperfusion Injury in Marginal Liver Grafts and the Role of Hypothermic Machine Perfusion: Molecular Mechanisms and Clinical Implications. J Clin Med 2020; 9:E846. [PMID: 32244972 PMCID: PMC7141496 DOI: 10.3390/jcm9030846] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 03/09/2020] [Accepted: 03/11/2020] [Indexed: 12/19/2022] Open
Abstract
Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP-which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion-will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.
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Affiliation(s)
- Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (Z.C.); (U.P.N.)
| | - Isabella Lurje
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Moritz Schmelzle
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Wenzel Schöning
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Robert Öllinger
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Nathanael Raschzok
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Igor M. Sauer
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany;
| | - Pavel Strnad
- Department of Gastroenterology, Metabolic Disorders and Intensive Care, University Hospital RWTH Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Christian Trautwein
- Department of Gastroenterology, Metabolic Disorders and Intensive Care, University Hospital RWTH Aachen, 52074 Aachen, Germany; (P.S.); (C.T.)
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (Z.C.); (U.P.N.)
| | - Jiri Fronek
- Department of Transplant Surgery, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic;
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, 69120 Heidelberg, Germany;
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
| | - Andrea Schlegel
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK;
| | - Georg Lurje
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (Z.C.); (U.P.N.)
- Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum—Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany; (I.L.); (M.S.); (W.S.); (R.Ö.); (N.R.); (I.M.S.); (J.P.)
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10
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Glycocalyx Damage Within Human Liver Grafts Correlates With Graft Injury and Postoperative Graft Function After Orthotopic Liver Transplantation. Transplantation 2020; 104:72-78. [DOI: 10.1097/tp.0000000000002838] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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11
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de Vries Y, Berendsen TA, Fujiyoshi M, van den Berg AP, Blokzijl H, de Boer MT, van der Heide F, de Kleine RHJ, van Leeuwen OB, Matton APM, Werner MJM, Lisman T, de Meijer VE, Porte R. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial). BMJ Open 2019; 9:e028596. [PMID: 31420387 PMCID: PMC6701560 DOI: 10.1136/bmjopen-2018-028596] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
INTRODUCTION Extended criteria donor (ECD) livers are increasingly accepted for transplantation in an attempt to reduce the gap between the number of patients on the waiting list and the available number of donor livers. ECD livers; however, carry an increased risk of developing primary non-function (PNF), early allograft dysfunction (EAD) or post-transplant cholangiopathy. Ischaemia-reperfusion injury (IRI) plays an important role in the development of these complications. Machine perfusion reduces IRI and allows for reconditioning and subsequent evaluation of liver grafts. Single or dual hypothermic oxygenated machine perfusion (DHOPE) (4°C-12°C) decreases IRI by resuscitation of mitochondria. Controlled oxygenated rewarming (COR) may further reduce IRI by preventing sudden temperature shifts. Subsequent normothermic machine perfusion (NMP) (37°C) allows for ex situ viability assessment to facilitate the selection of ECD livers with a low risk of PNF, EAD or post-transplant cholangiopathy. METHODS AND ANALYSIS This prospective, single-arm study is designed to resuscitate and evaluate initially nationwide declined ECD livers. End-ischaemic DHOPE will be performed for the initial mitochondrial and graft resuscitation, followed by COR of the donor liver to a normothermic temperature. Subsequently, NMP will be continued to assess viability of the liver. Transplantation into eligible recipients will proceed if all predetermined viability criteria are met within the first 150 min of NMP. To facilitate machine perfusion at different temperatures, a perfusion solution containing a haemoglobin-based oxygen carrier will be used. With this protocol, we aim to transplant extra livers. The primary endpoint is graft survival at 3 months after transplantation. ETHICS AND DISSEMINATION This protocol was approved by the medical ethical committee of Groningen, METc2016.281 in August 2016 and registered in the Dutch Trial registration number TRIAL REGISTRATION NUMBER: NTR5972, NCT02584283.
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Affiliation(s)
- Yvonne de Vries
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Tim A Berendsen
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Masato Fujiyoshi
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Aad P van den Berg
- Gasteroenterology and Hepatology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
| | - Hans Blokzijl
- Gasteroenterology and Hepatology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
| | - Marieke T de Boer
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Frans van der Heide
- Gasteroenterology and Hepatology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
| | - Ruben H J de Kleine
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Otto B van Leeuwen
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Alix P M Matton
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maureen J M Werner
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Robert Porte
- Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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12
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Minimizing Risk Associated With Older Liver Donors by Matching to Preferred Recipients: A National Registry and Validation Study. Transplantation 2019; 102:1514-1519. [PMID: 29570165 DOI: 10.1097/tp.0000000000002190] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Allografts from older liver donors (OLDs), 70 years or older are often discarded for fear of inferior outcomes. We previously identified "preferred recipients" who did not suffer the higher risk of graft loss and mortality associated with OLDs. Preferred recipients were first-time, non-status 1 registrants older than 45 years, body mass index less than 35, indication other than hepatitis C, and cold ischemia time less than 8 hours. METHODS We assessed the validity of the preferred recipient construct in a larger, more recent cohort (38 891 patients, 2006-2013). We compared recipients of OLD grafts to recipients of average liver donors (ALDs, age = 40-69) and ideal liver donors (ILDs, age = 18-39) grafts using multilevel Cox regression adjusting for recipient and transplant factors. RESULTS The use of OLD grafts in preferred recipients has increased from 2006 to 2013 (P = 0.02). Preferred recipients Model for End-Stage Liver Disease scores ranged 6 to 40. Preferred recipients had similar 5-year all-cause graft loss (ACGL) with OLD versus ALD and ILD grafts (25.4% vs 24.5% and 21.6%). Conversely, nonpreferred recipients had higher 5-year ACGL with OLD versus ALD and ILD grafts (41.4% vs 32.9% and 25.6%). After adjustment, preferred recipients had similar graft loss with OLD versus ALD grafts (hazard ratio [HR], 0.921.081.27; P = 0.3) and ILD grafts (HR, 0.981.161.39, P = 0.09); however, nonpreferred recipients had higher ACGL risk with OLD grafts versus ALD (HR, 1.281.411.56, P < 0.001) and ILD grafts (HR, 1.501.671.86, P < 0.001). Similar trends are seen with mortality. CONCLUSIONS Because preferred recipients comprise 43.3% (n = 2916) of the current waitlist and span the full range of Model for End-Stage Liver Disease scores, transplanted OLD allografts could be distributed without added risk of graft loss or mortality.
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13
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Akateh C, Beal EW, Kim JL, Reader BF, Maynard K, Zweier JL, Whitson BA, Black SM. Intrahepatic Delivery of Pegylated Catalase Is Protective in a Rat Ischemia/Reperfusion Injury Model. J Surg Res 2019; 238:152-163. [PMID: 30771685 DOI: 10.1016/j.jss.2019.01.028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/27/2018] [Accepted: 01/10/2019] [Indexed: 01/03/2023]
Abstract
BACKGROUND Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exogenous PEG-CAT has been only mildly therapeutic for hepatic IRI. Here, we investigated the protective effects of direct intrahepatic delivery of PEG-CAT during IRI using a rat hilar clamp model. MATERIALS AND METHODS PEG-CAT was tested in vitro and in vivo. In vitro, enriched rat liver cell populations were subjected to oxidative stress injury (H2O2), and measures of cell health and viability were assessed. In vivo, rats underwent segmental (70%) hepatic warm ischemia for 1 h, followed by 6 h of reperfusion, and plasma alanine aminotransferase and aspartate aminotransferase, tissue malondialdehyde, adenosine triphosphate, and GSH, and histology were assessed. RESULTS In vitro, PEG-CAT pretreatment of liver cells showed substantial uptake and protection against oxidative stress injury. In vivo, direct intrahepatic, but not systemic, delivery of PEG-CAT during IRI significantly reduced alanine aminotransferase and aspartate aminotransferase in a time-dependent manner (P < 0.01, P < 0.0001, respectively, for all time points) compared to control. Similarly, tissue malondialdehyde (P = 0.0048), adenosine triphosphate (P = 0.019), and GSH (P = 0.0015), and the degree of centrilobular necrosis, were improved by intrahepatic compared to systemic PEG-CAT delivery. CONCLUSIONS Direct intrahepatic administration of PEG-CAT achieved significant protection against IRI by reducing the volume distribution and taking advantage of the substantial hepatic first-pass uptake of this molecule. The mode of delivery was an important factor for protection against hepatic IRI by PEG-CAT.
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Affiliation(s)
- Clifford Akateh
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio; Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Eliza W Beal
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio; Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jung-Lye Kim
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Brenda F Reader
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio; Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Katelyn Maynard
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jay L Zweier
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Bryan A Whitson
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio; Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sylvester M Black
- The COPPER Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio; Comprehensive Transplant Center, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.
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14
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Lei M, Yan LN, Yang JY, Wen TF, Li B, Wang WT, Wu H, Xu MQ, Chen ZY, Wei YG. Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China. World J Gastroenterol 2018; 24:5525-5536. [PMID: 30622380 PMCID: PMC6319134 DOI: 10.3748/wjg.v24.i48.5525] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 12/08/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.
AIM To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients.
METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.
RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative (HBcAb-) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg+) and HBsAg negative (HBsAg-) patients.
Newly diagnosed HBV infection had a relatively higher incidence in HBsAg- patients with HBcAb+ liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival (P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks.
CONCLUSION HBcAb+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.
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Affiliation(s)
- Ming Lei
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lu-Nan Yan
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Tian-Fu Wen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Li
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Tao Wang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong Wu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ming-Qing Xu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhe-Yu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yong-Gang Wei
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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15
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Akateh C, Beal EW, Whitson BA, Black SM. Normothermic Ex-vivo Liver Perfusion and the Clinical Implications for Liver Transplantation. J Clin Transl Hepatol 2018; 6:276-282. [PMID: 30271739 PMCID: PMC6160298 DOI: 10.14218/jcth.2017.00048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 02/07/2018] [Accepted: 03/01/2018] [Indexed: 12/13/2022] Open
Abstract
Despite significant improvements in outcomes after liver transplantation, many patients continue to die on the waiting list, while awaiting an available organ for transplantation. Organ shortage is not only due to an inadequate number of available organs, but also the inability to adequately assess and evaluate these organs prior to transplantation. Over the last few decades, ex-vivo perfusion of the liver has emerged as a useful technique for both improved organ preservation and assessment of organs prior to transplantation. Large animal studies have shown the superiority of ex-vivo perfusion over cold static storage. However, these studies have not, necessarily, been translatable to human livers. Small animal studies have been essential in understanding and improving this technology. Similarly, these results have yet to be translated into clinical use. A few Phase 1 clinical trials have shown promise and confirmed the viability of this technology. However, more robust studies are needed before ex-vivo liver perfusion can be widely accepted as the new clinical standard of organ preservation. Here, we aimed to review all relevant large and small animal research, as well as human liver studies on normothermic ex-vivo perfusion, and to identify areas of deficiency and opportunities for future research endeavors.
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Affiliation(s)
- Clifford Akateh
- General and Gastrointestinal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- *Correspondence to: Clifford Akateh, General and Gastrointestinal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, 395 W 12th Ave, Room 654, Columbus, OH-43210-1267, USA. Tel: +1-614-293-8704, Fax: +1-614-293-4063, E-mail:
| | - Eliza W. Beal
- General and Gastrointestinal Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Bryan A. Whitson
- Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Sylvester M. Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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16
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Roullet S, Defaye M, Quinart A, Adam JP, Chiche L, Laurent C, Neau-Cransac M. Liver Transplantation With Old Grafts: A Ten-Year Experience. Transplant Proc 2018; 49:2135-2143. [PMID: 29149974 DOI: 10.1016/j.transproceed.2017.07.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 06/18/2017] [Accepted: 07/30/2017] [Indexed: 02/09/2023]
Abstract
BACKGROUND The persistent scarcity of donors has prompted liver transplantation teams to find solutions for increasing graft availability. We report our experience of liver transplantations performed with grafts from older donors, specifically over 70 and 80 years old. PATIENTS AND METHODS We analyzed our prospectively maintained single-center database from January 1, 2005, to December 31, 2014, with 380 liver transplantations performed in 354 patients. Six groups were composed according to donor age: <40 (n = 84), 40 to 49 (n = 67), from 50 to 59 (n = 62), from 60 to 69 (n = 76), from 70 to 79 (n = 64), and ≥80 years (n = 27). RESULTS Donors <40 years of age had a lower body mass index, died more often from trauma, and more often had cardiac arrest and high transaminase levels. In contrast, older donors (≥70 years of age) died more often from stroke. Recipients of grafts from donors <50 years of age were more frequently infected by hepatitis C virus; recipients of oldest grafts more often had hepatocellular carcinoma. Cold ischemia time was the shortest in donors >80 years of age. Patient survival was not significantly different between the groups. In multivariate analysis, factors predicting graft loss were transaminase peak, retransplantation and cold ischemia time but not donor age. CONCLUSIONS Older donors >70 and >80 years of age could provide excellent liver grafts.
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Affiliation(s)
- S Roullet
- Department of Anesthesia and Intensive Care and Liver Transplantation Unit, Bordeaux, France; Inserm UMR 12-11, Bordeaux, France.
| | - M Defaye
- Department of Anesthesia and Intensive Care and Liver Transplantation Unit, Bordeaux, France
| | - A Quinart
- Department of Anesthesia and Intensive Care and Liver Transplantation Unit, Bordeaux, France
| | - J-P Adam
- Department of Digestive Surgery and Liver Transplantation Unit, CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France
| | - L Chiche
- Department of Digestive Surgery and Liver Transplantation Unit, CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France
| | - C Laurent
- Department of Digestive Surgery and Liver Transplantation Unit, CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France
| | - M Neau-Cransac
- Department of Hepatology and Liver Transplantation Unit, CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France
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17
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Bral M, Gala-Lopez B, Bigam DL, Freed DH, Shapiro AMJ. Ex situ liver perfusion: Organ preservation into the future. Transplant Rev (Orlando) 2018; 32:132-141. [PMID: 29691119 DOI: 10.1016/j.trre.2018.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 03/27/2018] [Accepted: 03/27/2018] [Indexed: 12/15/2022]
Abstract
In recent years, remarkable progress has occurred in the development of technologies to support ex situ liver perfusion. Building upon extensive preclinical studies in large animal models, pilot and randomized clinical trials have been initiated, and preliminary outcomes suggest more optimal protection of both standard and extended criteria liver grafts. There currently exists an incredible opportunity and need to further refine this technology, determine appropriate viability measures to predict usable liver grafts, and to explore potent protective additive strategies to further optimize the quality of extended criteria organs. These findings will have major bearing in expanding the limited liver donor pool, and may save lives where up to a quarter of listed patients die on wait-lists. Herein we offer a brief overview of the history and current status of ex situ liver perfusion, and discuss future directions that will likely have major impact on the practice of clinical liver transplantation.
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Affiliation(s)
- Mariusz Bral
- Department of Surgery, University of Alberta, 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada; Members of the Canadian National Transplant Research Program (CNTRP), 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada.
| | - Boris Gala-Lopez
- Department of Surgery, University of Alberta, 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada; Members of the Canadian National Transplant Research Program (CNTRP), 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada.
| | - David L Bigam
- Department of Surgery, University of Alberta, 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada; Members of the Canadian National Transplant Research Program (CNTRP), 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada.
| | - Darren H Freed
- Department of Surgery, University of Alberta, 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada; Members of the Canadian National Transplant Research Program (CNTRP), 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada.
| | - A M James Shapiro
- Department of Surgery, University of Alberta, 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada; Members of the Canadian National Transplant Research Program (CNTRP), 2D4.43 Walter D MacKenzie Health Sciences Centre, 8440 112 St, Edmonton, Alberta T6G2B7, Canada.
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18
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Memeo R, de'Angelis N, Salloum C, Compagnon P, Laurent A, Feray C, Duvoux C, Azoulay D. Clinical outcomes of right-lobe split-liver versus orthotopic liver transplants from donors more than 70 years old. Prog Transplant 2018; 25:243-50. [PMID: 26308784 DOI: 10.7182/pit2015303] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Context-The imbalance between the organ supply and the number of potential transplant recipients led to consideration of expanded-criteria liver donors. Objective-To compare right-lobe split-liver transplants (RL-SLTs) with orthotopic liver transplants (OLTs) from donors more than 70 years old (OLT-O) and OLTs from donors less than 55 years old (OLT-Y). Methods-Seventy-one patients who received an RL-SLT were matched for age, sex, and Model for End-stage Liver Disease score with 71 patients who underwent OLT-O and 142 patients who underwent OLT-Y. Clinical outcomes were compared between groups. Results-Longer operation time was associated with RL-SLT (P< .001) as well as more blood loss (P= .03) and transfusions (P= .05). Postoperative morbidity was less in the OLT-Y group, with a lower rate of grades III to IV Clavien-Dindo complication (30%), compared with values in OLT-O (52%) and RL-SLT (38%). Kaplan-Meier analysis demonstrated better 1-year and 3-year survival rates in the OLT-Y group (97% and 92%, respectively), compared with 92% and 86.3%, respectively, in the RL-SLT group; and 84.5% and 73%, respectively, in the OLT-O group (P = .03). Kaplan-Meier analysis also demonstrated differences between the groups in terms of 1-year and 3-year graft survival rates, which were 92% and 86%, respectively, in OLT-Y; 77% and 66%, respectively, in the OLT-O, and 84.2% and 76.6%, respectively, in the RL-SLT group (P= .01). Conclusion-Even if OLT-Y guarantees better patient and graft survival, both RL-SLT and OLT-O can be used safely to expand the pool of liver donors, showing acceptable clinical results and complications rates.
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Affiliation(s)
- Riccardo Memeo
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Nicola de'Angelis
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Chady Salloum
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Philipe Compagnon
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Alexis Laurent
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Cyrille Feray
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Cristoph Duvoux
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
| | - Daniel Azoulay
- Hospital Henri-Mondor, Université de Paris Est-Creteil, Paris, France
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19
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Clavien PA, Dutkowski P. Advances in hypothermic perfusion. Liver Transpl 2017; 23:S52-S55. [PMID: 28815993 DOI: 10.1002/lt.24844] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 08/04/2017] [Accepted: 08/08/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Pierre-Alain Clavien
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
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20
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Ezekian B, Mulvihill MS, Freischlag K, Yerokun BA, Davis RP, Hartwig MG, Knechtle SJ, Barbas AS. Elevated HbA1c in donor organs from patients without a diagnosis of diabetes portends worse liver allograft survival. Clin Transplant 2017; 31. [PMID: 28667782 DOI: 10.1111/ctr.13047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2017] [Indexed: 11/26/2022]
Abstract
Recipients of liver allografts from diabetic donors have decreased graft survival. However, limited data exist on the effects of donor HbA1c. We hypothesized that allografts from nondiabetic donors with elevated HbA1c would be associated with decreased survival. Liver transplant recipients from the UNOS database from nondiabetic donors were stratified into two groups: euglycemic (HbA1c<6.5) and hyperglycemic (HbA1c≥6.5). Propensity score matching (10:1) was used to adjust for donor and recipient characteristics. Kaplan-Meier analysis was used to assess survival. Donors of hyperglycemic allografts were older (49 vs 36, P<.001), were more likely to be non-white, had a higher BMI (29.8 vs 26.2, P<.001), were more likely to engage in heavy cigarette use (1.5% vs 1.3%, P=.004), had higher serum creatinine levels (1.3 vs 1.0, P=.002), and were more likely to be an expanded-criteria donor (35.8% vs 14.4%, P<.001). After propensity matching to account for these differences, allograft survival was significantly decreased in the recipients of hyperglycemic allografts (P=.049), and patient survival showed a trend toward reduction (P=.082). These findings suggest that HbA1c may be a simple and inexpensive test with potential utility for better organ risk stratification.
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Affiliation(s)
- Brian Ezekian
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Kyle Freischlag
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Robert P Davis
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Matthew G Hartwig
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Stuart J Knechtle
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
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21
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Selten JW, Verhoeven CJ, Heedfeld V, Roest HP, de Jonge J, Pirenne J, van Pelt J, Ijzermans JNM, Monbaliu D, van der Laan LJW. The release of microRNA-122 during liver preservation is associated with early allograft dysfunction and graft survival after transplantation. Liver Transpl 2017; 23:946-956. [PMID: 28388830 DOI: 10.1002/lt.24766] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 02/27/2017] [Accepted: 03/07/2017] [Indexed: 12/24/2022]
Abstract
Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult because of the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable, and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical LT and in an experimental DCD model. Graft preservation solutions of 83 liver grafts at the end of cold ischemia were analyzed for miRNAs by reverse transcription polymerase chain reaction. Of these grafts, 42% developed EAD after transplantation. Results were verified in pig livers (n = 36) exposed to different lengths of warm ischemia time (WIT). The absolute miR-122 levels and miR-122/miR-222 ratios in preservation fluids were significantly higher in DCD grafts (P = 0.001) and grafts developing EAD (P = 0.004). In concordance, the miR-122/miR-222 ratios in perfusion fluid correlate with serum transaminase levels within the first 24 hours after transplantation. Longterm graft survival was significantly diminished in grafts with high miR-122/miR-222 ratios (P = 0.02). In the porcine DCD model, increased WIT lead to higher absolute miR-122 levels and relative miR-122/miR-222 ratios in graft perfusion fluid (P = 0.01 and P = 0.02, respectively). High miR-122/miR-222 ratios in pig livers were also associated with high aspartate aminotransferase levels after warm oxygenated reperfusion. In conclusion, both absolute and relative miR-122 levels in graft preservation solution are associated with DCD, EAD, and early graft loss after LT. As shown in a porcine DCD model, miRNA release correlated with the length of WITs. Liver Transplantation 23 946-956 2017 AASLD.
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Affiliation(s)
- Jasmijn W Selten
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
| | - Cornelia J Verhoeven
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
| | - Veerle Heedfeld
- Abdominal Transplant Surgery, Department of Surgery, Catholic University of Leuven, Leuven, Belgium
| | - Henk P Roest
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
| | - Jacques Pirenne
- Abdominal Transplant Surgery, Department of Surgery, Catholic University of Leuven, Leuven, Belgium
| | - Jos van Pelt
- Laboratory of Hepatology, Department of Clinical and Experimental Medicine, Liver Research Facility, Catholic University of Leuven, Leuven, Belgium
| | - Jan N M Ijzermans
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
| | - Diethard Monbaliu
- Abdominal Transplant Surgery, Department of Surgery, Catholic University of Leuven, Leuven, Belgium
| | - Luc J W van der Laan
- Department of Surgery, Erasmus Medical Center-University Medical Center, Rotterdam, the Netherlands
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22
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Abstract
The demand of donor livers for transplantation exceeds the supply. In an attempt to maximize the number of potentially usable donor livers, several centers are exploring the role of machine perfusion. This review provides an update on machine perfusion strategies and basic concepts, based on current clinical issues, and discuss challenges, including currently used biomarkers for assessing the quality and viability of perfused organs. The potential benefits of machine perfusion on immunogenicity and the consequences on post-operative immunosuppression management are discussed.
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23
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Rayar M, Levi Sandri GB, Cusumano C, Locher C, Houssel-Debry P, Camus C, Lombard N, Desfourneaux V, Lakehal M, Meunier B, Sulpice L, Boudjema K. Benefits of temporary portocaval shunt during orthotopic liver transplantation with vena cava preservation: A propensity score analysis. Liver Transpl 2017; 23:174-183. [PMID: 27706895 DOI: 10.1002/lt.24650] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 09/20/2016] [Accepted: 09/26/2016] [Indexed: 02/07/2023]
Abstract
During orthotopic liver transplantation (OLT), clamping of the portal vein induces splanchnic venous congestion and accumulation of noxious compounds. These adverse effects could increase ischemia/reperfusion injury and subsequently the risk of graft dysfunction, especially for grafts harvested from extended criteria donors (ECDs). Temporary portocaval shunt (TPCS) could prevent these complications. Between 2002 and 2013, all OLTs performed in our center were retrospectively analyzed and a propensity score matching analysis was used to compare the effect of TPCS in 686 patients (343 in each group). Patients in the TPCS group required fewer intraoperative transfusions (median number of packed red blood cells-5 versus 6; P = 0.02; median number of fresh frozen plasma-5 versus 6; P = 0.02); had improvement of postoperative biological parameters (prothrombin time, Factor V, international normalized ratio, alkaline phosphatase, and gamma-glutamyltransferase levels); and showed significant reduction of biliary complications (4.7% versus 10.2%; P = 0.006). Survival analysis revealed that TPCS improved 3-month graft survival (94.2% versus 88.6%; P = 0.01) as well as longterm survival of elderly (ie, age > 70 years) donor grafts (P = 0.02). In conclusion, the use of TPCS should be recommended especially when considering an ECD graft. Liver Transplantation 23 174-183 2017 AASLD.
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Affiliation(s)
- Michel Rayar
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
- INSERM, CIC 1414, Rennes, France
- Faculté de Médecine, Université Rennes 1, Rennes, France
| | - Giovanni B Levi Sandri
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Caterina Cusumano
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Clara Locher
- Service de Pharmacologie Clinique et Épidémiologique, Centre Hospitalier Universitaire Rennes, Rennes, France
- INSERM, CIC 1414, Rennes, France
- Faculté de Médecine, Université Rennes 1, Rennes, France
| | - Pauline Houssel-Debry
- Service des Maladies du Foie, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Christophe Camus
- Réanimation Médicale, Centre Hospitalier Universitaire Rennes, Rennes, France
- INSERM, CIC 1414, Rennes, France
| | - Nicolas Lombard
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Veronique Desfourneaux
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Mohamed Lakehal
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Bernard Meunier
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
- Faculté de Médecine, Université Rennes 1, Rennes, France
| | - Laurent Sulpice
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
- INSERM, CIC 1414, Rennes, France
- Faculté de Médecine, Université Rennes 1, Rennes, France
| | - Karim Boudjema
- Service de Chirurgie Hépatobiliaire et Digestive, Centre Hospitalier Universitaire Rennes, Rennes, France
- INSERM, CIC 1414, Rennes, France
- Faculté de Médecine, Université Rennes 1, Rennes, France
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24
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Bruzzone P, Balla A, Quaresima S, Seitaj A, Intini G, Giannarelli D, Paganini AM. Comparison of Two Questionnaires on Informed Consent in "Marginal" Donor Liver. Transplant Proc 2017; 48:359-61. [PMID: 27109955 DOI: 10.1016/j.transproceed.2015.12.053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 12/30/2015] [Indexed: 11/25/2022]
Abstract
The necessity of liver donors has contributed to overcoming the traditional criteria and to propose new ones for the acceptance of livers for transplantation. For this reason expanded or extended criteria donation (ECD) or even overextended criteria for marginal or high-risk organ donors have been developed. Ethical, Legal and Psychological Aspects of Organ Transplantation (ELPAT) and European Liver and Intestine Transplant Association (ELITA) - European Liver Transplantation Registry (ELTR) coordinated the distribution of a previously reported questionnaire that was sent to 53 European liver transplant centers. Criteria were divided based on the response rate. Donor criteria such as steatosis and serum sodium >165 mmol/L, as well as recipient criteria such as previous history of cancer, were not considered contraindications to transplantation in more than 60% of cases. Criteria such as ICU (intensive care unit) stay, body mass index >30, serum bilirubin >3 mg/dL, and HIV infection or critical illness were not considered adequate for transplantation in 30% to 59% of cases. On the other hand, there was no agreement on other extended liver donor and recipient criteria, such as age up to 80 years, serum glutamic oxaloacetic transaminase >90 U/L, serum glutamic pyruvic transaminase >105 U/L, high-risk sex practices, drug users, patients older than 65 years, and patients younger than 65 years, respectively. Criteria such as serum sodium could not be considered ECD criteria. In conclusion, development of more studies and inclusion of more liver transplantation centers are required to confirm these data.
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Affiliation(s)
- P Bruzzone
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy.
| | - A Balla
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy
| | - S Quaresima
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy
| | - A Seitaj
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy
| | - G Intini
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy
| | | | - A M Paganini
- Department of General Surgery, Surgical Specialties and Organ Transplantation "Paride Stefanini," Sapienza University, Rome, Italy
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25
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Neves DB, Rusi MB, Diaz LGG, Salvalaggio P. Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors. ACTA ACUST UNITED AC 2016; 14:567-572. [PMID: 27783749 DOI: 10.1590/s1679-45082016rw3585] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 04/09/2016] [Indexed: 12/11/2022]
Abstract
Primary graft dysfunction is a multifactorial syndrome with great impact on liver transplantation outcomes. This review article was based on studies published between January 1980 and June 2015 and retrieved from PubMed database using the following search terms: "primary graft dysfunction", "early allograft dysfunction", "primary non-function" and "liver transplantation". Graft dysfunction describes different grades of graft ischemia-reperfusion injury and can manifest as early allograft dysfunction or primary graft non-function, its most severe form. Donor-, surgery- and recipient-related factors have been associated with this syndrome. Primary graft dysfunction definition, diagnostic criteria and risk factors differ between studies. RESUMO A disfunção primária do enxerto hepático é uma síndrome multifatorial com grande impacto no resultado do transplante de fígado. Foi realizada uma ampla revisão da literatura, consultando a base de dados PubMed, em busca de estudos publicados entre janeiro de 1980 e junho de 2015. Os termos descritivos utilizados foram: "primary graft dysfunction", "early allograft dysfunction", "primary non-function" e "liver transplantation". A disfunção traduz graus diferentes da lesão de isquemia e reperfusão do órgão, e pode se manifestar como disfunção precoce ou, na forma mais grave, pelo não funcionamento primário do enxerto. Fatores relacionados ao doador, ao transplante e ao receptor contribuem para essa síndrome. Existem definições diferentes na literatura quanto ao diagnóstico e aos fatores de risco associados à disfunção primária.
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Affiliation(s)
- Douglas Bastos Neves
- Hospital Federal dos Servidores do Estado, Rio de Janeiro, RJ, Brazil; Hospital São Vicente de Paulo, Rio de Janeiro, RJ, Brazil.,Programa de Pós-graduação em Ciências da Saúde, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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26
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Blok JJ, Detry O, Putter H, Rogiers X, Porte RJ, van Hoek B, Pirenne J, Metselaar HJ, Lerut JP, Ysebaert DK, Lucidi V, Troisi RI, Samuel U, den Dulk AC, Ringers J, Braat AE. Longterm results of liver transplantation from donation after circulatory death. Liver Transpl 2016; 22:1107-14. [PMID: 27028896 DOI: 10.1002/lt.24449] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 03/05/2016] [Accepted: 03/09/2016] [Indexed: 12/13/2022]
Abstract
Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107-1114 2016 AASLD.
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Affiliation(s)
- Joris J Blok
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, University Hospital of Liège, Liège, Belgium
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Xavier Rogiers
- Department of Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Robert J Porte
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Bart van Hoek
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Jacques Pirenne
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Herold J Metselaar
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jan P Lerut
- Starzl Unit of Abdominal Transplantation, Department of Abdominal Surgery and Transplantation, University Hospitals Saint Luc, Brussels, Belgium
| | - Dirk K Ysebaert
- Department of Hepatobiliary, Transplantation and Endocrine Surgery, Antwerp University Hospital, Antwerp University, Belgium
| | - Valerio Lucidi
- Department of Abdominal Surgery, Hepatobiliary and Liver Transplantation Unit, Erasme Hospital ULB, Brussels, Belgium
| | - Roberto I Troisi
- Department of Surgery, Ghent University Hospital Medical School, Ghent, Belgium
| | - Undine Samuel
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - A Claire den Dulk
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Jan Ringers
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
| | - Andries E Braat
- Department of Surgery, Division of Transplantation, Leiden University Medical Center, Leiden University, Leiden, the Netherlands
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27
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Nure E, Lirosi MC, Frongillo F, Bianco G, Silvestrini N, Fiorillo C, Sganga G, Agnes S. Overextended Criteria Donors: Experience of an Italian Transplantation Center. Transplant Proc 2016; 47:2102-5. [PMID: 26361653 DOI: 10.1016/j.transproceed.2014.11.077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023]
Abstract
The increasing gap between the number of patients who could benefit from liver transplantation and the number of available donors has fueled efforts to maximize the donor pool using marginal grafts that usually were discarded for transplantation. This study included data of all patients who received decreased donor liver grafts between January 2004 and January 2013 (n = 218) with the use of a prospectively collected database. Patients with acute liver failure, retransplantation, pediatric transplantation, and split liver transplantation were excluded. Donors were classified as standard donor (SD), extended criteria donor (ECD), and overextended criteria donor (OECD). The primary endpoints of the study were early allograft primary dysfunction (PDF), primary nonfunction (PNF), and patient survival (PS), whereas incidence of major postoperative complications was the secondary endpoint. In our series we demonstrated that OECD have similar outcome in terms of survival and incidence of complication after liver transplantation as ideal grafts.
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Affiliation(s)
- E Nure
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - M C Lirosi
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy.
| | - F Frongillo
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - G Bianco
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - N Silvestrini
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - C Fiorillo
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - G Sganga
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
| | - S Agnes
- Department of Surgery-Transplantation Service, Catholic University of the Sacred Heart, Policlinico "A. Gemelli," Rome, Italy
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28
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Hoyer DP, Paul A, Saner F, Gallinat A, Mathé Z, Treckmann JW, Schulze M, Kaiser GM, Canbay A, Molmenti E, Sotiropoulos GC. Safely expanding the donor pool: brain dead donors with history of temporary cardiac arrest. Liver Int 2015; 35:1756-63. [PMID: 25522767 DOI: 10.1111/liv.12766] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 12/09/2014] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. METHODS We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. RESULTS We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1-150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. CONCLUSION This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.
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Affiliation(s)
- Dieter P Hoyer
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Andreas Paul
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Fuat Saner
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Anja Gallinat
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Zoltan Mathé
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Juergen W Treckmann
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Maren Schulze
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Gernot M Kaiser
- General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Ali Canbay
- Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Ernesto Molmenti
- Department of Surgery, North Shore University Hospital, Manhasset, NY, USA
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Klinzing S, Brandi G, Stehberger PA, Raptis DA, Béchir M. The combination of MELD score and ICG liver testing predicts length of stay in the ICU and hospital mortality in liver transplant recipients. BMC Anesthesiol 2014; 14:103. [PMID: 25844060 PMCID: PMC4384315 DOI: 10.1186/1471-2253-14-103] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 10/27/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Early prediction of outcome would be useful for an optimal intensive care management of liver transplant recipients. Indocyanine green clearance can be measured non-invasively by pulse spectrophometry and is closely related to liver function. METHODS This study was undertaken to assess the predictive value of a combination of the model of end stage liver disease (MELD) score and early indocyanine plasma disappearance rates (ICG-PDR) for length of stay in the intensive care unit (ICU), length of stay in the hospital and hospital mortality in liver transplant recipients. RESULTS Fifty consecutive liver transplant recipients were included in this post Hoc single-center study. ICG-PDR was determined within 6 hours after ICU admission. Endpoints were length of stay in the ICU, length of hospital stay and hospital mortality. The combination of a high MELD score (MELD >25) and a low ICG-PDR clearance (ICG-PDR < 20%/minute) predicts a significant longer stay in the ICU (p = 0.004), a significant longer stay in the hospital (p < 0.001) and a hospital mortality of 40% vs. 0% (p = 0.003). CONCLUSION The combination of MELD scores and a singular ICG-PDR measurement in the early postoperative phase is an accurate predictor for outcome in liver transplant recipients. This easy-to-assess tool might be valuable for an optimal intensive care management of those patients.
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Affiliation(s)
- Stephanie Klinzing
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
| | - Giovanna Brandi
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
| | - Paul A Stehberger
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
| | - Dimitri A Raptis
- Department of Visceral- and Transplantation Surgery, University Hospital of Zurich, Zurich, Switzerland
| | - Markus Béchir
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland
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Sutton ME, op den Dries S, Karimian N, Weeder PD, de Boer MT, Wiersema-Buist J, Gouw ASH, Leuvenink HGD, Lisman T, Porte RJ. Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PLoS One 2014; 9:e110642. [PMID: 25369327 PMCID: PMC4219693 DOI: 10.1371/journal.pone.0110642] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Accepted: 09/24/2014] [Indexed: 12/23/2022] Open
Abstract
Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37 °C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥ 30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.
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Affiliation(s)
- Michael E. Sutton
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Sanna op den Dries
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Negin Karimian
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Pepijn D. Weeder
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Marieke T. de Boer
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Janneke Wiersema-Buist
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Annette S. H. Gouw
- Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Henri G. D. Leuvenink
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert J. Porte
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- * E-mail:
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31
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Matton APM, Porte RJ. Opportunities for scientific expansion of the deceased donor pool. Liver Transpl 2014; 20 Suppl 2:S5. [PMID: 25219379 DOI: 10.1002/lt.24002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
| | - Robert J Porte
- Professor of Surgery Dept. of HPB Surgery and Liver Transplantation University Medical Center Groningen, Cleveland Clinic, Groningen, The Netherlands
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32
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Bloom MB, Raza S, Bhakta A, Ewing T, Patel M, Ley EJ, Margulies DR, Salim A, Malinoski D. Impact of deceased organ donor demographics and critical care end points on liver transplantation and graft survival rates. J Am Coll Surg 2014; 220:38-47. [PMID: 25458800 DOI: 10.1016/j.jamcollsurg.2014.09.020] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 07/29/2014] [Accepted: 09/08/2014] [Indexed: 12/29/2022]
Abstract
BACKGROUND The criteria for organ acceptance remain inconsistent, which limits the ability to standardize critical care practices. We sought to examine predictors of liver graft use and survival to better guide the selection and management of potential organ donors. STUDY DESIGN A prospective observational study of all donors managed by the 8 organ procurement organizations in United Network for Organ Sharing Region 5 was conducted from July 2008 to March 2011. Critical care end points that reflect the normal hemodynamic, acid-base, respiratory, endocrine, and renal status of the donor were collected at 3 time points. Critical care and demographic data associated with liver transplantation and graft survival rates were first determined using univariate analyses, and then logistic regression was used to identify independent predictors of these two outcomes. RESULTS From 961 donors, 730 (76%) livers were transplanted and 694 (95%) were functioning after 74 ± 73 days of follow-up. After regression analysis, donor BMI (odds ratio [OR] = 0.94), male sex (OR = 1.89), glucose <150 mg/dL (OR = 1.97), lower dopamine dose (OR = 0.95), vasopressin use (OR = 1.95), and ejection fraction >50% (OR = 1.77) remained as independent predictors of liver use. Graft survival was associated with lower donor BMI (OR = 0.91) and sodium levels (OR = 0.95). CONCLUSIONS After controlling for donor age, sex, and BMI, both hemodynamic and endocrine critical care end points were associated with increased liver graft use. Both donor BMI and lower sodium levels during the course of donor management were independently predictive of improved graft survival. These results may help guide the management and selection of potential organ donors after neurologic determination of death.
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Affiliation(s)
- Matthew B Bloom
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Shariq Raza
- Department of Surgery, Temple University Medical Center, Philadelphia, PA
| | | | - Tyler Ewing
- School of Medicine, University of California, Davis, CA
| | - Madhukar Patel
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Eric J Ley
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
| | | | - Ali Salim
- Department of Surgery, Brigham and Women's Hospital, Boston, MA
| | - Darren Malinoski
- Surgical Critical Care Section, Portland Veterans Affairs Medical Center, Portland, OR; Department of Surgery, Oregon Health and Science University, Portland, OR.
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Verhoeven CJ, Farid WRR, de Jonge J, Metselaar HJ, Kazemier G, van der Laan LJW. Biomarkers to assess graft quality during conventional and machine preservation in liver transplantation. J Hepatol 2014; 61:672-84. [PMID: 24798616 DOI: 10.1016/j.jhep.2014.04.031] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 04/11/2014] [Accepted: 04/24/2014] [Indexed: 02/08/2023]
Abstract
A global rising organ shortage necessitates the use of extended criteria donors (ECD) for liver transplantation (LT). However, poor preservation and extensive ischemic injury of ECD grafts have been recognized as important factors associated with primary non-function, early allograft dysfunction, and biliary complications after LT. In order to prevent for these ischemia-related complications, machine perfusion (MP) has gained interest as a technique to optimize preservation of grafts and to provide the opportunity to assess graft quality by screening for extensive ischemic injury. For this purpose, however, objective surrogate biomarkers are required which can be easily determined at time of graft preservation and the various techniques of MP. This review provides an overview and evaluation of biomarkers that have been investigated for the assessment of graft quality and viability testing during different types of MP. Moreover, studies regarding conventional graft preservation by static cold storage (SCS) were screened to identify biomarkers that correlated with either allograft dysfunction or biliary complications after LT and which could potentially be applied as predictive markers during MP. The pros and cons of the different biomaterials that are available for biomarker research during graft preservation are discussed, accompanied with suggestions for future research. Though many studies are currently still in the experimental setting or of low evidence level due to small cohort sizes, the biomarkers presented in this review provide a useful handle to monitor recovery of ECD grafts during clinical MP in the near future.
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Affiliation(s)
- Cornelia J Verhoeven
- Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands
| | - Waqar R R Farid
- Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands
| | - Herold J Metselaar
- Department of Gastroenterology & Hepatology, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.
| | - Geert Kazemier
- Department of Surgery, VU University Medical Center Amsterdam, The Netherlands
| | - Luc J W van der Laan
- Department of Surgery, Erasmus MC - University Medical Center, Rotterdam, The Netherlands
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Yang HT, Chen KF, Lu Q, Wei YG, Li B, Qin Y, Huang WQ. Ultrasonic integrated backscatter in assessing liver steatosis before and after liver transplantation. Hepatobiliary Pancreat Dis Int 2014; 13:402-408. [PMID: 25100125 DOI: 10.1016/s1499-3872(14)60039-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver steatosis affects 20%-30% of adults. Because of the increasing gap between graft supplies and demands, livers with steatosis are frequently used in liver transplantation. But severely steatotic liver grafts are associated with a high risk of intraoperative and postoperative complications. Accurate assessment of fat content of donor livers and monitoring of the extent of steatosis in recipients are required for liver transplantation. The present study aimed to determine the correlation between liver echogenicity and fat content, and to evaluate the use of an ultrasonic integrated backscatter system (IBS) in the assessment of changes in fat content after liver transplantation. METHODS Seventy-nine consecutive patients receiving liver grafts from living donors were evaluated in our center. Of these recipients, 67 survived for more than two years and were included in this study. Each liver graft was evaluated with IBS and ultrasound before operation and the fat content was estimated. The fat content of the grafts in the recipients was again assessed with ultrasound at 18 months after surgery. RESULTS A correlation was detected between each graft's IBS value and its fat content (P=0.001). The IBS value in fatty grafts with various degrees of steatosis was significantly decreased in 3 (P=0.02), 12, 15 and 18 (P=0.001) months after orthotopic liver transplantation. The IBS value returned to normal in all patients in 18 months after liver transplantation. CONCLUSIONS Decreased fat content in steatotic grafts can be observed in all recipients. Ultrasonic IBS is useful in determining the steatotic degree of grafts in donors as well as in monitoring the grafts after liver transplantation.
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Affiliation(s)
- Han-Teng Yang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, China.
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Bruzzone P, Giannarelli D, Adam R. A preliminary European Liver and Intestine Transplant Association-European Liver Transplant Registry study on informed recipient consent and extended criteria liver donation. Transplant Proc 2014; 45:2613-5. [PMID: 24034004 DOI: 10.1016/j.transproceed.2013.07.024] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The European Liver and Intestine Transplant Association (ELITA) and the European Liver Transplant Registry (ELTR) coordinated the distribution to European liver transplantation centers of an electronic questionnaire, developed by the first author, concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients. Completed questionnaires were received from 35 centers. All centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were as follows: steatosis in 33 centers (94%); age up to 80 years in 15 centers (43%); serum sodium >165 mmol/L in 25 centers (71%); intensive care unit (ICU) stay with ventilation longer than 7 days in 17 centers (48%); aspartate aminotransferase (AST) >90 U/L, in 6 centers (17%); body mass index (BMI) >30 in 19 centers (54%); alanine aminotransferase (ALT) >105 U/L in 8 centers (23%); serum bilirubin >3 mg/dL in 15 centers (43%); and all criteria together in 2 centers (6%). Thirty-one centers informed the transplantation candidate of the ECD status of the donor, 20 (65%) when the patient registered for transplantation, 1 (3%) when an ECD liver became available, and 10 centers (32%) on both occasions. Thirteen centers required the liver transplantation candidate to sign a special consent form. Twenty centers informed the potential recipient of the donor's serology. Only 6 centers informed the potential recipient of any high-risk behavior of the donor.
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Affiliation(s)
- P Bruzzone
- Sapienza Università di Roma, "Azienda Policlinico Umberto l", Rome, Italy.
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Vos JJ, Wietasch JKG, Absalom AR, Hendriks HGD, Scheeren TWL. Green light for liver function monitoring using indocyanine green? An overview of current clinical applications. Anaesthesia 2014; 69:1364-76. [PMID: 24894115 DOI: 10.1111/anae.12755] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2014] [Indexed: 12/12/2022]
Abstract
The dye indocyanine green is familiar to anaesthetists, and has been studied for more than half a century for cardiovascular and hepatic function monitoring. It is still, however, not yet in routine clinical use in anaesthesia and critical care, at least in Europe. This review is intended to provide a critical analysis of the available evidence concerning the indications for clinical measurement of indocyanine green elimination as a diagnostic and prognostic tool in two areas: its role in peri-operative liver function monitoring during major hepatic resection and liver transplantation; and its role in critically ill patients on the intensive care unit, where it is used for prediction of mortality, and for assessment of the severity of acute liver failure or that of intra-abdominal hypertension. Although numerous studies have demonstrated that indocyanine green elimination measurements in these patient populations can provide diagnostic or prognostic information to the clinician, 'hard' evidence - i.e. high-quality prospective randomised controlled trials - is lacking, and therefore it is not yet time to give a green light for use of indocyanine green in routine clinical practice.
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Affiliation(s)
- J J Vos
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Angelico M, Nardi A, Romagnoli R, Marianelli T, Corradini SG, Tandoi F, Gavrila C, Salizzoni M, Pinna AD, Cillo U, Gridelli B, De Carlis LG, Colledan M, Gerunda GE, Costa AN, Strazzabosco M. A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study. Dig Liver Dis 2014; 46:340-347. [PMID: 24411484 DOI: 10.1016/j.dld.2013.11.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/07/2013] [Accepted: 11/10/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. METHODS Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. RESULTS A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). CONCLUSION Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability.
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Affiliation(s)
- Mario Angelico
- Liver Unit, Tor Vergata University, Rome, Italy; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy
| | | | - Renato Romagnoli
- Liver Transplant Unit, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Italy; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy.
| | - Tania Marianelli
- Liver Unit, Tor Vergata University, Rome, Italy; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy
| | - Stefano Ginanni Corradini
- Gastroenterology Unit, La Sapienza University, Rome, Italy; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy
| | - Francesco Tandoi
- Liver Transplant Unit, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Italy
| | - Caius Gavrila
- Department of Mathematics, Tor Vergata University, Rome, Italy
| | - Mauro Salizzoni
- Liver Transplant Unit, Azienda Ospedaliera Città della Salute e della Scienza, University of Turin, Italy
| | | | - Umberto Cillo
- Liver Transplant Unit, Università of Padua, Italy; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy
| | | | | | | | | | | | - Mario Strazzabosco
- Digestive Disease Section, University of Milan Bicocca, Milan, Italy; Yale University Liver Centre, New Haven, USA; Italian Association for the Study of the Liver (AISF), Italian National Transplant Centre (CNT) and Italian Liver Transplant Centres, Italy
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Angelico M, Lenci I. Donor–Recipient Matching in HCV-Infected Patients. HEPATITIS C VIRUS AND LIVER TRANSPLANTATION 2014:15-27. [DOI: 10.1007/978-1-4614-8438-7_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Salvalaggio P, Afonso RC, Felga G, Ferraz-Neto BH. A proposal to grade the severity of early allograft dysfunction after liver transplantation. EINSTEIN-SAO PAULO 2013; 11:23-31. [PMID: 23579740 PMCID: PMC4872964 DOI: 10.1590/s1679-45082013000100006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Accepted: 08/25/2012] [Indexed: 12/19/2022] Open
Abstract
Objective: To propose a grading system for early hepatic graft dysfunction. Methods: A retrospective study from a single transplant center. Recipients of liver transplants from deceased donors, transplanted under the MELD system were included. Early graft dysfunction was defined by Olthoff criteria. Multiple cut-off points of post-transplant laboratory tests were used to create a grading system for early graft dysfunction. The primary outcome was 6-months grafts survival. Results: The peak of aminotransferases during the first postoperative week correlated with graft loss. The recipients were divided into mild (aminotransferase peak >2,000IU/mL, but <3,000IU/mL); moderate (aminotransferase peak >3,000IU/mL); and severe (aminotransferase peak >3,000IU/mL + International Normalized Ratio ≥1.6 and/or bilirubin ≥ 10mg/dL in the 7th postoperative day) early allograft dysfunction. Moderate and severe early dysfunctions were independent risk factors for graft loss. Patients with mild early dysfunction presented with graft and patient survival comparable to those without graft dysfunction. However, those with moderate early graft dysfunction showed worse graft survival than those who had no graft dysfunction. Patients with severe early dysfunction had graft and patient survival rates worse than those of any other groups. Conclusion: Early graft dysfunction can be graded by a simple and reliable criteria based on the peak of aminotransferases during the first postoperative week. The severity of the early graft dysfunction is an independent risk factor for allograft loss. Patients with moderate early dysfunction showed worsening of graft survival. Recipients with severe dysfunction had a significantly worse prognosis for graft and patient survival.
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Affiliation(s)
- Paolo Salvalaggio
- Unidade de Transplante de Fígado, Hospital Israelita Albert Einstein, São Paulo, SP, Brasil
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Nachmany I, Dvorchik I, Devera M, Fontes P, Demetris A, Humar A, Marsh JW. A validated model for predicting outcome after liver transplantation: implications on transplanting the extremely sick. Transpl Int 2013; 26:1108-15. [PMID: 24102804 DOI: 10.1111/tri.12171] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2012] [Revised: 10/21/2012] [Accepted: 07/21/2013] [Indexed: 02/06/2023]
Abstract
Given the organ shortage, there is a need to optimize outcome after liver transplantation (LT). We defined posttransplant hospital length of stay > 60 days (LOS > 60) as a surrogate of suboptimal outcome. In the first phase of the study, a 'Study cohort' (SC) of 643 patients was used to identify risk factors and construct a mathematical model to identify recipients with anticipated inferior results. In the second phase, a cohort of 417 patients was used for validation of the model ['Validation Cohort' (VC)]. In the SC, 65 patients (10.1%) had LOS > 60 days. One- and 3-year patient/graft survival rates were 81.9%/76.1% and 73.4%/67.4%, respectively. Patient and graft survival rates of those with LOS > 60 days were inferior (P < 0.0001), while transplant cost was greater [3.42 relative units (RU) vs. 1 RU, P < 0.0001]. In a multivariable analysis, pretransplant dialysis (P < 0.001), mechanical ventilation (P < 0.015), MELD (P < 0.003), and age (P < 0.009) were predictors of LOS > 60 days [ROC curve - 0.75 (95% CI 0.70, 0.81)]. In the VC, 53 patients (12.7%) were expected to have adverse outcome by the model. These patients had longer LOS (P < 0.0001), higher cost (<0.0001), and inferior patient and graft survival (P < 0.007).
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Affiliation(s)
- Ido Nachmany
- Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Pagano D, Grosso G, Vizzini G, Spada M, Cintorino D, Malaguarnera M, Donati M, Mistretta A, Gridelli B, Gruttadauria S. Recipient-donor age matching in liver transplantation: a single-center experience. Transplant Proc 2013; 45:2700-2706. [PMID: 24034027 DOI: 10.1016/j.transproceed.2013.07.039] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The aim of this study was to investigate whether donor age was a predictor of outcomes in liver transplantation, representing an independent risk factor as well as its impact related to recipient age-matching. METHODS We analyzed prospectively collected data from 221 adult liver transplantations performed from January 2006 to September 2009. RESULTS Compared with recipients who received grafts from donors <60 years old, transplantation from older donors was associated with significantly higher rates of graft rejection (9.5% vs 3.5%; P = .05) and worse graft survival (P = .021). When comparing recipient and graft survivals according to age matching, we observed significantly worse values for age-mismatched (P values .029 and .037, respectively) versus age-matched patients. After adjusting for covariates in a multivariate model, age mismatch was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02-15.47; P = .046). CONCLUSIONS The results of this study suggest to that optimized donor allocation takes into account both donor and recipient ages maximize survival of liver-transplanted patients.
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Affiliation(s)
- D Pagano
- Mediterranean Institute for Transplantation and Advanced Specialized Therapies/University of Pittsburgh Medical Center in Italy, Palermo, Italy
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Silberhumer GR, Rahmel A, Karam V, Gonen M, Gyoeri G, Kern B, Adam R, Muehlbacher F, Rogiers X, Burroughs AK, Berlakovich GA. The difficulty in defining extended donor criteria for liver grafts: the Eurotransplant experience. Transpl Int 2013; 26:990-8. [PMID: 23931659 DOI: 10.1111/tri.12156] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 12/14/2012] [Accepted: 06/28/2013] [Indexed: 12/14/2022]
Abstract
Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
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Affiliation(s)
- Gerd R Silberhumer
- Department of Transplant Surgery, Medical University Vienna, Vienna, Austria
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op den Dries S, Karimian N, Sutton ME, Westerkamp AC, Nijsten MWN, Gouw ASH, Wiersema-Buist J, Lisman T, Leuvenink HGD, Porte RJ. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers. Am J Transplant 2013; 13:1327-35. [PMID: 23463950 DOI: 10.1111/ajt.12187] [Citation(s) in RCA: 226] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 01/07/2013] [Accepted: 01/10/2013] [Indexed: 01/25/2023]
Abstract
In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion may reduce preservation injury, improve graft viability and potentially allows ex vivo assessment of graft viability before transplantation. We have studied the feasibility of normothermic machine perfusion in four discarded human donor livers. Normothermic machine perfusion consisted of pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion for 6 h. Two hollow fiber membrane oxygenators provided oxygenation of the perfusion fluid. Biochemical markers in the perfusion fluid reflected minimal hepatic injury and improving function. Lactate levels decreased to normal values, reflecting active metabolism by the liver (mean lactate 10.0 ± 2.3 mmol/L at 30 min to 2.3 ± 1.2 mmol/L at 6 h). Bile production was observed throughout the 6 h perfusion period (mean rate 8.16 ± 0.65 g/h after the first hour). Histological examination before and after 6 h of perfusion showed well-preserved liver morphology without signs of additional hepatocellular ischemia, biliary injury or sinusoidal damage. In conclusion, this study shows that normothermic machine perfusion of human donor livers is technically feasible. It allows assessment of graft viability before transplantation, which opens new avenues for organ selection, therapeutic interventions and preconditioning.
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Affiliation(s)
- S op den Dries
- Section of Hepatobiliary Surgery and Liver Transplantation, Department of SurgeryUniversity Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Angelico M, Nardi A, Marianelli T, Caccamo L, Romagnoli R, Tisone G, Pinna AD, Avolio AW, Fagiuoli S, Burra P, Strazzabosco M, Costa AN. Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: evidence from the Liver Match cohort study. J Hepatol 2013. [PMID: 23201239 DOI: 10.1016/j.jhep.2012.11.025] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. METHODS We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. RESULTS 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325). CONCLUSIONS HBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.
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Wenger U, Neff TA, Oberkofler CE, Zimmermann M, Stehberger PA, Scherrer M, Schuepbach RA, Cottini SR, Steiger P, Béchir M. The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study. BMC Nephrol 2013; 14:37. [PMID: 23409777 PMCID: PMC3582487 DOI: 10.1186/1471-2369-14-37] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2012] [Accepted: 02/13/2013] [Indexed: 12/24/2022] Open
Abstract
Background Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. Methods In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. Results There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups. The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively). The hazard ratio in this group was 9.6 (CI 3.2-28.6, p=.0001). Conclusion This study shows that in liver transplant recipient’s acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.
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Affiliation(s)
- Urs Wenger
- Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH 8091, Switzerland
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Levitsky J, Baker T, Ahya SN, Levin ML, Friedewald J, Gallon L, Ho B, Skaro A, Krupp J, Wang E, Spies SM, Salomon DR, Abecassis MM. Outcomes and native renal recovery following simultaneous liver-kidney transplantation. Am J Transplant 2012; 12:2949-57. [PMID: 22759344 DOI: 10.1111/j.1600-6143.2012.04182.x] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
With the increase in patients having impaired renal function at liver transplant due to MELD, accurate predictors of posttransplant native renal recovery are needed to select candidates for simultaneous liver-kidney transplantation (SLK). Current UNOS guidelines rely on specific clinical criteria for SLK allocation. To examine these guidelines and other variables predicting nonrecovery, we analyzed 155 SLK recipients, focusing on a subset (n = 78) that had post-SLK native GFR (nGFR) determined by radionuclide renal scans. The 77 patients not having renal scans received a higher number of extended criteria donor organs and had worse posttransplant survival. Of the 78 renal scan patients, 31 met and 47 did not meet pre-SLK UNOS criteria. The UNOS criteria were more predictive than our institutional criteria for all nGFR recovery thresholds (20-40 mL/min), although at the most conservative cut-off (nGFR ≤ 20) it had low sensitivity (55.3%), specificity (75%), PPV (67.6%) and NPV (63.8%) for predicting post-SLK nonrecovery. On multivariate analysis, the only predictor of native renal nonrecovery (nGFR ≤ 20) was abnormal pre-SLK renal imaging (OR 3.85, CI 1.22-12.5). Our data support the need to refine SLK selection utilizing more definitive biomarkers and predictors of native renal recovery than current clinical criteria.
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Affiliation(s)
- J Levitsky
- Comprehensive Transplant Center, Northwestern University, Chicago, IL, USA.
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Goldaracena N, Quiñonez E, Méndez P, Anders M, Orozco Ganem F, Mastai R, McCormack L. Extremely Marginal Liver Grafts From Deceased Donors Have Outcome Similar to Ideal Grafts. Transplant Proc 2012; 44:2219-22. [DOI: 10.1016/j.transproceed.2012.07.113] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Bruzzone P. A Preliminary European Study on Extended-Criteria Liver Donation and Transplant Recipient Consent. Transplant Proc 2012; 44:1857-8. [DOI: 10.1016/j.transproceed.2012.05.065] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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49
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Joint Impact of Donor and Recipient Parameters on the Outcome of Liver Transplantation in Germany. Transplantation 2011; 92:1378-84. [DOI: 10.1097/tp.0b013e318236cd2f] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Rodrigue JR, Hanto DW, Curry MP. Patients' willingness to accept expanded criteria donor liver transplantation. Am J Transplant 2011; 11:1705-11. [PMID: 21672150 DOI: 10.1111/j.1600-6143.2011.03592.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Utilization of livers from expanded criteria donors (ECD) is one strategy to overcome the severe organ shortage. The decision to utilize an ECD liver is complex and fraught with uncertainty for both providers and patients. We assessed patients' willingness to accept ECD liver transplantation (LTx) and acceptable 1-year mortality risk. One hundred eight patients listed for LTx were asked to rate their willingness to accept ECD LTx and the associated 1-year mortality risk they were willing to accept. Also, patients completed the SF-36v2 and sociodemographic and health information was gathered from their medical records. Patients reported significantly higher willingness to accept standard criteria donor (SCD) versus ECD LTx (t = 13.8, p < 0.001), with more than one-third of patients reporting low willingness to accept ECD LTx. Relative to our center's 10% SCD LTx 1-year mortality rate, most patients (71%) were willing to accept moderately or substantially higher 1-year mortality risk for ECD LTx. In multivariable analyses, higher lab MELD score and white race were significant independent predictors of both ECD willingness and ECD increased mortality risk acceptability. Findings highlight the importance of assessing patients' willingness to pursue ECD LTx and the relative mortality risks they are willing to accept.
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Affiliation(s)
- J R Rodrigue
- Center for Transplant Outcomes and Quality Improvement, The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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