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Okumura K, Dhand A, Hasjim BJ, Misawa R, Sogawa H, Veillette G, Nishida S. Liver transplant practices in the era of normothermic machine perfusion in the United States. World J Transplant 2025; 15:100427. [DOI: 10.5500/wjt.v15.i2.100427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 12/05/2024] [Accepted: 12/27/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND Normothermic liver machine perfusion (NMP) is a novel technology used to preserve and evaluate the function of liver allografts.
AIM To assess NMP utilization in liver transplant (LT) practices.
METHODS All adult deceased-donor LT recipients between January 2021 and September 2023 in the United States were analyzed. Outcomes including discard rates, survival, preservation time and timing of surgery were compared between two groups: NMP vs non-NMP.
RESULTS Between 2021 and 2023, NMP was utilized in 1493 (6.3%) of all LTs in the United States. Compared to non-NMP group, NMP group had lower allograft discard rate (6.5% vs 10%, P < 0.001), older recipients’ age (median: 47 vs 42 years, P < 0.001), and higher utilization of donors from donation after circulatory death (DCD) (55% vs 11%, P < 0.001). NMP group also had longer distances between recipient and donor hospitals (median: 156 vs 138 miles, P < 0.001), longer preservation time (median: 12.2 vs 5.8 hours, P < 0.001), and more daytime reperfusion (74% vs 55%, P < 0.001). Post-transplant survival outcomes were comparable between the two groups. In a subgroup analysis of NMP, recipients in the long preservation time (≥ 8 hours) group had higher daytime reperfusion (78% vs 55%, P < 0.001) and similar post-transplant survival when compared to the short preservation time (< 8 hours) group.
CONCLUSION The utilization of NMP is associated with lower discard rates and increased DCD organs for LT. NMP allows for prolonging the preservation time and increased occurrence of daytime LT, without any impact on the survival outcomes.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Bima J Hasjim
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92697, United States
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
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Dingfelder J, Kollmann D, Rauter L, Pereyra D, Kacar S, Weijler AM, Saffarian Zadeh T, Tortopis C, Silberhumer G, Salat A, Soliman T, Berlakovich G, Györi GP. Validation of mitochondrial FMN as a predictor for early allograft dysfunction and patient survival measured during hypothermic oxygenated perfusion. Liver Transpl 2025; 31:476-488. [PMID: 39787526 PMCID: PMC11895825 DOI: 10.1097/lvt.0000000000000512] [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: 06/10/2024] [Accepted: 09/21/2024] [Indexed: 01/12/2025]
Abstract
Hypothermic oxygenated machine perfusion (HOPE) preconditions liver grafts before transplantation. While beneficial effects on patient outcomes were demonstrated, biomarkers for viability assessment during HOPE are scarce and lack validation. This study aims to validate the predictive potential of perfusate flavin mononucleotide (FMN) during HOPE to enable the implementation of FMN-based assessment into clinical routine and to identify safe organ acceptance thresholds. FMN was measured in perfusate samples of 50 liver grafts at multiple time points. After transplantation, patients were followed up for development of early allograft dysfunction (EAD), transplantation, and 1-year survival. FMN concentrations were significantly higher for grafts that developed EAD at 5 and 60 minutes into HOPE ( p = 0.008, p = 0.026). The strongest predictive potential of FMN for EAD was observed at 5 minutes of HOPE with an AUC of 0.744. Similarly, 5-minute FMN was predictive for 1-year mortality ( p < 0.001), reaching a remarkable AUC of 0.890. Cutoffs for prediction of EAD (10.6 ng/mL) and early mortality (23.5 ng/mL) were determined and allowed risk stratification of grafts. Particularly, patients receiving low-risk grafts developed EAD in 9% of cases, while all patients survived the first postoperative year. In contrast, high-risk organs developed an incidence of EAD at 62%, accompanied by the necessity of retransplantation in 38% of cases. One-year mortality in the high-risk cohort was 62%. Evaluation of FMN as early as 5 minutes during HOPE allows for risk stratification of liver grafts. Low-risk grafts, according to FMN, display a negligible risk for patients. Yet, high-risk grafts are associated with increased risk for EAD, transplantation, and early mortality and should not be used for transplantation without further assessment.
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Affiliation(s)
- Jule Dingfelder
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Dagmar Kollmann
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Laurin Rauter
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - David Pereyra
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Sertac Kacar
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Anna M. Weijler
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Tina Saffarian Zadeh
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Chiara Tortopis
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Gerd Silberhumer
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Andreas Salat
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Thomas Soliman
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Gabriela Berlakovich
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
| | - Georg P. Györi
- Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria
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Vidgren M, Delorme C, Oniscu GC. Challenges and opportunities in organ donation after circulatory death. J Intern Med 2025; 297:124-140. [PMID: 39829342 PMCID: PMC11771584 DOI: 10.1111/joim.20051] [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] [Indexed: 01/22/2025]
Abstract
In recent years, there has been resurgence in donation after circulatory death (DCD). Despite that, the number of organs transplanted from these donors remains low due to concerns about their function and a lack of an objective assessment at the time of donation. This overview examines the current DCD practices and the classification modifications to accommodate regional perspectives. Several risk factors underscore the reluctance to accept DCD organs, and we discuss the modern strategies to mitigate them. The advent of machine perfusion technology has revolutionized the field of DCD transplantation, leading to improved outcomes and better organ usage. With many strategies at our disposal, there is an urgent need for comparative trials to determine the optimal use of perfusion technologies for each donated organ type. Additional progress in defining therapeutic strategies to repair the damage sustained during the dying process should further improve DCD organ utilization and outcomes. However, there remains wide variability in access to DCD donation and transplantation, and organizational efforts should be doubled up with consensus on key ethical issues that still surround DCD donation in the era of machine perfusion.
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Affiliation(s)
- Mathias Vidgren
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
| | - Capucine Delorme
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
| | - Gabriel C. Oniscu
- Division of Transplantation SurgeryCLINTEC, Karolinska InstitutetStockholmSweden
- Department of Transplantation SurgeryKarolinska Universitetssjukhuset HuddingeHuddingeSweden
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4
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Li Y, Liu X, Zhang C, Tao R, Pan B, Liu W, Jiang D, Hu F, Xu Z, Tan D, Ou Y, Li X, You Y, Zhang L. A Brief Model Evaluated Outcomes After Liver Transplantation Based on the Matching of Donor Graft and Recipient. Clin Transl Gastroenterol 2025; 16:e00761. [PMID: 39166764 PMCID: PMC11756882 DOI: 10.14309/ctg.0000000000000761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 07/31/2024] [Indexed: 08/23/2024] Open
Abstract
INTRODUCTION A precise model for predicting outcomes is needed to guide perioperative management. With the development of the liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes. METHODS The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver-operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications. RESULTS Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) ( P = 0.012) and Model for End-Stage Liver Disease (MELD) ( P = 0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06 < grade 2 ≤ 1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications. DISCUSSION The model integrating variables from graft donors and recipients made the prediction more accurate and available. CMI provided new insight into outcome evaluation and risk factor management of LT.
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Affiliation(s)
- Yuancheng Li
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xingchao Liu
- Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Chengcheng Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ran Tao
- Department of Organ Transplantation, Liaocheng People's Hospital, Liaocheng, China
| | - Bi Pan
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wei Liu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Di Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Hu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Zeliang Xu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Dehong Tan
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yanjiao Ou
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xun Li
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yuemei You
- Department of Surgery and Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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Messner F, Sardu C, Petruzzo P. Grasping time - longevity of vascularized composite allografts. Curr Opin Organ Transplant 2024; 29:376-381. [PMID: 39470048 DOI: 10.1097/mot.0000000000001177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2024]
Abstract
PURPOSE OF REVIEW Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes. RECENT FINDINGS Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field. SUMMARY Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.
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Affiliation(s)
| | - Claudia Sardu
- Department of Public Health and Epidemiology, University of Cagliari, Cagliari, Italy
| | - Palmina Petruzzo
- Department of Transplantation, Hopital Edouard Herriot, HCL, Lyon, France
- Department of Surgery, University of Cagliari, Cagliari, Italy
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Khan MQ, Watt KD, Teasdale C. Development of posttransplant diabetes mellitus in US recipients of liver transplant is influenced by OPTN region. Liver Transpl 2024:01445473-990000000-00487. [PMID: 39724669 DOI: 10.1097/lvt.0000000000000508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 09/24/2024] [Indexed: 12/28/2024]
Abstract
Posttransplant diabetes mellitus (PTDM) is associated with significant morbidity and mortality in liver transplant recipients (LTRs). We used the Organ Procurement and Transplantation Network (OPTN) database to compare the incidence of developing PTDM across the United States and develop a risk prediction model for new-onset PTDM using OPTN region as well as donor-related, recipient-related, and transplant-related factors. All US adult, primary, deceased donor, LTRs between January 1, 2007, and December 31, 2016, with no prior history of diabetes noted, were identified. Kaplan-Meier estimators were used to calculate the cumulative incidence of PTDM, stratified by OPTN region. Multivariable Cox proportional hazards models were fitted to estimate hazards of PTDM in each OPTN region and build a risk prediction model, through backward selection. Cumulative incidence of PTDM at 1 year, 3 years, and 5 years after transplant was 12.0%, 16.1%, and 18.9%, respectively. Region 3, followed by regions 8, 2, and 9, had the highest adjusted hazards of developing PTDM. Inclusion of OPTN region in a risk prediction model for PTDM in LTRs (including recipient age, sex, race, education, insurance coverage, body mass index, primary liver disease, cold ischemia time, and donor history of diabetes) modestly improved performance (C-statistic = 0.60). In patients without pre-existing, confirmed diabetes mellitus, the incidence of PTDM in LTRs varied across OPTN regions, with the highest hazards in region 3, followed by regions 8, 2, and 9. The performance of a novel risk prediction model for PTDM in LTRs has improved performance with the inclusion of the OPTN region. Vigilance is recommended to centers in high-risk regions to identify PTDM and mitigate its development.
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Affiliation(s)
- Mohammad Qasim Khan
- Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
| | - Kymberly D Watt
- Division of Gastroenterology & Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Chloe Teasdale
- Department of Epidemiology and Biostatistics, CUNY Graduate School of Public Health and Health Policy, New York, New York, USA
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7
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Anilir E, Sönmez Topçu F, Şahin E, Oral A, Ayyildiz Civan H, Orhan Poyrazoğlu K, Dirican A, Ünal B. Effects of Peroperative Cold Ischemia Time and Anhepatic Phase in Adult Living Donor Liver Transplant Recipients: Operation Time That is Not Affected by the Anhepatic Phase But is Prolonged by Cold Ischemia Time. Transplant Proc 2024; 56:1374-1377. [PMID: 39003204 DOI: 10.1016/j.transproceed.2024.02.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 01/25/2024] [Accepted: 02/16/2024] [Indexed: 07/15/2024]
Abstract
OBJECTIVE It was aimed to examine the overall role of cold ischemia time and anhepatic phase durations in terms of peroperative blood transfusion needs, hospital stay conditions and postoperative charges, and survival in recipients. MATERIAL AND METHODS One hundred forty-eight adult living donor liver transplant recipients (18 years and older) were included in the study. Whether the anhepatic phase and cold ischemia duration have an effect on the rates of surgery time, blood product transfusion, total hospital and intensive care unit stay, postoperative biliary complications, hepatic vein thrombosis, portal vein thrombosis, early postoperative bleeding, sepsis, and primary graft dysfunction. Was analyzed statistically. In addition, the effect of the anhepatic phase and cold ischemia time on graft survival was statistically examined by creating an average of the patient follow-up period. RESULTS It was observed that the operation time increased statistically as the cold ischemia time increased (P = .000). No statistically significant relationship was found between other findings and cold ischemia time and anhepatic phase. CONCLUSION Prolonged surgery time due to increased cold ischemia time may be an important finding in terms of peroperative and postoperative results of the graft.
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Affiliation(s)
- Ender Anilir
- Organ Transplantation Center, Biruni University Hospital, İstanbul, Türkiye.
| | - Feyza Sönmez Topçu
- Radiology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Emrah Şahin
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Alihan Oral
- İnternal Medicine Department, Fenerbahce University, Biruni University, İstanbul, Türkiye
| | - Hasret Ayyildiz Civan
- Pediatric Gastroenterology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Kürşat Orhan Poyrazoğlu
- Gastroenterology Department, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Abuzer Dirican
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
| | - Bülent Ünal
- Organ Transplantation Center, İstanbul Aydın University Medical Park Florya Hospital, İstanbul, Türkiye
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8
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Cesaretti M, Izzo A, Pellegrino RA, Galli A, Mavrothalassitis O. Cold ischemia time in liver transplantation: An overview. World J Hepatol 2024; 16:883-890. [PMID: 38948435 PMCID: PMC11212655 DOI: 10.4254/wjh.v16.i6.883] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/26/2024] [Accepted: 05/20/2024] [Indexed: 06/20/2024] Open
Abstract
The standard approach to organ preservation in liver transplantation is by static cold storage and the time between the cross-clamping of a graft in a donor and its reperfusion in the recipient is defined as cold ischemia time (CIT). This simple definition reveals a multifactorial time frame that depends on donor hepatectomy time, transit time, and recipient surgery time, and is one of the most important donor-related risk factors which may influence the graft and recipient's survival. Recently, the growing demand for the use of marginal liver grafts has prompted scientific exploration to analyze ischemia time factors and develop different organ preservation strategies. This review details the CIT definition and analyzes its different factors. It also explores the most recent strategies developed to implement each timestamp of CIT and to protect the graft from ischemic injury.
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Affiliation(s)
- Manuela Cesaretti
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari 09122, Italy
- Department of Nanophysic, Istituto Italiano di Tecnologia, Genova 16163, Italy.
| | - Alessandro Izzo
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari 09122, Italy
| | | | - Alessandro Galli
- Department of Critical Care Medicine and Anesthesia, ASST Papa Giovanni XXIII, Bergamo 24100, Italy
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, United States
| | - Orestes Mavrothalassitis
- Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA 94143, United States
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Li Z, Sng YP, Chen CL, Lin CC, Wang SH, Yong CC. A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation. Hepatobiliary Surg Nutr 2024; 13:425-443. [PMID: 38911194 PMCID: PMC11190508 DOI: 10.21037/hbsn-23-178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 07/26/2023] [Indexed: 06/25/2024]
Abstract
Background Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. Methods This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Results Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Conclusions Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.
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Affiliation(s)
- Zhihao Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Yi Ping Sng
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Shih-Ho Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
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10
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Mathis S, Putzer G, Gasteiger L, Eschertzhuber S, Schneeberger S, Cardini B, Hell T, Martini J. Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis. Transplant Direct 2024; 10:e1628. [PMID: 38757047 PMCID: PMC11098234 DOI: 10.1097/txd.0000000000001628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/26/2024] [Accepted: 02/15/2024] [Indexed: 05/18/2024] Open
Abstract
Background Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Methods Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. Results After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. Conclusions This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.
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Affiliation(s)
- Simon Mathis
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Gabriel Putzer
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Lukas Gasteiger
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Stephan Eschertzhuber
- Department of Anaesthesiology and Intensive Care Medicine, Hospital Hall in Tirol, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Judith Martini
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
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Custodio G, Massutti AM, Caramori A, Pereira TG, Dalazen A, Scheidt G, Thomazini L, Leitão CB, Rech TH. Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study. World J Transplant 2024; 14:89702. [PMID: 38576765 PMCID: PMC10989463 DOI: 10.5500/wjt.v14.i1.89702] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/13/2023] [Accepted: 01/12/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation. AIM To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients, mainly early allograft dysfunction. METHODS This multicenter retrospective study included brain-dead donors and adult liver graft recipients. Donor-recipient matching was obtained through a crossover list. Clinical and laboratory data were recorded for both donors and recipients. Donor hepatectomy, cold ischemia, and warm ischemia times were recorded. Primary outcome was early allograft dysfunction. Secondary outcomes included need for retransplantation, length of intensive care unit and hospital stay, and patient and graft survival at 12 months. RESULTS From January 2019 to December 2021, a total of 243 patients underwent a liver transplant from a brain-dead donor. Of these, 57 (25%) developed early allograft dysfunction. The median donor hepatectomy time was 29 (23-40) min. Patients with early allograft dysfunction had a median hepatectomy time of 25 (22-38) min, whereas those without it had a median time of 30 (24-40) min (P = 0.126). CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction, graft survival, or patient survival following liver transplantation.
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Affiliation(s)
- Geisiane Custodio
- Department of Intensive Care Unit, Hospital Santa Isabel, Blumenau-Santa Catarina CEP-89010906, Brazil
| | - Andrew Maykon Massutti
- Transplant Division, Hospital Santa Isabel, Blumenau-Santa Catarina CEP-89010906, Brazil
| | - Aline Caramori
- Transplant Division, Hospital Santa Isabel, Blumenau-Santa Catarina CEP-89010906, Brazil
| | | | - Augusto Dalazen
- Transplant Division, Hospital Santa Isabel, Blumenau-Santa Catarina CEP-89010906, Brazil
| | - Gabriela Scheidt
- School of Medicine, Universidade Regional de Blumenau (FURB), Blumenau-Santa Catarina CEP-89010906, Brazil
| | - Ludmilla Thomazini
- School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil
| | - Cristiane Bauermann Leitão
- Departement of Endocrinology, Hospital de Clínicas de Porto Alegre/Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
| | - Tatiana Helena Rech
- Department of Internal Medicine, Hospital de Clínicas de Porto Alegre, Division of Intensive Care Medicine, Porto Alegre 90035-903, Brazil
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12
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Ho CT, Vu VQ, Dang KK, Pham HM, Le VT, Le TH, Nguyen HNA, Ho VL, Vu NT, Nguyen CT. Effect of Donors' Biliary Variation on Postoperative Biliary Complications in Living Donor Liver Transplantation: A Single-Center Observational Study in Vietnam. Transplant Proc 2024; 56:322-329. [PMID: 38402061 DOI: 10.1016/j.transproceed.2023.12.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 11/26/2023] [Accepted: 12/28/2023] [Indexed: 02/26/2024]
Abstract
BACKGROUND Our study aims to evaluate the biliary anatomy variation according to the Varotti classification and its correlation with surgical outcomes for both donors and recipients undergoing living donor liver transplants (LDLTs). METHODS A retrospective analysis of 150 LDLT cases performed at a single center in Vietnam with preoperative radiologic evaluations and intraoperative surgical assessments to identify biliary variant anatomy. Postoperative biliary complications were documented and analyzed. Statistical analysis was performed to determine any significant associations between biliary variations and post-transplant outcomes. RESULTS One hundred fifty cases of LDLT at 108 Military Central Hospital from October 2017 to December 2022 were included in our study. Among the donors, the mean age was 30.89 ± 7.23, with male predominance (77.3%). The prevalence of type 1 biliary anatomy was 84.67%. Type 2, 3a, 3b, 4a, and 4b accounted for 5.33%, 2.67%, 5.33%, 0.67%, and 1.33% of cases, respectively. Donors' complications were witnessed in 7 cases (4.67%), and all needed intervention (Clavien-Dindo grade 3). Biliary complications were found in 36 (24.0%) recipients, with 22 (14.67%) cases of biliary stenosis and 16 (10.67%) cases of biliary leak, including 2 cases encountering both complications. Age, gender, graft type, preoperative liver function, biliary variant anatomy, number of graft orifices, Model for End-Stage Liver Disease score, and blood loss were not significant risk factors for recipients' biliary complications. Cold ischemia time significantly increased the biliary complication rate. CONCLUSIONS This study shows that biliary variant anatomy is common in living liver donors. Such variations should not be a contraindication to liver donation. However, accurate pre- and intraoperative radiologic and surgical evaluations are fundamental for a careful reconstruction plan.
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Affiliation(s)
- Chi Thanh Ho
- Department of Hepato-Biliary-Pancreatic Surgery, Digestive Surgery Center, 103 Military Hospital, Hanoi, 10000, Vietnam
| | - Van Quang Vu
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam.
| | - Kim Khue Dang
- Department of Surgery, VinUniversity, Hanoi 10000, Vietnam
| | - Hoan My Pham
- Department of Surgery, VinUniversity, Hanoi 10000, Vietnam
| | - Van Thanh Le
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
| | - Trung Hieu Le
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
| | - Hoang Ngoc Anh Nguyen
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
| | - Van Linh Ho
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
| | - Ngoc Tuan Vu
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
| | - Cuong Thinh Nguyen
- Department of Hepato-Biliary-Pancreatic Surgery, Institute of Digestive Surgery, 108 Military Central Hospital, Hanoi, 10000, Vietnam
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13
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Chapman WC, Barbas AS, D'Alessandro AM, Vianna R, Kubal CA, Abt P, Sonnenday C, Barth R, Alvarez-Casas J, Yersiz H, Eckhoff D, Cannon R, Genyk Y, Sher L, Singer A, Feng S, Roll G, Cohen A, Doyle MB, Sudan DL, Al-Adra D, Khan A, Subramanian V, Abraham N, Olthoff K, Tekin A, Berg L, Coussios C, Morris C, Randle L, Friend P, Knechtle SJ. Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial. Ann Surg 2023; 278:e912-e921. [PMID: 37389552 DOI: 10.1097/sla.0000000000005934] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2023]
Abstract
OBJECTIVE To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.
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Affiliation(s)
- William C Chapman
- Department of Surgery, School of Medicine, Washington University, St. Louis
| | | | | | - Rodrigo Vianna
- Department of Surgery, University of Miami School of Medicine
| | | | - Peter Abt
- Department of Surgery, University of Pennsylvania School of Medicine
| | | | - Rolf Barth
- Department of Surgery, University of Chicago School of Medicine
| | | | - Hasan Yersiz
- Department of Surgery, David Geffen School of Medicine at UCLA
| | - Devin Eckhoff
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School
| | - Robert Cannon
- Department of Surgery, University of Alabama School of Medicine
| | - Yuri Genyk
- Department of Surgery, Keck School of Medicine of USC
| | - Linda Sher
- Department of Surgery, Keck School of Medicine of USC
| | | | - Sandy Feng
- Department of Surgery, UCSF School of Medicine
| | | | - Ari Cohen
- Department of Surgery, Ochsner Clinic
| | - Maria B Doyle
- Department of Surgery, School of Medicine, Washington University, St. Louis
| | - Debra L Sudan
- Department of Surgery, Duke University School of Medicine
| | - David Al-Adra
- Department of Surgery, School of Medicine, University of Wisconsin, Madison
| | - Adeel Khan
- Department of Surgery, School of Medicine, Washington University, St. Louis
| | | | - Nader Abraham
- Department of Surgery, Duke University School of Medicine
| | - Kim Olthoff
- Department of Surgery, University of Pennsylvania School of Medicine
| | - Akin Tekin
- Department of Surgery, University of Miami School of Medicine
| | - Lynn Berg
- Department of Surgery, School of Medicine, University of Wisconsin, Madison
| | | | - Chris Morris
- Department of Surgery, Ochsner Medical Center, New Orleans, LA
| | - Lucy Randle
- Department of Surgery, Ochsner Medical Center, New Orleans, LA
| | - Peter Friend
- Department of Surgery, Ochsner Medical Center, New Orleans, LA
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14
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Moore HB, Saben J, Rodriguez I, Bababekov YJ, Pomposelli JJ, Yoeli D, Ferrell T, Adams MA, Pshak TJ, Kaplan B, Pomfret EA, Nydam TL. Postoperative fibrinolytic resistance is associated with early allograft dysfunction in liver transplantation: A prospective observational study. Liver Transpl 2023; 29:724-734. [PMID: 36749288 PMCID: PMC10293055 DOI: 10.1097/lvt.0000000000000075] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Indexed: 02/08/2023]
Abstract
Perioperative dysfunction of the fibrinolytic system may play a role in adverse outcomes for liver transplant recipients. There is a paucity of data describing the potential impact of the postoperative fibrinolytic system on these outcomes. Our objective was to determine whether fibrinolysis resistance (FR), on postoperative day one (POD-1), was associated with early allograft dysfunction (EAD). We hypothesized that FR, quantified by tissue plasminogen activator thrombelastography, is associated with EAD. Tissue plasminogen activator thrombelastography was performed on POD-1 for 184 liver transplant recipients at a single institution. A tissue plasminogen activator thrombelastography clot lysis at 30 minutes of 0.0% was identified as the cutoff for FR on POD-1. EAD occurred in 32% of the total population. Fifty-nine percent (n=108) of patients were categorized with FR. The rate of EAD was 42% versus 17%, p <0.001 in patients with FR compared with those without, respectively. The association between FR and EAD risk was assessed using multivariable logistic regression after controlling for known risk factors. The odds of having EAD were 2.43 times (95% CI, 1.07-5.50, p =0.03) higher in recipients with FR [model C statistic: 0.76 (95% CI, 0.64-0.83, p <0.001]. An additive effect of receiving a donation after circulatory determination of death graft and having FR in the rate of EAD was observed. Finally, compared with those without FR, recipients with FR had significantly shorter graft survival time ( p =0.03). In conclusion, FR on POD-1 is associated with EAD and decreased graft survival time. Postoperative viscoelastic testing may provide clinical utility in identifying patients at risk for developing EAD, especially for recipients receiving donation after circulatory determination of death grafts.
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Affiliation(s)
- Hunter B Moore
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
- Department of Surgery, Children’s Hospital Colorado, Aurora, Colorado
| | - Jessica Saben
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Ivan Rodriguez
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Yanik J Bababekov
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - James J Pomposelli
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Dor Yoeli
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Tanner Ferrell
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Megan A Adams
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
- Department of Surgery, Children’s Hospital Colorado, Aurora, Colorado
| | - Thomas J Pshak
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Bruce Kaplan
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Elizabeth A Pomfret
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
| | - Trevor L Nydam
- Departments of Surgery, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado
- Colorado Center for Transplantation Care, Research and Education (CCTCARE), Aurora, Colorado
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15
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Yokoyama APH, Kutner JM, de Moraes Mazetto Fonseca B, Mesquita GLTV, Sakashita AM, Dos Santos APR, Nakazawa CY, de Almeida MD, de Andrade Orsi FL. Neutrophil extracellular traps (NETs), transfusion requirements and clinical outcomes in orthotopic liver transplantation. J Thromb Thrombolysis 2023:10.1007/s11239-023-02825-7. [PMID: 37227652 DOI: 10.1007/s11239-023-02825-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/25/2023] [Indexed: 05/26/2023]
Abstract
Inflammatory phenomena have a direct impact on the prognosis of orthotopic liver transplantation (OLT). Neutrophil extracellular traps (NETs) contribute to OLT inflammation and hemostasis imbalance in OLT. The association between NETosis, clinical outcomes and transfusion requirements is not determined. To evaluate NETs release during OLT and the effect of NETosis ontransfusion requirements and adverse outcomes in a prospective cohort of patients submitted to OLT. We quantified citrullinated histones (cit-H3) and circulating-free-DNA (cf-DNA) in ninety-three patients submitted to OLT in three periods: pre-transplant, after graft reperfusion and before discharge. NETs markers were compared between these periods using ANOVA test. The association of NETosis and adverse outcomes was evaluated using regression models adjusted for age, sex and corrected MELD. We observed a peak of circulating NETs following reperfusion, evidenced by a 2.4-fold increase in cit-H3 levels in the post-graft reperfusion period (median levels of cit-H3 pre transplant: 0.5 ng/mL, after reperfusion: 1.2 ng/mL and at discharge 0.5 ng/mL, p < 0.0001). We observed an association between increased levels of cit-H3 and in-hospital death (OR = 1.168, 95% CI 1.021-1.336, p = 0.024). No association was found between NETs markers and transfusion requirements. There is a prompt release of NETs after reperfusion that is associated with poorer outcomes and death. Intraoperative NETs release seems to be independent of transfusion requirements. These findings highlight the relevance of inflammation promoted by NETS and its impact on OLT adverse clinical outcomes.
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Affiliation(s)
- Ana Paula Hitomi Yokoyama
- Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, Av Albert Einstein, 627-3o Andar, São Paulo, SP, 05652-000, Brazil.
- Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
| | - Jose Mauro Kutner
- Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, Av Albert Einstein, 627-3o Andar, São Paulo, SP, 05652-000, Brazil
| | | | | | - Araci Massami Sakashita
- Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, Av Albert Einstein, 627-3o Andar, São Paulo, SP, 05652-000, Brazil
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16
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Eden J, Sousa Da Silva R, Cortes-Cerisuelo M, Croome K, De Carlis R, Hessheimer AJ, Muller X, de Goeij F, Banz V, Magini G, Compagnon P, Elmer A, Lauterio A, Panconesi R, Widmer J, Dondossola D, Muiesan P, Monbaliu D, de Rosner van Rosmalen M, Detry O, Fondevila C, Jochmans I, Pirenne J, Immer F, Oniscu GC, de Jonge J, Lesurtel M, De Carlis LG, Taner CB, Heaton N, Schlegel A, Dutkowski P. Utilization of livers donated after circulatory death for transplantation - An international comparison. J Hepatol 2023; 78:1007-1016. [PMID: 36740047 DOI: 10.1016/j.jhep.2023.01.025] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/21/2023] [Accepted: 01/27/2023] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.
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Affiliation(s)
- Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Richard Sousa Da Silva
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | | | - Kristopher Croome
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Amelia J Hessheimer
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Xavier Muller
- Department of Digestive Surgery & Liver Transplantation, Croix-Rousse Hospital, University of Lyon I, Lyon, France
| | - Femke de Goeij
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland
| | - Giulia Magini
- Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Philippe Compagnon
- Division of Transplantation, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Andreas Elmer
- Swisstransplant, The Swiss National Foundation for Organ Donation and Transplantation Effingerstrasse 1, 3011 Bern, Switzerland
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - Rebecca Panconesi
- General Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, 10124 Turin, Italy
| | - Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland
| | - Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Paolo Muiesan
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Diethard Monbaliu
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | | | - Olivier Detry
- Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium
| | - Constantino Fondevila
- Hepatopancreatobiliary Surgery & Transplantation, General & Digestive Surgery Service, Hospital Universitario La Paz, IdiPAZ, CIBERehd, Madrid, Spain
| | - Ina Jochmans
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Microbiology, Immunology and Transplantation, Transplantation Research Group, Lab of Abdominal Transplantation, KU Leuven, Belgium; Department of Abdominal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Franz Immer
- Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - Gabriel C Oniscu
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
| | - Jeroen de Jonge
- Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Mickaël Lesurtel
- Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, University of Paris Cité, 100 Bd du Général Leclerc, 92110, Clichy, France
| | - Luciano G De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224 United States
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Centre of Preclinical Research, 20122, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland.
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17
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Avtaar Singh SS, Das De S, Al-Adhami A, Singh R, Hopkins PMA, Curry PA. Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers. World J Transplant 2023; 13:58-85. [PMID: 36968136 PMCID: PMC10037231 DOI: 10.5500/wjt.v13.i3.58] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/11/2022] [Accepted: 02/17/2023] [Indexed: 03/16/2023] Open
Abstract
Lung transplantation is the treatment of choice for patients with end-stage lung disease. Currently, just under 5000 lung transplants are performed worldwide annually. However, a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction. It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. This review aims to provide an in-depth analysis of the epidemiology, pathophysiology, risk factors, outcomes, and future frontiers involved in mitigating primary graft dysfunction. The current diagnostic criteria are examined alongside changes from the previous definition. We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion. Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality, ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.
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Affiliation(s)
- Sanjeet Singh Avtaar Singh
- Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
| | - Sudeep Das De
- Heart and Lung Transplant Unit, Wythenshawe Hospital, Manchester M23 9NJ, United Kingdom
| | - Ahmed Al-Adhami
- Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
- Department of Heart and Lung Transplant, Royal Papworth Hospital, Cambridge CB2 0AY, United Kingdom
| | - Ramesh Singh
- Mechanical Circulatory Support, Inova Health System, Falls Church, VA 22042, United States
| | - Peter MA Hopkins
- Queensland Lung Transplant Service, Prince Charles Hospital, Brisbane, QLD 4032, Australia
| | - Philip Alan Curry
- Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Glasgow G81 4DY, United Kingdom
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Kervella D, Mesnard B, Prudhomme T, Bruneau S, Masset C, Cantarovich D, Blancho G, Branchereau J. Sterile Pancreas Inflammation during Preservation and after Transplantation. Int J Mol Sci 2023; 24:ijms24054636. [PMID: 36902067 PMCID: PMC10003374 DOI: 10.3390/ijms24054636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 02/23/2023] [Accepted: 02/26/2023] [Indexed: 03/04/2023] Open
Abstract
The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response.
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Affiliation(s)
- Delphine Kervella
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Néphrologie et Immunologie Clinique, ITUN, F-44000 Nantes, France
- Correspondence:
| | - Benoît Mesnard
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Service d’Urologie, ITUN, F-44000 Nantes, France
| | - Thomas Prudhomme
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
| | - Sarah Bruneau
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
| | - Christophe Masset
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Néphrologie et Immunologie Clinique, ITUN, F-44000 Nantes, France
| | - Diego Cantarovich
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Néphrologie et Immunologie Clinique, ITUN, F-44000 Nantes, France
| | - Gilles Blancho
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Néphrologie et Immunologie Clinique, ITUN, F-44000 Nantes, France
| | - Julien Branchereau
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- Centre Hospitalier Universitaire de Nantes, Nantes Université, Service d’Urologie, ITUN, F-44000 Nantes, France
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Lozanovski VJ, Adigozalov S, Khajeh E, Ghamarnejad O, Aminizadeh E, Schleicher C, Hackert T, Müller-Stich BP, Merle U, Picardi S, Lund F, Chang DH, Mieth M, Fonouni H, Golriz M, Mehrabi A. Declined Organs for Liver Transplantation: A Right Decision or a Missed Opportunity for Patients with Hepatocellular Carcinoma? Cancers (Basel) 2023; 15:1365. [PMID: 36900157 PMCID: PMC10000136 DOI: 10.3390/cancers15051365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/11/2023] [Accepted: 02/17/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Liver transplantation is the only promising treatment for end-stage liver disease and patients with hepatocellular carcinoma. However, too many organs are rejected for transplantation. METHODS We analyzed the factors involved in organ allocation in our transplant center and reviewed all livers that were declined for transplantation. Reasons for declining organs for transplantation were categorized as major extended donor criteria (maEDC), size mismatch and vascular problems, medical reasons and risk of disease transmission, and other reasons. The fate of the declined organs was analyzed. RESULTS 1086 declined organs were offered 1200 times. A total of 31% of the livers were declined because of maEDC, 35.5% because of size mismatch and vascular problems, 15.8% because of medical reasons and risk of disease transmission, and 20.7% because of other reasons. A total of 40% of the declined organs were allocated and transplanted. A total of 50% of the organs were completely discarded, and significantly more of these grafts had maEDC than grafts that were eventually allocated (37.5% vs. 17.7%, p < 0.001). CONCLUSION Most organs were declined because of poor organ quality. Donor-recipient matching at time of allocation and organ preservation must be improved by allocating maEDC grafts using individualized algorithms that avoid high-risk donor-recipient combinations and unnecessary organ declination.
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Affiliation(s)
- Vladimir J. Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Said Adigozalov
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Christina Schleicher
- German Organ Procurement Organization (Deutsche Stiftung Organtransplantation, DSO), 60594 Frankfurt, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg Eppendorf, 20251 Hamburg, Germany
| | - Beat Peter Müller-Stich
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Uta Merle
- Department of Internal Medicine IV, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Susanne Picardi
- Department of Anesthesiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Frederike Lund
- Department of Anesthesiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - De-Hua Chang
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Department of Radiology, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Hamidreza Fonouni
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Mohammad Golriz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany
- Liver Cancer Center Heidelberg, University Hospital Heidelberg, 69120 Heidelberg, Germany
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20
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Lee YS, Gavzy SJ, Jang J, Kamberi S, Zhang T, Sands L, Scalea JR. Transport-Associated Vibrational Stress Triggers Drug-Reversible Apoptosis and Cardiac Allograft Failure in Mice. IEEE JOURNAL OF TRANSLATIONAL ENGINEERING IN HEALTH AND MEDICINE 2023; 11:145-150. [PMID: 36816099 PMCID: PMC9904449 DOI: 10.1109/jtehm.2023.3239790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/14/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023]
Abstract
Increasingly complex and long-range donor organ allocation routes coupled with implementation of unmanned aerial vehicles (UAVs) have prompted investigations of the conditions affecting organs once packaged for shipment. Our group has previously demonstrated that different modes of organ transport exert unique environmental stressors, in particular vibration. Using a mouse heart transplant model, we demonstrated that vibrational forces exert tangible, cellular effects in the form of cardiomyocyte apoptosis and cytoskeletal derangement. Functionally, these changes translated into accelerated allograft loss. Notably, administration of an apoptosis inhibitor, Z-VAD-FMK, helped to ameliorate the detrimental cellular and functional effects of mechanical vibration in a dose-dependent manner. These findings constitute one of the first reports of the negative impact of transit environment on transplant outcomes, a contributing mechanism underpinning this effect, and a potential agent to prophylax against this process. Given current limitations in measuring donor organ transit environments in situ, further study is required to better characterize the impact of transport environment and to potentially improve the care of donor organs during shipment. Clinical and Translational Impact Statement: We show that apoptosis inhibitor, Z-VAD-FMK, ameliorated transport-related vibrational stress in murine heart transplants, which presents a potential therapeutic or preservation solution additive for future use in transporting donor organs.
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Affiliation(s)
- Young S. Lee
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Center for Vascular and Inflammatory DiseasesUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Samuel J. Gavzy
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Center for Vascular and Inflammatory DiseasesUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Jihyun Jang
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Center for Vascular and Inflammatory DiseasesUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Shani Kamberi
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Tianshu Zhang
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Center for Vascular and Inflammatory DiseasesUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Lauren Sands
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
| | - Joseph R. Scalea
- Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Center for Vascular and Inflammatory DiseasesUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Department of Microbiology and ImmunologyUniversity of Maryland School of MedicineBaltimoreMD21201USA
- Department of SurgeryMedical University of South CarolinaCharlestonSC29425USA
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21
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Azizieh Y, Westhaver LP, Badrudin D, Boudreau JE, Gala-Lopez BL. Changing liver utilization and discard rates in clinical transplantation in the ex-vivo machine preservation era. FRONTIERS IN MEDICAL TECHNOLOGY 2023; 5:1079003. [PMID: 36908294 PMCID: PMC9996101 DOI: 10.3389/fmedt.2023.1079003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 01/30/2023] [Indexed: 02/25/2023] Open
Abstract
Liver transplantation is a well-established treatment for many with end-stage liver disease. Unfortunately, the increasing organ demand has surpassed the donor supply, and approximately 30% of patients die while waiting for a suitable liver. Clinicians are often forced to consider livers of inferior quality to increase organ donation rates, but ultimately, many of those organs end up being discarded. Extensive testing in experimental animals and humans has shown that ex-vivo machine preservation allows for a more objective characterization of the graft outside the body, with particular benefit for suboptimal organs. This review focuses on the history of the implementation of ex-vivo liver machine preservation and how its enactment may modify our current concept of organ acceptability. We provide a brief overview of the major drivers of organ discard (age, ischemia time, steatosis, etc.) and how this technology may ultimately revert such a trend. We also discuss future directions for this technology, including the identification of new markers of injury and repair and the opportunity for other ex-vivo regenerative therapies. Finally, we discuss the value of this technology, considering current and future donor characteristics in the North American population that may result in a significant organ discard.
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Affiliation(s)
- Yara Azizieh
- Department of Pathology, Dalhousie University, Halifax, NS, Canada
| | | | - David Badrudin
- Department of Surgery, Université de Montréal, Montréal, QC, Canada
| | - Jeanette E Boudreau
- Department of Pathology, Dalhousie University, Halifax, NS, Canada.,Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.,Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada
| | - Boris L Gala-Lopez
- Department of Pathology, Dalhousie University, Halifax, NS, Canada.,Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.,Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada.,Department of Surgery, Dalhousie University, Halifax, NS, Canada
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22
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Xu M, Dong C, Sun C, Wang K, Zhang W, Qin H, Han C, Yang Y, Zhang F, Wang Z, Zheng W, Wei X, Gao W, Shen Z. Impact of donor age on short-term outcomes after pediatric split liver transplantation. Front Pediatr 2023; 11:1131629. [PMID: 37114006 PMCID: PMC10126406 DOI: 10.3389/fped.2023.1131629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 03/28/2023] [Indexed: 04/29/2023] Open
Abstract
Background Donor shortage is an important limitation of liver transplantation (LT). Split liver transplantation (SLT) may increase the sources of donors and reduce the problem of organ shortage. However, there are no standard criteria of the selection of SLT donor, especially regarding the donor age. Methods We retrospectively analyzed the clinical data of children who received initial SLT between January 2015 and December 2021. Based on the age of donors, the patients were divided into groups A (1-10 years old; n = 26), B (10-45 years old; n = 87), and C (45-55 years old; n = 27). The short-term (<1 year after SLT) outcomes of the recipients were analyzed. Results A total of 140 patients received SLT from 122 donors. The 1-, 3- and 12-month patient survival rates in group A were 100.0%, and the graft survival rates were 92.3%. The 1-, 3- and 12-month survival rates of patient and graft in group B were 97.7%, 96.6%, and 95.0%, respectively, and in group C were 85.2%, 85.2%, and 81.1%, respectively. The patient survival rate was significantly lower in group C than in groups A and B (p = 0.0082). There was no significant difference in graft survival between the three groups (p = 0.0545). Conclusions Similar results were obtained for pediatric SLT with donors <10 years old and 10-45 years old. Pediatric SLT can be performed with older donors (45-55 years) after strict donor selection and selection of appropriate recipients.
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Affiliation(s)
- Min Xu
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Chong Dong
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Chao Sun
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Kai Wang
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Wei Zhang
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Hong Qin
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Chao Han
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Yang Yang
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Fubo Zhang
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Zhen Wang
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Weiping Zheng
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Xinzhe Wei
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
| | - Wei Gao
- Department of Pediatric Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
- Correspondence: Wei Gao
| | - Zhongyang Shen
- Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China
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23
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Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome and Perioperative Electrolyte Shifts. J Clin Med 2022; 11:jcm11247381. [PMID: 36555997 PMCID: PMC9786550 DOI: 10.3390/jcm11247381] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/08/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (−26%; p = 0.122) and significant reduction of epinephrine consumption (−52%; p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts.
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24
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Pavan-Guimaraes J, Martins PN. Modifying organs with gene therapy and gene modulation in the age of machine perfusion. Curr Opin Organ Transplant 2022; 27:474-480. [PMID: 36102360 DOI: 10.1097/mot.0000000000001007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW This review aims to highlight current advances in gene therapy methods, describing advances in CRISPR-Cas9 gene editing and RNA interference in relevance to liver transplantation, and machine perfusion. RECENT FINDINGS In order to minimize rejection, increase the donor pool of available organs, and minimize the effects of ischemia-reperfusion injury, gene therapy and gene modification strategies are, thus, required in the context of liver transplantation. SUMMARY Gene therapy has been used successfully in a diverse array of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Biological and logistical challenges reduce the rate of successful procedures, increasing the waiting list even more. We explore the exciting future implications of customized gene therapy in livers using machine perfusion, including its potential to create a future in which organs destined for transplant are individualized to maximize both graft and recipient longevity.
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Affiliation(s)
- Juliana Pavan-Guimaraes
- Division of Transplantation, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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25
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Ravaioli M, Germinario G, Dajti G, Sessa M, Vasuri F, Siniscalchi A, Morelli MC, Serenari M, Del Gaudio M, Zanfi C, Odaldi F, Bertuzzo VR, Maroni L, Laurenzi A, Cescon M. Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial. Am J Transplant 2022; 22:2401-2408. [PMID: 35671067 PMCID: PMC9796786 DOI: 10.1111/ajt.17115] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 05/12/2022] [Accepted: 06/03/2022] [Indexed: 01/25/2023]
Abstract
Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.
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Affiliation(s)
- Matteo Ravaioli
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
| | - Giuliana Germinario
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
| | - Gerti Dajti
- Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
| | - Maurizio Sessa
- Department of Drug Design and PharmacologyUniversity of CopenhagenCopenhagenDenmark
| | - Francesco Vasuri
- Department of Specialized, Experimental and Diagnostic Medicine, Pathology UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Antonio Siniscalchi
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Maria Cristina Morelli
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Matteo Serenari
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Massimo Del Gaudio
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Chiara Zanfi
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Federica Odaldi
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Valentina Rosa Bertuzzo
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Lorenzo Maroni
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
| | - Andrea Laurenzi
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Matteo Cescon
- Department of General Surgery and TransplantationIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical Sciences (DIMEC)University of BolognaBolognaItaly
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26
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Muller X, Rossignol G, Mohkam K, Mabrut JY. Novel strategies in liver graft preservation - The French perspective. J Visc Surg 2022; 159:389-398. [PMID: 36109331 DOI: 10.1016/j.jviscsurg.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Given the increasing graft shortage, the transplant community is forced to use so called marginal liver grafts with a higher susceptibility to ischemia-reperfusion injury. This exposes the recipient to a higher risk of graft failure and post-transplant complications. While static cold storage remains the gold standard in low-risk transplant scenarios, dynamic preservation strategies may allow to improve outcomes after transplantation of marginal liver grafts. Two dynamic preservation strategies, end-ischemic hypothermic oxygenated perfusion (HOPE) and continuous normothermic machine perfusion (cNMP), have been evaluated in randomized clinical trials. The results show improved preservation of liver grafts after cNMP and reduction of post-transplant biliary complications after HOPE. In comparison to cNMP, HOPE has the advantage of requiring less logistics and expertise with the possibility to return to default static cold storage. Both strategies allow to assess graft viability prior to transplantation and may thus contribute to optimizing graft selection and reducing discard rates. The use of dynamic preservation is rapidly increasing in France and results from a national randomized trial on the use of HOPE in marginal grafts will soon be available. Future applications should focus on controlled donation after circulatory death liver grafts, split grafts and graft treatment during perfusion. The final aim of dynamic liver graft preservation is to improve post-transplant outcomes, increase the number of transplanted grafts and allow expansion of transplant indications.
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Affiliation(s)
- X Muller
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; ED 340 BMIC, Claude-Bernard Lyon 1 University, 69622 Villeurbanne, France.
| | - G Rossignol
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; ED 340 BMIC, Claude-Bernard Lyon 1 University, 69622 Villeurbanne, France; Department of Pediatric Surgery and Liver Transplantation, Femme-Mère-Enfant University Hospital, Hospices Civils de Lyon, Lyon, France
| | - K Mohkam
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France; Department of Pediatric Surgery and Liver Transplantation, Femme-Mère-Enfant University Hospital, Hospices Civils de Lyon, Lyon, France
| | - J Y Mabrut
- Department of General Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France; The Lyon Cancer Research Centre, Inserm U1052 UMR 5286, Lyon, France
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27
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Decker SO, Krüger A, Wilk H, Uhle F, Bruckner T, Hofer S, Weigand MA, Brenner T, Zivkovic AR. Concurrent Change in Serum Cholinesterase Activity and Midregional-Proadrennomedullin Level Could Predict Patient Outcome following Liver Transplantation. Biomolecules 2022; 12:biom12070989. [PMID: 35883545 PMCID: PMC9312899 DOI: 10.3390/biom12070989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 06/17/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
Background: After liver transplantation (LTX), patients are susceptible to opportunistic infections resulting in reduced outcomes within the early post-transplantation period. The postoperative monitoring of LTX patients has gained much importance in recent years. However, reliable plasmatic markers predicting 90-day outcomes are still lacking. Methods: In the post hoc analysis of a prospective, observational study, butyrylcholinesterase (BChE), mid-regional proadrenomedullin (MR-proADM), as well as conventional inflammatory markers (procalcitonin, C-reactive protein) were evaluated in 93 patients at seven consecutive timepoints within the first 28 days following LTX. Results: Persistently reduced activity of BChE and elevated MR-proADM levels indicated reduced 90-day survival following LTX. Furthermore, reduced BChE and increased MR-proADM activity could indicate early post-transplantation bacterial infections, whereas conventional inflammatory biomarkers showed no diagnostic efficacy within the observation period. Conclusion: Concurrent assessment of BChE and MR-proADM activity might serve as a bedside diagnostic tool for early bacterial infections following liver transplantation. Thus, a combined utilization of the two biomarkers may be a useful tool in the risk evaluation of patients following liver transplantation.
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Affiliation(s)
- Sebastian O. Decker
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
- Correspondence: (S.O.D.); (A.R.Z.); Tel.: +49-(0)62-215636380 (S.O.D.); +49-(0)62-215636843 (A.R.Z.); Fax: +49-(0)62-21565345 (S.O.D. & A.R.Z.)
| | - Albert Krüger
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
| | - Henryk Wilk
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
| | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, Heidelberg University, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany;
| | - Stefan Hofer
- Department of Anesthesiology, Westpfalzklinikum, Kaiserslautern, Hellmut-Hartert-Straße 1, 67655 Kaiserslautern, Germany;
| | - Markus A. Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Aleksandar R. Zivkovic
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120 Heidelberg, Germany; (A.K.); (H.W.); (F.U.); (M.A.W.); (T.B.)
- Correspondence: (S.O.D.); (A.R.Z.); Tel.: +49-(0)62-215636380 (S.O.D.); +49-(0)62-215636843 (A.R.Z.); Fax: +49-(0)62-21565345 (S.O.D. & A.R.Z.)
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28
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Salvage of a Right-extended Split Liver Graft Using Ex Situ Normothermic Machine Perfusion-A New Therapeutic Horizon. Transplantation 2022; 106:e320-e321. [PMID: 35616915 DOI: 10.1097/tp.0000000000004067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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29
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Lozanovski VJ, Unterrainer C, Döhler B, Süsal C, Mehrabi A. Outcome of Extended Right Lobe Liver Transplantations. Liver Transpl 2022; 28:807-818. [PMID: 34806843 DOI: 10.1002/lt.26374] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/23/2021] [Accepted: 11/15/2021] [Indexed: 12/16/2022]
Abstract
Split-liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full-size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression. We also analyzed 612 ERLT and 1224 FSLT 1:2 matched cases to identify factors that affect ERLT outcome. The risk of graft loss was significantly higher following ERLT than following FSLT during the first posttransplantation year in the matched and unmatched collective (hazard ratio [HR], 1.39 and 1.27 and P = 0.01 and 0.006, respectively). Every additional hour of cold ischemia time (CIT) increased the risk of 1-year graft loss by 10% in the ERLT group compared with only 3% in the FSLT group (P = 0.003 and <0.001, respectively). Importantly, the outcome of ERLT and FSLT did not differ significantly if the CIT was below 10 hours (HR, 0.71; P = 0.22). One-year graft and patient survival were lower in high-risk ERLT recipients with a Model for End-Stage Liver Disease (MELD) score of ≥20 (HR, 1.88; P = 0.03 and HR, 2.03; P = 0.02). In the male recipient-male donor combination, ERLT recipients had a higher risk of 1-year graft loss than FSLT recipients (HR, 2.44; P = 0.006). This was probably because of the significantly higher MELD score in ERLT recipients (P = 0.004). ERLT in adults is an adequate alternative to FSLT and offers an elegant solution to the problem of organ shortage as long as the cold storage is less than 10 hours and the recipient's MELD score is <20.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Bernd Döhler
- Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany
| | - Caner Süsal
- Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.,Transplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul, Turkey
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
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30
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Yang M, Khan AR, Lu D, Wei X, Shu W, Xu C, Pan B, Zhou Z, Wang R, Wei Q, Cen B, Cai J, Zheng S, Xu X. Development of a Novel Prognostic Nomogram for High Model for End-Stage Liver Disease Score Recipients Following Deceased Donor Liver Transplantation. Front Med (Lausanne) 2022; 9:772048. [PMID: 35308496 PMCID: PMC8927074 DOI: 10.3389/fmed.2022.772048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/26/2022] [Indexed: 11/24/2022] Open
Abstract
Background A high model of end-stage liver disease (MELD) score (>30) adversely affects outcomes even if patients receive prompt liver transplantation (LT). Therefore, balanced allocation of donor grafts is indispensable to avoid random combinations of donor and recipient risk factors, which often lead to graft or recipient loss. Predictive models aimed at avoiding donor risk factors in high-MELD score recipients are urgently required to obtain satisfactory outcomes. Method Data of patients with MELD score >30 who underwent LT at three transplantation institutes between 2015 and 2018 were retrospectively reviewed. Early allograft dysfunction (EAD), length of intensive care unit (ICU) stay, and graft loss were recorded. Corresponding independent risk factors were analyzed using stepwise multivariable regression analysis. A prediction model of graft loss was developed, and discrimination and calibration were measured. Results After applying the exclusion criteria, 778 patients were enrolled. The incidence of EAD was 34.8% (271/778). Donor graft macrovesicular steatosis, graft-to-recipient weight ratio (GRWR), warm ischemia time (WIT), cold ischemia time (CIT), and ABO blood incompatibility, together with donor serum albumins, were independent predictors of EAD. The incidence of ICU stay over 10 days was 64.7% (503/778). Donor age, recipient's MELD score, Child score, and CIT were independent predictors of ICU stay. The 3-year graft survival rates (GSRs) in the training and validation cohorts were 64.2 and 59.3%, respectively. The independent predictors of graft loss were recipient's Child score, ABO blood type incompatibility, donor serum total bilirubin over 17.1 μmol/L, and cold CIT. A nomogram based on these variables was internally and externally validated and showed good performance (area under the receiver operating characteristic curve = 70.8 and 66.0%, respectively). For a recipient with a high MELD score, the avoidance of ABO blood type incompatibility and CIT ≥6 h would achieve a 3-year GSR of up to 78.4%, whereas the presence of the aforementioned risk factors would decrease the GSR to 35.4%. Conclusion The long-term prognosis of recipients with MELD scores >30 could be greatly improved by avoiding ABO blood type incompatibility and CIT ≥6 h.
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Affiliation(s)
- Mengfan Yang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Di Lu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Wenzhi Shu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Chuanshen Xu
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Binhua Pan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Zhisheng Zhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China
| | - Rui Wang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Beini Cen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Health Commission Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China
| | - Jinzhen Cai
- Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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31
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Junge N, Di Giorgio A, Girard M, Demir Z, Kaminska D, Janowska M, Urbonas V, Varnas D, Maggiore G, Alterio T, Leiskau C, Vondran FWR, Richter N, D’Antiga L, Mikolajczyk R, Pfister ED, Baumann U. Cold Ischemia Time and Graft Fibrosis Are Associated with Autoantibodies after Pediatric Liver Transplantation: A Retrospective Cohort Study of the European Reference Network TransplantChild. CHILDREN (BASEL, SWITZERLAND) 2022; 9:275. [PMID: 35204995 PMCID: PMC8870233 DOI: 10.3390/children9020275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/02/2022] [Accepted: 02/15/2022] [Indexed: 11/25/2022]
Abstract
The reported prevalence of autoantibodies (AAB) (ANA, SMA, LKM, SLA) after pediatric liver transplantation (pLTX) varies considerably from 26-75%, but their clinical impact on outcome is uncertain. We aimed to study the prevalence of AAB after pLTX, their association with donor-, transplant-, and recipient-characteristics, and their relation to outcome. In our multicenter retrospective study, we aimed to clarify conflicting results from earlier studies. Six ERN TransplantChild centers reported data on 242 patients, of whom 61% were AAB positive. Prevalence varied across these centers. Independent of the interval between pLTX and AAB analysis, a one-hour increase in CIT resulted in an odds ratio (OR) of 1.37 (95% CI 1.11-1.69) for SMA positivity and an OR of 1.42 (95%CI 1.18-1.72) for ANA positivity. Steroid-free immunosuppression (IS) versus steroid-including IS (OR 5.28; 95% CI 1.45-19.28) was a risk factor for SMA positivity. Liver enzymes were not associated with ANA or SMA positivity. We did not observe an association of rejection activity index with ANA or SMA. However, the liver fibrosis score in follow-up biopsies was associated with ANA titer and donor age. In conclusion, this first multicenter study on AAB after pLTX showed high AAB prevalence and varied widely between centers. Longer CIT and prednisolone-free-IS were associated with AAB positivity, whereas AAB were not indicative of rejection, but instead were associated with graft fibrosis. The detection of AAB may be a marker of liver fibrosis and may be taken into consideration when indications for liver biopsy and immunosuppressive regimes, or reduction of immunosuppression in long-term follow-up, are being discussed. Prospective immunological profiling of pLTX patients, including AAB, is important to further improve our understanding of transplant immunology and silent graft fibrosis.
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Affiliation(s)
- Norman Junge
- Division for Pediatric Gastroenterology and Hepatology, Department of Peadiatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany; (C.L.); (E.-D.P.); (U.B.)
| | - Angelo Di Giorgio
- Department of Paediatric Hepatology, Gastroenterology and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, 24127 Bergamo, Italy; (A.D.G.); (L.D.)
| | - Muriel Girard
- Hépatologie Pédiatrique–Transplantation Hépatique, Hospital Necker Enfants-Malades, 75015 Paris, France; (M.G.); (Z.D.)
| | - Zeynep Demir
- Hépatologie Pédiatrique–Transplantation Hépatique, Hospital Necker Enfants-Malades, 75015 Paris, France; (M.G.); (Z.D.)
| | - Diana Kaminska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Maria Janowska
- Department of Pediatric Surgery & Organ Transplantation, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Vaidotas Urbonas
- Clinic of Children’s Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (V.U.); (D.V.)
| | - Dominykas Varnas
- Clinic of Children’s Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania; (V.U.); (D.V.)
| | - Giuseppe Maggiore
- Gastrointestinal, Liver, Nutrition Disorders Unit, Liver Transplantation Center, IRCCS Pediatric Hospital Bambino Gesù, 00165 Rome, Italy; (G.M.); (T.A.)
| | - Tommaso Alterio
- Gastrointestinal, Liver, Nutrition Disorders Unit, Liver Transplantation Center, IRCCS Pediatric Hospital Bambino Gesù, 00165 Rome, Italy; (G.M.); (T.A.)
| | - Christoph Leiskau
- Division for Pediatric Gastroenterology and Hepatology, Department of Peadiatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany; (C.L.); (E.-D.P.); (U.B.)
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center Göttingen, Georg August University, 37075 Göttingen, Germany
| | - Florian W. R. Vondran
- Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany; (F.W.R.V.); (N.R.)
| | - Nicolas Richter
- Department of General, Visceral and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany; (F.W.R.V.); (N.R.)
| | - Lorenzo D’Antiga
- Department of Paediatric Hepatology, Gastroenterology and Transplantation, Azienda Ospedaliera Papa Giovanni XXIII, 24127 Bergamo, Italy; (A.D.G.); (L.D.)
| | - Rafael Mikolajczyk
- Institute for Medical Epidemiology, Biometrics and Informatics, Interdisciplinary Center for Health Sciences, Medical Faculty of the Martin Luther University Halle-Wittenberg, 06112 Halle, Germany;
| | - Eva-Doreen Pfister
- Division for Pediatric Gastroenterology and Hepatology, Department of Peadiatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany; (C.L.); (E.-D.P.); (U.B.)
| | - Ulrich Baumann
- Division for Pediatric Gastroenterology and Hepatology, Department of Peadiatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30625 Hannover, Germany; (C.L.); (E.-D.P.); (U.B.)
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32
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Buchwald JE, Martins PN. Designer organs: The future of personalized transplantation. Artif Organs 2022; 46:180-190. [DOI: 10.1111/aor.14151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Julianna E. Buchwald
- Division of Transplantation Department of Surgery University of Massachusetts Chan Medical School Worcester Massachusetts USA
- RNA Therapeutics Institute University of Massachusetts Chan Medical School Worcester Massachusetts USA
| | - Paulo N. Martins
- Division of Transplantation Department of Surgery University of Massachusetts Chan Medical School Worcester Massachusetts USA
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33
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Lozanovski VJ, Ramouz A, Aminizadeh E, Al-Saegh SAH, Khajeh E, Probst H, Picardi S, Rupp C, Chang DH, Probst P, Mehrabi A. Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis. BJS Open 2022; 6:6536147. [PMID: 35211739 PMCID: PMC8874238 DOI: 10.1093/bjsopen/zrab130] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/27/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Heike Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Susanne Picardi
- Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Rupp
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany.,Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - De-Hua Chang
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany.,Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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34
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Young LAJ, Ceresa CDL, Mózes FE, Ellis J, Valkovič L, Colling R, Coussios CC, Friend PJ, Rodgers CT. Noninvasive assessment of steatosis and viability of cold-stored human liver grafts by MRI. Magn Reson Med 2021; 86:3246-3258. [PMID: 34272767 PMCID: PMC7613197 DOI: 10.1002/mrm.28930] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/25/2021] [Accepted: 06/28/2021] [Indexed: 12/02/2022]
Abstract
PURPOSE A shortage of suitable donor livers is driving increased use of higher risk livers for transplantation. However, current biomarkers are not sensitive and specific enough to predict posttransplant liver function. This is limiting the expansion of the donor pool. Therefore, better noninvasive tests are required to determine which livers will function following implantation and hence can be safely transplanted. This study assesses the temperature sensitivity of proton density fat fraction and relaxometry parameters and examines their potential for assessment of liver function ex vivo. METHODS Six ex vivo human livers were scanned during static cold storage following normothermic machine perfusion. Proton density fat fraction, T1 , T2 , and T 2 ∗ were measured repeatedly during cooling on ice. Temperature corrections were derived from these measurements for the parameters that showed significant variation with temperature. RESULTS Strong linear temperature sensitivities were observed for proton density fat fraction (R2 = 0.61, P < .001) and T1 (R2 = 0.78, P < .001). Temperature correction according to a linear model reduced the coefficient of repeatability in these measurements by 41% and 36%, respectively. No temperature dependence was observed in T2 or T 2 ∗ measurements. Comparing livers deemed functional and nonfunctional during normothermic machine perfusion by hemodynamic and biochemical criteria, T1 differed significantly: 516 ± 50 ms for functional versus 679 ± 60 ms for nonfunctional, P = .02. CONCLUSION Temperature correction is essential for robust measurement of proton density fat fraction and T1 in cold-stored human livers. These parameters may provide a noninvasive measure of viability for transplantation.
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Affiliation(s)
- Liam A. J. Young
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Carlo D. L. Ceresa
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Ferenc E. Mózes
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Jane Ellis
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Ladislav Valkovič
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
- Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Richard Colling
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | | | - Peter J. Friend
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Christopher T. Rodgers
- Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
- Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
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35
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Dondossola D, Ravaioli M, Lonati C, Maroni L, Pini A, Accardo C, Germinario G, Antonelli B, Odaldi F, Zanella A, Siniscalchi A, Cescon M, Rossi G. The Role of Ex Situ Hypothermic Oxygenated Machine Perfusion and Cold Preservation Time in Extended Criteria Donation After Circulatory Death and Donation After Brain Death. Liver Transpl 2021; 27:1130-1143. [PMID: 33835695 DOI: 10.1002/lt.26067] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 03/08/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
Hypothermic oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time (WIT) in both donation after brain death (DBD) and donation after circulatory death (DCD). Herein we investigated the protective effects of HOPE in extended criteria donor (ECD) DBD and overextended WIT DCD grafts. The present retrospective case series included 50 livers subjected to end-ischemic HOPE or dual DHOPE in 2 liver transplantation (LT) centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (interquartile range [IQR]). In the study period, 21 grafts were derived from overextended WIT DCD donors (total WIT 54 [IQR, 40-60] minutes and 75% classified as futile), whereas 29 were from ECD DBD. A total of 3 biliary complications and 1 case of ischemia-type biliary lesion were diagnosed. The rate of early allograft dysfunction (EAD) was 20%, and those patients had higher Comprehensive Complication Index scores. Through a changing point analysis, cold preservation time >9 hours was associated with prolonged hospital stays (P = 0.02), higher rates of EAD (P = 0.009), and worst post-LT complications (P = 0.02). Logistic regression analyses indicated a significant relationship between cold preservation time and EAD. No differences were shown in terms of the early post-LT results between LTs performed with DCD and DBD. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of DHOPE obtained satisfactory and promising results using ECD-DBD and overextended DCD grafts. Our findings indicate the need to reduce cold preservation time also in the setting of DHOPE, particularly for grafts showing poor quality.
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Affiliation(s)
- Daniele Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Caterina Lonati
- Center for Preclinical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Lorenzo Maroni
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alessia Pini
- Department of Statistical Sciences, Università Cattolica del Sacro Cuore, Milan, Italy
| | - Caterina Accardo
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuliana Germinario
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Barbara Antonelli
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Federica Odaldi
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alberto Zanella
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.,Department of Anesthesia and Critical Care, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Siniscalchi
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giorgio Rossi
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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36
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Lozanovski VJ, Probst P, Arefidoust A, Ramouz A, Aminizadeh E, Nikdad M, Khajeh E, Ghamarnejad O, Shafiei S, Ali-Hasan-Al-Saegh S, Seide SE, Kalkum E, Nickkholgh A, Czigany Z, Lurje G, Mieth M, Mehrabi A. Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation. Transpl Int 2021; 34:778-800. [PMID: 33728724 DOI: 10.1111/tri.13861] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 02/19/2021] [Accepted: 03/08/2021] [Indexed: 12/12/2022]
Abstract
This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Alireza Arefidoust
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Mohammadsadegh Nikdad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Saeed Shafiei
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan-Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Svenja E Seide
- Institute of Medical Biometry and Informatics (IMBI), University of Heidelberg, Heidelberg, Germany
| | - Eva Kalkum
- The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arash Nickkholgh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Georg Lurje
- Department of Surgery, Charité -Universitätsmedizin Berlin, Berlin, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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37
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Lozanovski VJ, Probst P, Ramouz A, Arefidoust A, Ghamarnejad O, Aminizadeh E, Khajeh E, Mehrabi A. Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified. Transpl Int 2021; 34:622-639. [PMID: 33471399 DOI: 10.1111/tri.13824] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/10/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10 594 articles. After exclusion, 22 studies (n = 75 799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR = 1.43, 95% CI = 1.09-1.89, P = 0.01), 1-year (OR = 1.46, 95% CI = 1.08-1.97, P = 0.01), and 3-year (OR = 1.37, 95% CI = 1.01-1.84, P = 0.04) graft survival. WL grafts were less associated with retransplantation (OR = 0.57; 95% CI = 0.41-0.80; P < 0.01), vascular complications (OR = 0.53, 95% CI = 0.38-0.74, P < 0.01) and biliary complications (OR = 0.67; 95% CI = 0.47-0.95; P = 0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany.,The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany
| | - Alireza Arefidoust
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany
| | - Omid Ghamarnejad
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Germany
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38
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Pinto MA, Grezzana-Filho TJM, Chedid AD, Leipnitz I, Prediger JE, Alvares-da-Silva MR, de Araújo A, Zahler S, Lopes BB, Giampaoli ÂZD, Kruel CRP, Chedid MF. Impact of intraoperative blood salvage and autologous transfusion during liver transplantation for hepatocellular carcinoma. Langenbecks Arch Surg 2020; 406:67-74. [PMID: 33025077 DOI: 10.1007/s00423-020-01997-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 09/22/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE Intraoperative blood salvage (IBS) with autologous blood transfusion is controversial in liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the role of IBS usage in LT for HCC. METHODS In a retrospective cohort study at a single center from 2002 to 2018, the outcomes of LT surgery for HCC were analyzed. Overall survival and disease-free survival of patients who received IBS were compared with those who did not receive IBS. Cancer recurrence, length of hospital stay, post-transplant complications, and blood loss also were evaluated. The primary aim of this study was to evaluate overall mid-term and long-term survival (4 and 6 years, respectively). RESULTS Of the total 163 patients who underwent LT for HCC in the study period, 156 had complete demographic and clinical data and were included in the study. IBS was used in 122 and not used in 34 patients. Ninety-five (60.9%) patients were men, and the mean patient age was 58.5 ± 7.6 years. The overall 1-year, 5-year, and 7-year survival in the IBS group was 84.2%, 67.7%, and 56.8% vs. 85.3%, 67.5%, and 67.5% in the non-IBS group (p = 0.77). The 1-year, 5-year, and 7-year disease-free survival in the IBS group was 81.6%, 66.5%, and 55.4% vs. 85.3%, 64.1%, and 64.1% in the non-IBS group (p = 0.74). For patients without complete HCC necrosis (n = 121), the 1-year, 5-year, and 7-year overall survival rates for those who received IBS (n = 95) were 86.2%, 67.7%, and 49.6% vs. 84.6%, 70.0%, and 70.0% for 26 patients without IBS (p = 0.857). For the same patients, the 1-year, 5-year, and 7-year disease-free survival in the IBS group was 84.0%, 66.8%, and 64.0% vs. 88.0%, 72.8%, and 72.8% in the non-IBS group (p = 0.690). CONCLUSION IBS does not appear to be associated with worse outcomes in patients undergoing LT for HCC, even in the presence of viable HCC in the explant. There seems to be no reason to contraindicate the use of IBS in LT for HCC.
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Affiliation(s)
- Marcelo A Pinto
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Tomaz J M Grezzana-Filho
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Aljamir D Chedid
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Ian Leipnitz
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - João E Prediger
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Mário R Alvares-da-Silva
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Alexandre de Araújo
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Sofia Zahler
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Bruno B Lopes
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Ângelo Z D Giampaoli
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Cleber R P Kruel
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil
| | - Marcio F Chedid
- Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Medical School of UFRGS, Porto Alegre, Brazil. .,Liver and Pancreas Transplant and Hepatobiliary Surgery Unit, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul (UFRGS, Rua Ramiro Barcelos 2350, 6th Floor, Room 600, Porto Alegre, 90035-903, Brazil.
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