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Knoedler L, Schaschinger T, Niederegger T, Hundeshagen G, Panayi AC, Cetrulo CL, Jeljeli M, Hofmann E, Heiland M, Koerdt S, Lellouch AG. Multi-Center Outcome Analysis of 16 Face Transplantations - A Retrospective OPTN Study. Transpl Int 2025; 38:14107. [PMID: 39944217 PMCID: PMC11813647 DOI: 10.3389/ti.2025.14107] [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: 11/22/2024] [Accepted: 01/09/2025] [Indexed: 05/09/2025]
Abstract
Facial Vascularized Composite Allotransplantation (fVCA) restores form and function for patients with severe facial disfigurements, yet multi-center outcome data remain scarce. We accessed the Organ Procurement and Transplantation Network (OPTN) database from 2008 to 2024 to identify all full- or partial-face fVCA recipients, excluding patients under 18 years and those with physiologically impossible BMIs. Of 25 identified patients, 16 (64%) met inclusion criteria (69% male; mean age 43 ± 14 years). Recipients experienced a median of 5 [IQR 0.0-10] acute rejection episodes, which correlated with inotrope use during donor procurement (p = 0.033). On average, patients were hospitalized 2.4 ± 1.8 times, with arginine vasopressin (AVP) administration linked to fewer hospitalizations (p = 0.035). Seven recipients (44%) experienced complications, and extended-criteria donor (ECD) status was associated with higher complication rates (p = 0.049). These findings underscore the promise of fVCA to address complex facial defects while identifying key risk factors-particularly inotrope use and ECD status, while AVP administration may mitigate hospital stays. Further studies with larger cohorts are warranted to refine perioperative strategies, improve outcomes, and expand the clinical utility of fVCA.
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Affiliation(s)
- Leonard Knoedler
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Thomas Schaschinger
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Tobias Niederegger
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Gabriel Hundeshagen
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
- Department of Plastic and Hand Surgery, Burn Center, BG Trauma Hospital Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - Adriana C. Panayi
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Curtis L. Cetrulo
- Vascularized Composite Allotransplantation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Maxime Jeljeli
- Vascularized Composite Allotransplantation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Elena Hofmann
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Max Heiland
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Steffen Koerdt
- Department of Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Alexandre G. Lellouch
- Vascularized Composite Allotransplantation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Shriners Children’s Boston, Boston, MA, United States
- Cedars-Sinai Medical Center, Los Angeles, CA, United States
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Incidence of Ischemia Reperfusion Injury Related Biliary Complications in Liver Transplantation: Effect of Different Types of Donors. Transplant Proc 2022; 54:1865-1873. [DOI: 10.1016/j.transproceed.2022.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 04/07/2022] [Accepted: 05/02/2022] [Indexed: 11/19/2022]
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Ghinolfi D, Melandro F, Torri F, Martinelli C, Cappello V, Babboni S, Silvestrini B, De Simone P, Basta G, Del Turco S. Extended criteria grafts and emerging therapeutics strategy in liver transplantation. The unstable balance between damage and repair. Transplant Rev (Orlando) 2021; 35:100639. [PMID: 34303259 DOI: 10.1016/j.trre.2021.100639] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 07/10/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023]
Abstract
Due to increasing demand for donor organs, "extended criteria" donors are increasingly considered for liver transplantation, including elderly donors and donors after cardiac death. The grafts of this subgroup of donors share a major risk to develop significant features of ischemia reperfusion injury, that may eventually lead to graft failure. Ex-situ machine perfusion technology has gained much interest in liver transplantation, because represents both a useful tool for improving graft quality before transplantation and a platform for the delivery of therapeutics directly to the organ. In this review, we survey ongoing clinical evidences supporting the use of elderly and DCD donors in liver transplantation, and the underlying mechanistic aspects of liver aging and ischemia reperfusion injury that influence graft quality and transplant outcome. Finally, we highlight evidences in the field of new therapeutics to test in MP in the context of recent findings of basic and translational research.
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Affiliation(s)
- Davide Ghinolfi
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy.
| | - Fabio Melandro
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy
| | - Francesco Torri
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy
| | - Caterina Martinelli
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy
| | - Valentina Cappello
- Center for Nanotechnology Innovation@NEST, Istituto Italiano di Tecnologia, Piazza S. Silvestro 12, 56127 Pisa, Italy
| | - Serena Babboni
- Institute of Clinical Physiology, CNR San Cataldo Research Area, via Moruzzi 1, 56124 Pisa, Italy
| | - Beatrice Silvestrini
- Department of Surgical, Medical, Molecular Pathology, and Critical Area, University of Pisa, 56122 Pisa, Italy.
| | - Paolo De Simone
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, 56124 Pisa, Italy
| | - Giuseppina Basta
- Institute of Clinical Physiology, CNR San Cataldo Research Area, via Moruzzi 1, 56124 Pisa, Italy
| | - Serena Del Turco
- Institute of Clinical Physiology, CNR San Cataldo Research Area, via Moruzzi 1, 56124 Pisa, Italy.
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Haque O, Yuan Q, Uygun K, Markmann JF. Evolving utilization of donation after circulatory death livers in liver transplantation: The day of DCD has come. Clin Transplant 2021; 35:e14211. [PMID: 33368701 PMCID: PMC7969458 DOI: 10.1111/ctr.14211] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 11/29/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022]
Abstract
Compared to donation after brain death (DBD), livers procured for transplantation from donation after circulatory death (DCD) donors experience more ischemia-reperfusion injury and higher rates of ischemic cholangiopathy due to the period of warm ischemic time (WIT) following withdrawal of life support. As a result, utilization of DCD livers for liver transplant (LT) has generally been limited to short WITs and younger aged donor grafts, causing many recovered DCD organs to be discarded without consideration for transplant. This study assesses how DCD liver utilization and outcomes have changed over time, using OPTN data from adult, first-time, deceased donor, whole-organ LTs between January 1995 and December 2019. Results show that increased clinical experience with DCD LT has translated into increased use of livers from DCD donors, shorter ischemic times, shorter lengths of hospitalization after transplant, and lower rates of retransplantation. The data also reveal that over the past decade, the rate of increase in DCD LTs conducted in the United States has outpaced that of DBD. Together, these trends signal an opportunity for the field of liver transplantation to mitigate the organ shortage by capitalizing on DCD liver allografts that are currently not being utilized.
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Affiliation(s)
- Omar Haque
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, MA, USA
- Shriners Hospitals for Children, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Qing Yuan
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- 8th Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Korkut Uygun
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard, Medical School, Boston, MA, USA
- Shriners Hospitals for Children, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - James F Markmann
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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Olivieri T, Magistri P, Guidetti C, Baroni S, Rinaldi S, Assirati G, Catellani B, Chierego G, Cantaroni C, Bondi F, Campagna A, Sangiorgi G, Pecchi A, Serra V, Tarantino G, Ballarin R, Guerrini GP, Girardis M, Bertellini E, Di Benedetto F. University of Modena Experience With Liver Grafts From Donation After Circulatory Death: What Really Matters in Organ Selection? Transplant Proc 2019; 51:2967-2970. [DOI: 10.1016/j.transproceed.2019.06.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/08/2019] [Accepted: 06/05/2019] [Indexed: 02/07/2023]
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Abstract
The debates about naming the unfolding times of anthropogenic global change the ‘Anthropocene’ are ultimately debates about the ‘human condition’. The proposal to amend the geological time scale by adding an ‘Anthropocene’ epoch (that is, the ‘Anthropocene proposal’ in its strict sense) is both an intra-geoscience debate about scientific sense-making and a debate about the societal context of the geosciences. This essay juxtaposes these debates, starting from three postulates: first, that the scientific methods of geological chronostratigraphy are applied rigorously; second, that anthropogenic global change is happening; and third, that the ‘Anthropocene proposal’ may be rejected if it does not meet the conditions required for its approval based on the rigorous application of the scientific methods of geological chronostratigraphy. These postulates are analysed through the lenses of the Cape Town Statement on Geoethics and the normative statements of the ‘geoethical promise’. It is found that an ethical quandary would arise if the ‘Anthropocene proposal’ were to be rejected. Consequently, and given the societal contexts of the geosciences, it is explored whether distinguishing between the geological past (as demarcated according to current chronostratigraphic methodology) and contemporary geological–historical times (characterised somewhat differently) could offer a work-around to tackle the quandary.
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Outcomes of Controlled Donation After Cardiac Death Compared With Donation After Brain Death in Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Proc 2018; 50:33-41. [PMID: 29407328 DOI: 10.1016/j.transproceed.2017.11.034] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/29/2017] [Accepted: 11/19/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Controlled donation after cardiac death (CDCD) is increasingly common for liver transplantation due to donor shortage. However, the outcomes, in terms of grafts and recipients, remain unclear. The current study is a systematic review and meta-analysis that compared CDCD with donation after brain death (DBD). METHODS We conducted an electronic search of MEDLINE, EMBASE, and the Cochrane Database (from January 2007 to May 2017). Studies reporting Maastricht category III or IV CDCD liver transplantation were screened for inclusion. We appraised studies using the Newcastle-Ottawa scale and meta-analyzed using a fixed or random effects model. RESULTS A total of 21 studies, with 12,035 patients, were included in data analysis. CDCD did not differ from DBD in patient survival (hazard ration: 1.20; 95% confidence interval [CI]: 0.98 to 1.47; P = .07), graft survival (hazard ratio: 1.24; 95% CI: 0.99 to 1.56; P = .06), primary nonfunction (odds ratio [OR]: 1.74; 95% CI: 1.00 to 3.03; P = .05), hepatic artery thrombosis (OR: 1.17; 95% CI: 0.78 to 1.74; P = .45). However, CDCD was associated with biliary complications (OR: 2.48; 95% CI: 2.05 to 3.00), retransplantation (OR: 2.54; 95% CI: 1.99 to 3.26), and peak alanine aminotransferase (weighted mean difference: 330.88; 95% CI: 259.88 to 401.87). A subgroup analysis that included only hepatitis C virus (HCV)-positive recipients showed no significant difference between CDCD and DBD in biliary complications (P = .16), retransplantion (P = .15), HCV recurrence (P = .20), and peak alanine aminotransferase (P = .06). CONCLUSIONS CDCD transplantation is the most viable alternative to DBD transplantation in the current critical shortage of liver organs. HCV infection may not be the inferior factor of postoperative outcomes and survival.
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Zhang R, Zhu ZJ, Sun LY. Application of Pediatric Donor Livers After Circulatory Death in Adult Liver Transplantation: A Single-Center Experience. EXP CLIN TRANSPLANT 2018; 16:575-581. [PMID: 29863456 DOI: 10.6002/ect.2017.0358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES This study aimed to investigate the outcomes of adult liver transplant procedures using grafts from pediatric donors after circulatory death. MATERIALS AND METHODS We retrospectively analyzed the data of 19 pediatric-to-adult liver transplant procedures from July 2013 to May 2016 in our hospital. Nineteen adult liver transplant procedures were performed using livers from pediatric donors after circulatory death. RESULTS We performed 18 orthotopic and 1 piggyback liver transplant procedure. The median graft-to-recipient weight ratio was 1.26% (range, 0.86% to 2.46%). The median warm and cold ischemia times were 11 minutes (range, 8-20 min) and 638 minutes (range, 200-843 min), respectively. Complications after the operation included postoperative pulmonary infection (8 patients), fungal infection (1 patient), cytomegalovirus infection (1 patient), hepatic artery thrombosis and biliary stricture (1 patient), portal vein stenosis (1 patient), and graft failure (2 patients). For patients with graft failure, 1 patient received retransplant and 1 died. The patients were followed for 22.44 months (range, 9.63-44.07 mo) after transplant and showed normal liver function and good health. The 3-year survival rates of grafts and patients were 89.47% and 94.74%, respectively. CONCLUSIONS Appropriate evaluation of donors and recipients and accurate intraoperative and postoperative treatment can ensure successful application of livers from pediatric donors after circulatory death in adult recipients.
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Affiliation(s)
- Rui Zhang
- From the Liver Transplantation Center, National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, China; and the Department of Hepatobiliary and Pancreatic Surgery, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China
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Townsend SA, Monga MA, Nightingale P, Mutimer D, Elsharkawy AM, Holt A. Hepatitis C Virus Recurrence Occurs Earlier in Patients Receiving Donation After Circulatory Death Liver Transplant Grafts Compared With Those Receiving Donation After Brainstem Death Grafts. Transplant Proc 2018; 49:2129-2134. [PMID: 29149973 DOI: 10.1016/j.transproceed.2017.07.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 06/13/2017] [Accepted: 07/30/2017] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist. METHODS This was a single-center study of all HCV + adults who underwent DCD liver transplantation between 2004 and 2014. 44 HCV+ patients received DCD grafts, and were matched with 44 HCV+ recipients of donation after brainstem death (DBD) grafts, and their outcomes examined. RESULTS The groups were matched for age, sex, and presence of hepatocellular carcinoma; no significant differences were found between the group's donor or recipient characteristics. Paired and unpaired analysis demonstrated that HCV recurrence was more rapid in recipients of DCD organs compared with DBD grafts (408 vs 657 days; P = .006). There were no significant differences in graft survival, patient survival, or rates of biliary complications between the cohorts despite DCD donors being 10 years older on average than those used in other published experience. CONCLUSIONS In an era of highly effective direct acting antiviral therapy, rapid HCV recrudescence in grafts from DCD donors should not compromise long-term morbidity or mortality. In the context of rising wait-list mortality, it is prudent to use all available sources to expand the pool of donor organs, and our data support the practice of using extended-criteria DCD grafts based on donor age. Notwithstanding that, clinicians should be aware that HCV recrudescence is more rapid in DCD recipients, and early post-transplant anti-viral therapy is indicated to prevent graft injury.
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Affiliation(s)
- S A Townsend
- Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom.
| | - M A Monga
- Good Hope Hospital, Rectory Road, Sutton Coldfield, Birmingham, United Kingdom
| | - P Nightingale
- Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom
| | - D Mutimer
- Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom
| | - A M Elsharkawy
- Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom
| | - A Holt
- Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, United Kingdom
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Xue S, He W, Zeng X, Tang Z, Feng S, Zhong Z, Xiong Y, Wang Y, Ye Q. Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway. Mol Med Rep 2018; 18:815-826. [PMID: 29845199 PMCID: PMC6059711 DOI: 10.3892/mmr.2018.9065] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 05/04/2018] [Indexed: 12/26/2022] Open
Abstract
Hypothermic machine perfusion (HMP) has been demonstrated to be a more effective method for preserving livers donated after circulatory death (DCD) than cold storage (CS); however, the underlying mechanisms remain unclear. The aim of the present study was to investigate the protective effects of HMP on rat DCD livers and the possible role of the nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. A total of 18 adult male rats were randomly divided into three groups: Control, HMP and CS (n=6 per group). To simulate the conditions of DCD liver transplantation, rat livers in the CS and HMP groups were subjected to 30 min warm ischemia following cardiac arrest and were then preserved by CS or HMP for 3 h. Subsequently, after 1 h of isolated reperfusion, the extent of ischemia/reperfusion injury (IRI) and cellular functions were assessed. During reperfusion, intrahepatic resistance and bile production were measured, and the perfusion fluid was collected for liver enzyme analysis. The liver tissues were then harvested for the assessment of malondialdehyde (MDA) production, superoxide dismutase (SOD) activity, ATP levels, as well as for histological analysis, immunohistochemistry and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Finally, the expression levels of the components associated with the Nrf2‑ARE signaling pathway were analyzed via western blotting and reverse transcription‑quantitative polymerase chain reaction. The results of the present study revealed that, compared with in the CS group, the HMP group exhibited higher levels of ATP, bile production and SOD activity, and improved histological results; however, lower levels of liver enzymes, apoptosis and MDA were detected. Additionally, the findings of the present study also suggested that the Nrf2‑ARE signaling pathway may be activated by the steady laminar flow of HMP. In conclusion, HMP may attenuate ischemia‑reperfusion injury to rat DCD livers via activation of the Nrf2‑ARE signaling pathway.
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Affiliation(s)
- Shuai Xue
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Weiyang He
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Xianpeng Zeng
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Zimei Tang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Shoucheng Feng
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Zibiao Zhong
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Yan Xiong
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Yanfeng Wang
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, P.R. China
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Sharma A, Kumar S, Dutta P, Kumar P, Attawar S. Extracorporeal support for donation after cardiac death: a new avatar of ECMO. Indian J Thorac Cardiovasc Surg 2017. [DOI: 10.1007/s12055-017-0519-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Abstract
Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.
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13
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Sher L, Quintini C, Fayek SA, Abt P, Lo M, Yuk P, Ji L, Groshen S, Case J, Marsh CL. Attitudes and barriers to the use of donation after cardiac death livers: Comparison of a United States transplant center survey to the united network for organ sharing data. Liver Transpl 2017; 23:1372-1383. [PMID: 28834180 DOI: 10.1002/lt.24855] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 08/06/2017] [Indexed: 02/07/2023]
Abstract
Transplantation of liver grafts from donation after cardiac death (DCD) is limited. To identify barriers of DCD liver utilization, all active US liver transplant centers (n = 138) were surveyed, and the responses were compared with the United Network for Organ Sharing (UNOS) data. In total, 74 (54%) centers responded, and diversity in attitudes was observed, with many not using organ and/or recipient prognostic variables defined in prior studies and UNOS data analysis. Most centers (74%) believed lack of a system allowing a timely retransplant is a barrier to utilization. UNOS data demonstrated worse 1- and 5-year patient survival (PS) and graft survival (GS) in DCD (PS, 86% and 64%; GS, 82% and 59%, respectively) versus donation after brain death (DBD) recipients (PS, 90% and 71%; GS, 88% and 69%, respectively). Donor alanine aminotransferase (ALT), recipient Model for End-Stage Liver Disease (MELD), and cold ischemia time (CIT) significantly impacted DCD outcomes to a greater extent than DBD outcomes. At 3 years, relisting and retransplant rates were 7.9% and 4.6% higher in DCD recipients. To optimize outcome, our data support the use of DCD liver grafts with CIT <6-8 hours in patients with MELD ≤ 20. In conclusion, standardization of donor and recipient criteria, defining the impact of ischemic cholangiopathy, addressing donor hospital policies, and developing a strategy for timely retransplant may help to expand the use of these organs. Liver Transplantation 23 1372-1383 2017 AASLD.
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Affiliation(s)
| | - Cristiano Quintini
- Liver Transplantation and HPB Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Sameh Adel Fayek
- Transplant Surgery, Medical City Transplant Institute-Fort Worth, Fort Worth, TX
| | - Peter Abt
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Mary Lo
- Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Pui Yuk
- Departments of Surgery, Los Angeles, CA
| | - Lingyun Ji
- Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Susan Groshen
- Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Jamie Case
- Scripps Center for Organ Transplantation, Scripps Clinic and Green Hospital, La Jolla, CA
| | - Christopher Lee Marsh
- Scripps Center for Organ Transplantation, Scripps Clinic and Green Hospital, La Jolla, CA
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14
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Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes. Transplantation 2017; 100:1513-24. [PMID: 27014794 DOI: 10.1097/tp.0000000000001175] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. METHODS Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. RESULTS Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. CONCLUSIONS Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.
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Eren EA, Latchana N, Beal E, Hayes D, Whitson B, Black SM. Donations After Circulatory Death in Liver Transplant. EXP CLIN TRANSPLANT 2016; 14:463-470. [PMID: 27733105 PMCID: PMC5461820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.
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Affiliation(s)
- Emre A. Eren
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Latchana
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Eliza Beal
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Don Hayes
- Departments of Pediatrics and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Section of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
| | - Bryan Whitson
- Department of Surgery, Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Sylvester M. Black
- Department of Surgery, Division of Transplantation, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Sutherland AI, Oniscu GC. Challenges and advances in optimizing liver allografts from donation after circulatory death donors. J Nat Sci Biol Med 2016; 7:10-5. [PMID: 27003962 PMCID: PMC4780154 DOI: 10.4103/0976-9668.175017] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
In recent years, there has been a shift in the donor demographics with an increase in donation after circulatory death (DCD). Livers obtained from DCD donors are known to have poorer outcomes when compared to donors after brainstem death and currently only a small proportion of DCD livers are used. This review outlines the recent technological developments in liver DCD donation, including clinical studies using normothermic regional perfusion and extracorporal machine perfusion of livers from DCD donors.
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Affiliation(s)
| | - Gabriel C Oniscu
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK
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First Comparison of Hypothermic Oxygenated PErfusion Versus Static Cold Storage of Human Donation After Cardiac Death Liver Transplants: An International-matched Case Analysis. Ann Surg 2016; 262:764-70; discussion 770-1. [PMID: 26583664 DOI: 10.1097/sla.0000000000001473] [Citation(s) in RCA: 284] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Exposure of donor liver grafts to prolonged periods of warm ischemia before procurement causes injuries including intrahepatic cholangiopathy, which may lead to graft loss. Due to unavoidable prolonged ischemic time before procurement in donation after cardiac death (DCD) donation in 1 participating center, each liver graft of this center was pretreated with the new machine perfusion "Hypothermic Oxygenated PErfusion" (HOPE) in an attempt to improve graft quality before implantation. METHODS HOPE-treated DCD livers (n = 25) were matched and compared with normally preserved (static cold preservation) DCD liver grafts (n = 50) from 2 well-established European programs. Criteria for matching included duration of warm ischemia and key confounders summarized in the balance of risk score. In a second step, perfused and unperfused DCD livers were compared with liver grafts from standard brain dead donors (n = 50), also matched to the balance of risk score, serving as baseline controls. RESULTS HOPE treatment of DCD livers significantly decreased graft injury compared with matched cold-stored DCD livers regarding peak alanine-aminotransferase (1239 vs 2065 U/L, P = 0.02), intrahepatic cholangiopathy (0% vs 22%, P = 0.015), biliary complications (20% vs 46%, P = 0.042), and 1-year graft survival (90% vs 69%, P = 0.035). No graft failure due to intrahepatic cholangiopathy or nonfunction occurred in HOPE-treated livers, whereas 18% of unperfused DCD livers needed retransplantation. In addition, HOPE-perfused DCD livers achieved similar results as control donation after brain death livers in all investigated endpoints. CONCLUSIONS HOPE seems to offer important benefits in preserving higher-risk DCD liver grafts.
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Liver Transplantation Using Grafts from Donation After Cardiac Death Donors. CURRENT SURGERY REPORTS 2015. [DOI: 10.1007/s40137-015-0105-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015; 43:1291-325. [PMID: 25978154 DOI: 10.1097/ccm.0000000000000958] [Citation(s) in RCA: 223] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.
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O'Neill S, Roebuck A, Khoo E, Wigmore SJ, Harrison EM. A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation. Transpl Int 2015; 27:1159-74. [PMID: 25052036 DOI: 10.1111/tri.12403] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 05/05/2014] [Accepted: 07/12/2014] [Indexed: 12/11/2022]
Abstract
Donation after cardiac death (DCD) liver transplantation is increasingly common but concerns exist over the development of biliary complications and ischemic cholangiopathy (IC). This study aimed to compare outcomes between DCD and donation after brain death (DBD) liver grafts. Studies reporting on post-transplantation outcomes after Maastricht category III DCD liver transplantation were screened for inclusion. Odds ratios (OR) with 95% confidence intervals were produced using random-effects models for the incidence of biliary complications, IC, graft and recipient survival. Meta-regression was undertaken to identify between-study predictors of effect size for biliary complications and IC. PROSPERO Record: CRD42012002113. Twenty-five studies with 62 184 liver transplant recipients (DCD = 2478 and DBD = 59 706) were included. In comparison with DBD, there was a significant increase in biliary complications [OR = 2.4 (1.9, 3.1); P < 0.00001] and IC [OR = 10.5 (5.7, 19.5); P < 0.00001] following DCD liver transplantation. In comparison with DBD, at 1 year [OR = 0.7 (0.5, 0.8); P = 0.0002] and 3 years [OR = 0.6 (0.5, 0.8); P = 0.001], there was a significant decrease in graft survival following DCD liver transplantation. At 1 year, there was also a nonsignificant decrease [OR = 0.8 (0.6, 1.0); P = 0.08] and by 3 years a significant decrease [OR = 0.7 (0.5, 1.0); P = 0.04] found in recipient survival following DCD liver transplantation. Eleven factors were entered into meta-regression models, but none explained the variability in effect size between studies. DCD liver transplantation is associated with an increase in biliary complications, IC, graft loss and mortality. Significant unexplained differences in effect size exist between centers.
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Affiliation(s)
- Stephen O'Neill
- MRC Centre for Inflammation Research, Tissue Injury and Repair Group, University of Edinburgh, Edinburgh, UK
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Outcomes Using Grafts from Donors after Cardiac Death. J Am Coll Surg 2015; 221:142-52. [PMID: 26095563 DOI: 10.1016/j.jamcollsurg.2015.03.053] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Revised: 03/25/2015] [Accepted: 03/25/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Previous reports suggest that donation after cardiac death (DCD) liver grafts have increased primary nonfunction (PNF) and cholangiopathy thought to be due to the graft warm ischemia before cold flushing. STUDY DESIGN In this single-center, retrospective study, 866 adult liver transplantations were performed at our institution from January 2005 to August 2014. Forty-nine (5.7%) patients received DCD donor grafts. The 49 DCD graft recipients were compared with all recipients of donation after brain death donor (DBD) grafts and to a donor and recipient age- and size-matched cohort. RESULTS The DCD donors were younger (age 28, range 8 to 60 years) than non-DCD (age 44.3, range 9 to 80 years) (p < 0.0001), with similar recipient age. The mean laboratory Model for End-Stage Liver Disease (MELD) was lower in DCD recipients (18.7 vs 22.2, p = 0.03). Mean cold and warm ischemia times were similar. Median ICU and hospital stay were 2 days and 7.5 days in both groups (p = 0.37). Median follow-ups were 4.0 and 3.4 years, respectively. Long-term outcomes were similar between groups, with similar 1-, 3- and 5-year patient and graft survivals (p = 0.59). Four (8.5%) recipients developed ischemic cholangiopathy (IC) at 2, 3, 6, and 8 months. Primary nonfunction and hepatic artery thrombosis did not occur in any patient in the DCD group. Acute kidney injury was more common with DCD grafts (16.3% of DCD recipients required dialysis vs 4.1% of DBD recipients, p = 0.01). An increased donor age (>40 years) was shown to increase the risk of IC (p = 0.006). CONCLUSIONS Careful selection of DCD donors can provide suitable donors, with results of liver transplantation comparable to those with standard brain dead donors.
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Ruebner RL, Reese PP, Abt PL. Donation after cardiac death liver transplantation is associated with increased risk of end-stage renal disease. Transpl Int 2014; 27:1263-71. [PMID: 25070497 DOI: 10.1111/tri.12409] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 07/20/2014] [Indexed: 12/27/2022]
Abstract
Limited organ supply has led to greater use of liver allografts with higher donor risk indices (DRI) and/or donated after cardiac death (DCD). DCD status is associated with acute kidney injury after liver transplantation; however, less is known about the association between donor quality and end-stage renal disease (ESRD). Using SRTR data, we assembled a cohort of liver transplant recipients from 2/2002 to 12/2010. We fit multivariable Cox regression models for ESRD. Model 1 included total DRI; model 2 included components of DRI, including DCD, as separate variables. Forty thousand four hundred and sixty-three liver transplant recipients were included. Median DRI was 1.40 (IQR 1.14, 1.72); 1822 (5%) received DCD livers. During median follow-up of 3.93 years, ESRD occurred in 2008 (5%) and death in 11 075 (27%) subjects. There was a stepwise increase in ESRD risk with higher DRI (DRI ≥1.14 and <1.40: HR 1.17, P = 0.06; DRI ≥1.40 and <1.72: HR 1.29, P = 0.003; DRI ≥1.72: HR 1.39, P < 0.001, compared with DRI <1.14). Adjusting for DRI components separately, DCD status was most strongly associated with ESRD (HR 1.40, P = 0.008). Higher DRI is associated with ESRD after liver transplantation, driven in part by DCD status. Donor quality is an important predictor of long-term renal outcomes in liver transplant recipients.
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Affiliation(s)
- Rebecca L Ruebner
- Division of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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Bazerbachi F, Selzner N, Seal JB, Selzner M. Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge. World J Transl Med 2014; 3:58-68. [DOI: 10.5528/wjtm.v3.i2.58] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Revised: 06/11/2014] [Accepted: 07/17/2014] [Indexed: 02/05/2023] Open
Abstract
The scarcity of donor livers has increased the interest in donation after cardiac death (DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusion models, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.
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Han M, Guo ZY, Zhao Q, Wang XP, Yuan XP, Jiao XY, Yang CH, Wang DP, Ju WQ, Wu LW, Hu AB, Tai Q, Ma Y, Zhu XF, He XS. Liver transplantation using organs from deceased organ donors: a single organ transplant center experience. Hepatobiliary Pancreat Dis Int 2014; 13:409-15. [PMID: 25100126 DOI: 10.1016/s1499-3872(14)60274-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program. METHODS From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively. RESULTS Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts. CONCLUSION With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.
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Affiliation(s)
- Ming Han
- Organ Transplant Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
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Abstract
The greatest challenge facing liver transplantation today is the shortage of donor livers. Demand far exceeds supply, and this deficit has driven expansion of what is considered an acceptable organ. The evolving standard has not come without costs, however, as each new frontier of expanded donor quality (i.e., advancing donor age, donation after cardiac death, and split liver) may have traded wait-list for post-transplant morbidity and mortality. This article delineates the nature and severity of risk associated with specific deceased donor liver characteristics and recommends strategies to maximally mitigate these risks.
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Affiliation(s)
- Sandy Feng
- Division of Abdominal Transplantation, Department of Surgery, University of California, 505 Parnassus Avenue, UCSF Box 0780, San Francisco, San Francisco, CA 94143, USA.
| | - Jennifer C Lai
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
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McElroy LM, Daud A, Davis AE, Lapin B, Baker T, Abecassis MM, Levitsky J, Holl JL, Ladner DP. A meta-analysis of complications following deceased donor liver transplant. Am J Surg 2014; 208:605-18. [PMID: 25118164 DOI: 10.1016/j.amjsurg.2014.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 05/14/2014] [Accepted: 06/09/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND Liver transplantation is a complex surgery associated with high rates of postoperative complications. While national outcomes data are available, national rates of most complications are unknown. DATA SOURCES A systematic review of the literature reporting rates of postoperative complications between 2002 and 2012 was performed. A cohort of 29,227 deceased donor liver transplant recipients from 74 studies was used to calculate pooled incidences for 17 major postoperative complications. CONCLUSIONS This is the first comprehensive review of postoperative complications after liver transplantation and can serve as a guide for transplant and nontransplant clinicians. Efforts to collect national data on complications, such as through the National Surgical Quality Improvement Program, would improve the ability to provide patients with informed consent, serve as a tool for individual center performance monitoring, and provide a central source against which to measure interventions aimed at improving patient care.
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Affiliation(s)
- Lisa M McElroy
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA.
| | - Amna Daud
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Ashley E Davis
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Brittany Lapin
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Talia Baker
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Michael M Abecassis
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Josh Levitsky
- Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
| | - Jane L Holl
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA
| | - Daniela P Ladner
- Center for Healthcare Studies, Institute for Public Health and Medicine, Chicago, IL, USA; Northwestern University Transplant Outcomes Research Collaborative (NUTORC), Comprehensive Transplant Center, Feinberg School of Medicine, Chicago, IL, USA
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Goldberg DS, Abt PL. Improving outcomes in DCDD liver transplantation: there can only be strength in numbers. Am J Transplant 2014; 14:1016-20. [PMID: 24712410 DOI: 10.1111/ajt.12697] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 01/21/2014] [Accepted: 02/04/2014] [Indexed: 01/25/2023]
Abstract
In the United States, liver transplantation using donation after circulatory determination of death (DCDD) donors is challenged by persistently inferior graft survival compared with donation after neurological death (DND), along with declining rates of liver transplantation relative to the total number of DCDD donors. Advances in adult-to-adult living donor liver transplantation graft survival temporally related to the Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium suggest that a similarly focused collaborative effort may serve to stimulate evolution within DCDD liver transplantation. Without a multi-center consortium to support innovative trials, the current state of DCDD liver transplantation is unlikely to progress.
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Affiliation(s)
- D S Goldberg
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
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Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: a systematic review and meta-analysis. Can J Gastroenterol Hepatol 2014; 28:103-8. [PMID: 24288695 PMCID: PMC4071895 DOI: 10.1155/2014/421451] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue. OBJECTIVE To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT. METHODS Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature. RESULTS The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I2=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I2=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I2=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I2=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I2=44%), and biliary complications. CONCLUSIONS While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.
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Luo Y, Ji WB, Duan WD, Ye S, Dong JH. Graft cholangiopathy: etiology, diagnosis, and therapeutic strategies. Hepatobiliary Pancreat Dis Int 2014; 13:10-7. [PMID: 24463074 DOI: 10.1016/s1499-3872(14)60001-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Graft cholangiopathy has been recognized as a significant cause of morbidity, graft loss, and even mortality in patients after orthotopic liver transplantation. The aim of this review is to analyze the etiology, pathogenesis, diagnosis and therapeutic strategies of graft cholangiopathy after liver transplantation. DATA SOURCE A PubMed database search was performed to identify articles relevant to liver transplantation, biliary complications and cholangiopathy. RESULTS Several risk factors for graft cholangiopathy after liver transplantation have been identified, including ischemia/reperfusion injury, cytomegalovirus infection, immunological injury and bile salt toxicity. A number of strategies have been attempted to prevent the development of graft cholangiopathy, but their efficacy needs to be evaluated in large clinical studies. Non-surgical approaches may offer good results in patients with extrahepatic lesions. For most patients with complex hilar and intrahepatic biliary abnormalities, however, surgical repair or re-transplantation may be required. CONCLUSIONS The pathogenesis of graft cholangiopathy after liver transplantation is multifactorial. In the future, more efforts should be devoted to the development of more effective preventative and therapeutic strategies against graft cholangiopathy.
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Affiliation(s)
- Ying Luo
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing 100853, China.
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31
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Timing of hepatic artery reperfusion and biliary strictures in liver transplantation. J Transplant 2013; 2013:757389. [PMID: 24368938 PMCID: PMC3866776 DOI: 10.1155/2013/757389] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 10/02/2013] [Accepted: 10/02/2013] [Indexed: 12/29/2022] Open
Abstract
During orthotopic liver transplantation (OLT), biliary tract perfusion occurs with hepatic artery reperfusion (HARP), commonly performed after the portal vein reperfusion (PVRP). We examined whether the average time interval between PVRP and HARP impacted on postoperative biliary strictures occurrence. Patients undergoing OLT from 2007 to 2009 were included if they were ≥18 years old, had survived 3 months postoperatively, and had data for PVRP and HARP. Patients receiving allografts from DCD donors were excluded. Patients were followed for 6 months post-OLT. Seventy-five patients met the study inclusion criteria. Of these, 10 patients had a biliary stricture. There was no statistical difference between those with and without biliary stricture in age, gender, etiology, MELD score, graft survival, and time interval between PVRP and HARP. Ninety percent of patients with biliary stricture had a PVRP-HARP time interval >30 minutes, as opposed to 77% of patients without biliary stricture. However, this was not statistically significant. The cold ischemia time was significantly different between the two groups. Time interval for HARP after PVRP did not appear to affect the development of biliary strictures. However, 30 minutes may be suggested as a critical time after which there is an increase in biliary stricture occurrence.
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[Liver transplant with donated graft after controlled cardiac death. Current situation]. Cir Esp 2013; 91:554-62. [PMID: 24021972 DOI: 10.1016/j.ciresp.2013.04.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 04/04/2013] [Accepted: 04/08/2013] [Indexed: 02/07/2023]
Abstract
An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review.
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Vanatta JM, Dean AG, Hathaway DK, Nair S, Modanlou KA, Campos L, Nezakatgoo N, Satapathy SK, Eason JD. Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death. EXP CLIN TRANSPLANT 2013; 11:154-163. [PMID: 23480344 DOI: 10.6002/ect.2012.0173] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. MATERIALS AND METHODS A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. RESULTS Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). CONCLUSIONS These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.
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Affiliation(s)
- Jason M Vanatta
- Department of Transplantation, University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, TN 38104, USA.
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Dageforde LA, Feurer ID, Pinson CW, Moore DE. Is liver transplantation using organs donated after cardiac death cost-effective or does it decrease waitlist death by increasing recipient death? HPB (Oxford) 2013; 15:182-9. [PMID: 23374358 PMCID: PMC3572278 DOI: 10.1111/j.1477-2574.2012.00524.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2012] [Accepted: 05/30/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the cost-effectiveness in liver transplantation (LT) of utilizing organs donated after cardiac death (DCD) compared with organs donated after brain death (DBD). METHODS A Markov-based decision analytic model was created to compare two LT waitlist strategies distinguished by organ type: (i) DBD organs only, and (ii) DBD and DCD organs. The model simulated outcomes for patients over 10 years with annual cycles through one of four health states: survival; ischaemic cholangiopathy; retransplantation, and death. Baseline values and ranges were determined from an extensive literature review. Sensitivity analyses tested model strength and parameter variability. RESULTS Overall survival is decreased, and biliary complications and retransplantation are increased in recipients of DCD livers. Recipients of DBD livers gained 5.6 quality-adjusted life years (QALYs) at a cost of US$69 000/QALY, whereas recipients on the DBD + DCD LT waitlist gained 6.0 QALYs at a cost of US$61 000/QALY. The DBD + DCD organ strategy was superior to the DBD organ-only strategy. CONCLUSIONS The extension of life and quality of life provided by DCD LT to patients on the waiting list who might otherwise not receive a liver transplant makes the continued use of DCD livers cost-effective.
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Affiliation(s)
| | - Irene D. Feurer
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - C. Wright Pinson
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Derek E. Moore
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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van der Hilst CS, IJtsma AJ, Bottema JT, van Hoek B, Dubbeld J, Metselaar HJ, Kazemier G, van den Berg AP, Porte RJ, Slooff MJ. The price of donation after cardiac death in liver transplantation: a prospective cost-effectiveness study. Transpl Int 2013; 26:411-8. [DOI: 10.1111/tri.12059] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Revised: 02/13/2013] [Accepted: 12/23/2012] [Indexed: 12/14/2022]
Affiliation(s)
- Christian S. van der Hilst
- Department of Surgery; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
| | - Alexander J.C. IJtsma
- Department of Surgery; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
| | - Jan T. Bottema
- Department of Surgery; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
| | - Bart van Hoek
- Department of Gastroenterology; Leiden University Medical Center; Leiden; The Netherlands
| | - Jeroen Dubbeld
- Department of Surgery; Leiden University Medical Center; Leiden; The Netherlands
| | - Herold J. Metselaar
- Department of Gastroenterology; Erasmus Medical Center; Rotterdam; The Netherlands
| | - Geert Kazemier
- Department of Surgery; Erasmus Medical Center; Rotterdam; The Netherlands
| | - Aad P. van den Berg
- Department of Gastroenterology; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
| | - Robert J. Porte
- Department of Surgery; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
| | - Maarten J.H. Slooff
- Department of Surgery; University Medical Center Groningen; University of Groningen; Groningen; The Netherlands
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Ciria R, Briceno J, Rufian S, Luque A, Lopez-Cillero P. Donation after cardiac death: where, when, and how? Transplant Proc 2013; 44:1470-4. [PMID: 22841187 DOI: 10.1016/j.transproceed.2012.05.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The continuing shortage of donors has led to the increasing use of marginal grafts. Surgical techniques such as split, domino, and living donations have not been able to decrease waiting list mortality. Donation after cardiac death (DCD) was the only source of grafts prior to the establishment of brain death criteria in 1968. Thereafter, donation after brain death emerged as the leading source of grafts. The context in which irreversible cessation of circulatory and respiratory functions happens was the cornerstone to definite the four categories of DCD by the First International Workshop on DCD held in Maastricht in 1995. Controlled (CDCD) and uncontrolled (UDCD) categories now account for 10%-20% of the donor pool in several countries. Despite initial high rates of primary nonfunction and ischemic-type biliary lesions, refinements in protocols and surgical techniques have led to excellent 1- and 3-year graft survivals of 80% and 70%, respectively with PNF and ITBL rates below 3%. The institution of UDCD and CDCD depends on legal considerations of presumed consent and withdrawal of maneuvers, respectively. The potential for DCD programs is huge; it may be the only real, effective way to increase the grafts pool, both in adult and pediatric populations. Recent advances in perfusion machines will surely optimize this donor pool and allow new therapies for graft resuscitation.
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Affiliation(s)
- R Ciria
- Unit of Liver Transplantation and Hepatobiliary Surgery, University Hospital Reina Sofia, Cordoba, Spain.
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Zhu XD, Shen ZY, Chen XG, Zang YJ. Pathotyping and clinical manifestations of biliary cast syndrome in patients after an orthotopic liver transplant. EXP CLIN TRANSPLANT 2012. [PMID: 23190361 DOI: 10.6002/ect.2012.0035] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES To summarize the pathotyping and clinical manifestations of biliary cast syndrome in patients after an orthotopic liver transplant. MATERIALS AND METHODS The clinical manifestations, auxiliary examination, therapeutic regimen, and clinical efficacy of 103 biliary cast syndrome patients who underwent an orthotopic liver transplant were retrospectively analyzed. Patients were divided into 6 groups from type 1 to type 6, according to the injury level of the biliary duct epithelium. RESULTS Many biliary cast syndrome patients showed symptoms including jaundice, dark urine, argillaceous stool, itchy skin, and fever. Serum levels of alanine aminotransferase, γ-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin were increased. In addition, total white cell counts in peripheral blood also were increased. T-tube cholangiography showed filling defects of various amounts. Optical fiber choledochoscope examination revealed that the biliary tract was filled with solid substances, and necrosis of the biliary tract epithelium was observed in some biliary cast syndrome patients. From type 1 to type 6 biliary cast syndrome patients, the probability of clinical symptoms and biliary tract stricture gradually increased, the time needed for supporting gradually prolonged after removal of the biliary cast, and T-tube cholangiography showed that the filling defects gradually expanded. CONCLUSIONS Clinical manifestations and cholangiography presentations mainly depend on pathotyping.
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Affiliation(s)
- Xiao-dan Zhu
- From the Liver Transplantation Institute of Armed Police Force, General Hospital of Chinese Armed Police Force, Beijing 100039, China.
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Le Dinh H, de Roover A, Kaba A, Lauwick S, Joris J, Delwaide J, Honoré P, Meurisse M, Detry O. Donation after cardio-circulatory death liver transplantation. World J Gastroenterol 2012; 18:4491-506. [PMID: 22969222 PMCID: PMC3435774 DOI: 10.3748/wjg.v18.i33.4491] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2011] [Revised: 03/27/2012] [Accepted: 03/29/2012] [Indexed: 02/06/2023] Open
Abstract
The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT.
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Reich DJ, Guy SR. Donation After Cardiac Death in Abdominal Organ Transplantation. ACTA ACUST UNITED AC 2012; 79:365-75. [DOI: 10.1002/msj.21309] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Harring TR, Nguyen NTT, Cotton RT, Guiteau JJ, Salas de Armas IA, Liu H, Goss JA, O'Mahony CA. Liver transplantation with donation after cardiac death donors: a comprehensive update. J Surg Res 2012; 178:502-11. [PMID: 22583594 DOI: 10.1016/j.jss.2012.04.044] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Revised: 03/29/2012] [Accepted: 04/20/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND Use of donation after cardiac death (DCD) donors has been proposed as an effective way to expand the availability of hepatic allografts used in orthotopic liver transplantation (OLT); yet, there remains no consensus in the medical literature as to how to choose optimal recipients and donors based on available information. METHODS We queried the United Network of Organ Sharing/Organ Procurement and Transplantation Network database for hepatic DCD allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic allografts from donation-after-brain-death (DBD) donors, and 2351 patients received hepatic allografts from DCD donors. We performed survival analysis using log-rank and Kaplan-Meier tests. We performed univariate and multivariate analyses using the Cox proportional hazards model. All statistics were performed with SPSS 15.0. RESULTS Patients receiving hepatic DCD allografts had significantly worse survival compared with patients receiving hepatic DBD allografts. Pediatric patients who received a hepatic DCD allograft had similar survival to those who received a hepatic DBD allograft. The optimal recipient-related characteristics were age <50 y, International Normalized Ratio <2.0, albumin >3.5 gm/dL, and cold ischemia time <8 h; optimal donor-related characteristics included age <50 y and donor warm ischemia time <20 min. CONCLUSIONS By identifying certain characteristics, the transplant clinician's decision-making process can be assisted so that similar survival outcomes after OLT can be achieved with the use of hepatic DCD allografts.
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Affiliation(s)
- Theresa R Harring
- Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
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Uemura T, Nikkel LE, Hollenbeak CS, Ramprasad V, Schaefer E, Kadry Z. How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C? Transpl Int 2012; 25:671-9. [DOI: 10.1111/j.1432-2277.2012.01474.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Uemura T, Ramprasad V, Hollenbeak CS, Bezinover D, Kadry Z. Liver transplantation for hepatitis C from donation after cardiac death donors: an analysis of OPTN/UNOS data. Am J Transplant 2012; 12:984-91. [PMID: 22225523 DOI: 10.1111/j.1600-6143.2011.03899.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Donation after cardiac death (DCD) liver transplantation is increasing largely because of a shortage of organs. However, there are almost no data that have specifically assessed the impact of using DCD livers for HCV patients. We retrospectively studied adult primary DCD liver transplantation (630 HCV, 1164 non-HCV) and 54 129 donation after brain death (DBD) liver transplantation between 2002 and 2009 using the UNOS/OPTN database. With donation after brain death (DBD) livers, HCV recipients had significantly inferior graft survival compared to non-HCV recipients (p < 0.0001). Contrary to DBD donors, DCD livers used in HCV patients showed no difference in graft survival compared to non-HCV patients (p = 0.5170). Cox models showed DCD livers and HCV disease had poorer graft survival (HR = 1.80 and 1.28, p < 0.0001, respectively). However, the hazard ratio of DCD and HCV interaction was 0.80 (p = 0.02) and these results suggest that DCD livers on HCV disease do not fare worse than DCD livers on non-HCV disease. The graft survival of recent years (2006-2009) was significantly better than that in former years (2002-2005) (p = 0.0482). In conclusion, DCD liver transplantation for HCV disease showed satisfactory outcomes. DCD liver transplantation can be valuable option for HCV related end-stage liver disease.
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Affiliation(s)
- T Uemura
- Division of Transplantation, Department of Surgery, Penn State University, College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
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Manara AR, Murphy PG, O'Callaghan G. Donation after circulatory death. Br J Anaesth 2012; 108 Suppl 1:i108-21. [PMID: 22194426 DOI: 10.1093/bja/aer357] [Citation(s) in RCA: 200] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Donation after circulatory death (DCD) describes the retrieval of organs for the purposes of transplantation that follows death confirmed using circulatory criteria. The persisting shortfall in the availability of organs for transplantation has prompted many countries to re-introduce DCD schemes not only for kidney retrieval but increasingly for other organs with a lower tolerance for warm ischaemia such as the liver, pancreas, and lungs. DCD contrasts in many important respects to the current standard model for deceased donation, namely donation after brain death. The challenge in the practice of DCD includes how to identify patients as suitable potential DCD donors, how to support and maintain the trust of bereaved families, and how to manage the consequences of warm ischaemia in a fashion that is professionally, ethically, and legally acceptable. Many of the concerns about the practice of both controlled and uncontrolled DCD are being addressed by increasing professional consensus on the ethical and legal justification for many of the interventions necessary to facilitate DCD. In some countries, DCD after the withdrawal of active treatment accounts for a substantial proportion of deceased organ donors overall. Where this occurs, there is an increased acceptance that organ and tissue donation should be considered a routine part of end-of-life care in both intensive care unit and emergency department.
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Affiliation(s)
- A R Manara
- The Intensive Care Unit, Frenchay Hospital, Frenchay Park Road, Bristol BS16 1LE, UK.
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Skaro AI, Wang E, Lyuksemburg V, Abecassis M. Donation after cardiac death liver transplantation: time for policy to catch up with practice. Liver Transpl 2012; 18:5-8. [PMID: 22140021 DOI: 10.1002/lt.22478] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Bellingham JM, Santhanakrishnan C, Neidlinger N, Wai P, Kim J, Niederhaus S, Leverson GE, Fernandez LA, Foley DP, Mezrich JD, Odorico JS, Love RB, De Oliveira N, Sollinger HW, D'Alessandro AM. Donation after cardiac death: a 29-year experience. Surgery 2011; 150:692-702. [PMID: 22000181 DOI: 10.1016/j.surg.2011.07.057] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Accepted: 07/11/2011] [Indexed: 01/12/2023]
Abstract
OBJECTIVE To report the long-term outcomes of 1218 organs transplanted from donation after cardiac death (DCD) donors from January 1980 through December 2008. METHODS One-thousand two-hundred-eighteen organs were transplanted into 1137 recipients from 577 DCD donors. This includes 1038 kidneys (RTX), 87 livers (LTX), 72 pancreas (PTX), and 21 DCD lungs. The outcomes were compared with 3470 RTX, 1157 LTX, 903 PTX, and 409 lung transplants from donors after brain death (DBD). RESULTS Both patient and graft survival is comparable between DBD and DCD transplant recipients for kidney, pancreas, and lung after 1, 3, and 10 years. Our findings reveal a significant difference for patient and graft survival of DCD livers at each of these time points. In contrast to the overall kidney transplant experience, the most recent 16-year period (n = 396 DCD and 1,937 DBD) revealed no difference in patient and graft survival, rejection rates, or surgical complications but delayed graft function was higher (44.7% vs 22.0%; P < .001). In DCD LTX, biliary complications (51% vs 33.4%; P < .01) and retransplantation for ischemic cholangiopathy (13.9% vs 0.2%; P < .01) were increased. PTX recipients had no difference in surgical complications, rejection, and hemoglobin A1c levels. Surgical complications were equivalent between DCD and DBD lung recipients. CONCLUSION This series represents the largest single center experience with more than 1000 DCD transplants and given the critical demand for organs, demonstrates successful kidney, pancreas, liver, and lung allografts from DCD donors.
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Affiliation(s)
- Janet M Bellingham
- Division of Organ Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375, USA
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Perera MTP, Bramhall SR. Current status and recent advances of liver transplantation from donation after cardiac death. World J Gastrointest Surg 2011; 3:167-76. [PMID: 22180833 PMCID: PMC3240676 DOI: 10.4240/wjgs.v3.i11.167] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2011] [Revised: 10/21/2011] [Accepted: 10/28/2011] [Indexed: 02/06/2023] Open
Abstract
The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably “prematurely” offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.
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Affiliation(s)
- M Thamara Pr Perera
- M Thamara PR Perera, Simon R Bramhall, The Liver Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom
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Increased risk of severe recurrence of hepatitis C virus in liver transplant recipients of donation after cardiac death allografts. Transplantation 2011; 92:686-9. [PMID: 21832962 DOI: 10.1097/tp.0b013e31822a79d2] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND In hepatitis C virus (HCV) recipients of donation after cardiac death (DCD) grafts, there is suggestion of lower rates of graft survival, indicating that DCD grafts themselves may represent a significant risk factor for severe recurrence of HCV. METHODS We evaluated all DCD liver transplant recipients from August 2006 to February 2011 at our center. Recipients with HCV who received a DCD graft (group 1, HCV+ DCD, n=17) were compared with non-HCV recipients transplanted with a DCD graft (group 2, HCV- DCD, n=15), and with a matched group of HCV recipients transplanted with a donation after brain death (DBD) graft (group 3, HCV+ DBD, n=42). RESULTS A trend of poorer graft survival was seen in HCV+ patients who underwent a DCD transplant (group 1) compared with HCV- patients who underwent a DCD transplant (group 2) (P=0.14). Importantly, a statistically significant difference in graft survival was seen in HCV+ patients undergoing DCD transplant (group 1) (73%) as compared with DBD transplant (group 3) (93%)(P=0.01). There was a statistically significant increase in HCV recurrence at 3 months (76% vs. 16%) (P=0.005) and severe HCV recurrence within the first year (47% vs. 10%) in the DCD group (P=0.004). CONCLUSIONS HCV recurrence is more severe and progresses more rapidly in HCV+ recipients who receive grafts from DCD compared with those who receive grafts from DBD. DCD liver transplantation in HCV+ recipients is associated with a higher rate of graft failure compared with those who receive grafts from DBD. Caution must be taken when using DCD grafts in HCV+ recipients.
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Abstract
Over the past decade, use of ECD organs for OLT has allowed many transplant programs to afford patients access to an otherwise scarce resource and to maintain center volume. Although overall posttransplant outcomes are inferior to results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD organs significantly lowers median wait-times for OLT, MELD score at OLT, and death while awaiting transplantation. It is incumbent on the transplant community to provide continued scrutiny of the many factors involved in ECD organ utilization, evaluate the degree of risk and benefit such allografts may impart on particular recipients, and thereby provide suitable “matching” to maximize favorable outcomes. Transplant caregivers need to provide patients with evidence-based care decisions, be good stewards of a scarce resource, and maintain threshold survival results for their programs. This requires balancing the urgency with which a transplant is needed and the utility of such a transplant. There is a clear necessity to pursue additional donor research to improve use of these marginal grafts and assess interventions that enhance the safety of ECD livers.
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Ali AA, White P, Xiang B, Lin HY, Tsui SS, Ashley E, Lee TW, Klein JRH, Kumar K, Arora RC, Large SR, Tian G, Freed DH. Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs. Am J Transplant 2011; 11:1621-32. [PMID: 21749639 DOI: 10.1111/j.1600-6143.2011.03622.x] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Cardiac transplantation is in decline, in contrast to other solid organs where the number of solid organ transplants from donors after circulatory death (DCD) is increasing. Hearts from DCD donors are not currently utilized due to concerns that they may suffer irreversible cardiac injury with resultant poor graft function. Using a large animal model, we tested the hypothesis that hearts from DCD donors would be suitable for transplantation. Donor pigs were subjected to hypoxic cardiac arrest (DCD) followed by 15 min of warm ischemia and resuscitation on cardiopulmonary bypass, or brainstem death (BSD) via intracerebral balloon inflation. Cardiac function was assessed through load-independent measures and magnetic resonance imaging and spectroscopy. After resuscitation, DCD hearts had near normal contractility, although stroke volume was reduced, comparable to BSD hearts. DCD hearts had a significant decline in phosphocreatine and increase in inorganic phosphate during the hypoxic period, with a return to baseline levels after reperfusion. After transplantation, cardiac function was comparable between BSD and DCD groups. Therefore, in a large animal model, the DCD heart maintains viability and recovers function similar to that of the BSD heart and may be suitable for clinical transplantation. Further study is warranted on optimal reperfusion strategies.
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Affiliation(s)
- A A Ali
- Papworth Hospital, Cambridge, UK
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Karp SJ, Johnson S, Evenson A, Curry MP, Manning D, Malik R, Lake-Bakaar G, Lai M, Hanto D. Minimising cold ischaemic time is essential in cardiac death donor-associated liver transplantation. HPB (Oxford) 2011; 13:411-6. [PMID: 21609374 PMCID: PMC3103098 DOI: 10.1111/j.1477-2574.2011.00307.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND An important issue in the transplantation of livers procured from cardiac death donors (CDDs) concerns why some centres report equivalent outcomes and others report inferior outcomes in transplantations using CDD organs compared with standard criteria donor (SCD) organs. Resolving this discrepancy may increase the number of usable organs. OBJECTIVES This study aimed to test whether differences in cold ischaemic time (CIT) are critical during CDD organ transplantation and whether such differences might explain the disparate outcomes. METHODS Results of CDD liver transplants in our own centre were compared retrospectively with results in a matched cohort of SCD liver recipients. Endpoints of primary non-function (PNF) and ischaemic cholangiopathy (IC) were used because these outcomes are clearly associated with CDD organ use. RESULTS In 22 CDD organ transplants, CIT was a strong predictor of PNF or IC (P = 0.021). Minimising CIT in CDD organ transplants produced outcomes similar to those in a matched SCD organ transplant cohort at our centre and in SCD organ transplant results nationally (1- and 3-year graft and patient survival rates: 90.9% and 73.3% vs. 77.6% and 69.2% in CDD and SCD grafts, respectively. A review of the published literature demonstrated that centres with higher CITs tend to have higher rates of PNF or IC (correlation coefficient: 0.41). CONCLUSIONS These findings suggest that a targeted effort to minimise CIT might improve outcomes and allow the safer use of CDD organs.
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Affiliation(s)
- Seth J Karp
- Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
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