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Archie WH, Baimas-George M, Haynes N, Kundu S, Peterson K, Wehrle CJ, Huckleberry D, Eskind L, Levi D, Soto JR, Denny R, Casingal V, Cochran A, Rein EH, Vrochides D. Upper limit of normothermic machine preservation of liver grafts from donation after circulatory death yet to be defined. World J Transplant 2025; 15:99170. [DOI: 10.5500/wjt.v15.i2.99170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/07/2024] [Accepted: 12/11/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND The normothermic machine perfusion pump (NMPP) could shape the future of transplantation. Providing ex-vivo optimization, NMPP attenuates ischemic insult while replenishing energy. An understanding of machine perfusion time (MPT) impact and potential clinical benefits is paramount and necessitates exploration.
AIM To investigate the relationship between MPT and post-transplant graft function.
METHODS Retrospective review of the first 50 donation after circulatory death (DCD) grafts preserved using NMPP in a tertiary institution was performed. Essential preservation time points, graft parameters, recipient information, and postoperative outcomes were prospectively recorded. Early allograft dysfunction (EAD), L-Graft7 score and 90-day outcomes were collected for all grafts. The first 20 recipients were allocated into the early group, considered the learning curve population for the center. The subsequent 30 were allocated into the late group. Recipients were also stratified into cohorts depending on MPT, i.e., short (< 8 hours), medium (8-16 hours) and long (> 16 hours).
RESULTS NMPP operational parameters were not predictive of EAD, L-GrAFT7 or 90-day outcomes. The early group had significantly less MPT and cold ischemia time than the late group (553 minutes vs 850 minutes, P < 0.001) and (127.5 minutes vs 154 minutes, P = 0.025), respectively. MPT had no impact in either group.
CONCLUSION Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population, indicating its upper limits, likely beyond 24 hours, are not demonstrated within this study. Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and, if the latter, what is the maximum safe duration. Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.
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Affiliation(s)
- William H Archie
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Maria Baimas-George
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Nathanael Haynes
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Souma Kundu
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Katheryn Peterson
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Chase J Wehrle
- Department of Hepato-Pancreato-Biliary/Liver Transplant Surgery, Cleveland Clinic Transplant Research Center, Cleveland, OH 44195, United States
| | - Damien Huckleberry
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Lon Eskind
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - David Levi
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Jose R Soto
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Roger Denny
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Vincent Casingal
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Allyson Cochran
- Department of Surgery, Carolinas Center for Surgical Outcomes Science, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Erin H Rein
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
| | - Dionisios Vrochides
- Division of Adominal Transplant, Department of Surgery, Carolinas Medical Center, Charlotte, NC 28203, United States
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Canizares S, Montalvan A, Chumdermpadetsuk R, Modest A, Eckhoff D, Lee DD. Liver machine perfusion technology: Expanding the donor pool to improve access to liver transplantation. Am J Transplant 2024; 24:1664-1674. [PMID: 38508317 DOI: 10.1016/j.ajt.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 03/01/2024] [Accepted: 03/11/2024] [Indexed: 03/22/2024]
Abstract
The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a differences-in-differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization. We found a significant increase in cold ischemia time and organs with donor warm ischemia time over 30 minutes (P < .05). After removing one outlier center, the analysis showed that these centers through MP accepted overall more donation after circulatory death donors, donation after circulatory death donors over 50 years old, donors with macrovesicular steatosis greater than 30% on liver biopsy, and donor warm ischemia time over 30 minutes (P < .05). MP has allowed centers to expand their use of extended-criteria donors beyond traditional cutoffs and to increase patient access to liver transplantation.
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Affiliation(s)
- Stalin Canizares
- Division of Transplant Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Adriana Montalvan
- Division of Transplant Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ritah Chumdermpadetsuk
- Division of Transplant Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Anna Modest
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts, USA
| | - Devin Eckhoff
- Division of Transplant Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - David D Lee
- Division of Transplant Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
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Shimada S, Yoshida A, Abouljoud M, Miyake K, Ivanics T, Shamaa T, Venkat D, Moonka D, Trudeau S, Reed E, Nagai S. Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy. Clin Transplant 2024; 38:e15190. [PMID: 37964683 DOI: 10.1111/ctr.15190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 09/30/2023] [Accepted: 10/28/2023] [Indexed: 11/16/2023]
Abstract
BACKGROUND After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.
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Affiliation(s)
- Shingo Shimada
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Katsunori Miyake
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Deepak Venkat
- Division of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, USA
| | - Dilip Moonka
- Division of Gastroenterology and Hepatology, Henry Ford Health, Detroit, Michigan, USA
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan, USA
| | - Elizabeth Reed
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Health, Detroit, Michigan, USA
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Ishaque T, Eagleson MA, Bowring MG, Motter JD, Yu S, Luo X, Kernodle AB, Gentry S, Garonzik-Wang JM, King EA, Segev DL, Massie AB. Transplant Candidate Outcomes After Declining a DCD Liver in the United States. Transplantation 2023; 107:e339-e347. [PMID: 37726882 PMCID: PMC11537495 DOI: 10.1097/tp.0000000000004777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/21/2023]
Abstract
BACKGROUND In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. METHODS Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. RESULTS Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. CONCLUSIONS DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.
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Affiliation(s)
- Tanveen Ishaque
- New York University Langone Transplant Institute, New York, New York, USA
| | | | - Mary G. Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jennifer D. Motter
- New York University Langone Transplant Institute, New York, New York, USA
| | - Sile Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Xun Luo
- University Hospitals/Case Western Reserve University, Cleveland, Ohio, United States
| | - Amber B. Kernodle
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sommer Gentry
- New York University Langone Transplant Institute, New York, New York, USA
- New York University Grossman School of Medicine, New York, New York, USA
- Scientific Registry of Transplant Recipients, Minneapolis, MN
| | | | - Elizabeth A. King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- New York University Langone Transplant Institute, New York, New York, USA
- New York University Grossman School of Medicine, New York, New York, USA
- Scientific Registry of Transplant Recipients, Minneapolis, MN
| | - Allan B. Massie
- New York University Langone Transplant Institute, New York, New York, USA
- New York University Grossman School of Medicine, New York, New York, USA
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Meier RPH, Nunez M, Syed SM, Feng S, Tavakol M, Freise CE, Roberts JP, Ascher NL, Hirose R, Roll GR. DCD liver transplant in patients with a MELD over 35. Front Immunol 2023; 14:1246867. [PMID: 37731493 PMCID: PMC10507358 DOI: 10.3389/fimmu.2023.1246867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 08/17/2023] [Indexed: 09/22/2023] Open
Abstract
Introduction Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.
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Affiliation(s)
- Raphael P. H. Meier
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Miguel Nunez
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Shareef M. Syed
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Sandy Feng
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Mehdi Tavakol
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Chris E. Freise
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Nancy L. Ascher
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Garrett R. Roll
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
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Al-Ameri AAM, Zhou Z, Zheng S. Comparative Analysis of Donor Liver Allograft Outcomes in Hepatocellular Carcinoma Patients Who Underwent Liver Transplant. EXP CLIN TRANSPLANT 2023; 21:664-670. [PMID: 37698401 DOI: 10.6002/ect.2023.0119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
OBJECTIVES Liver transplant for patients with hepatocellular carcinoma involves 3 main types of donor allografts: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Data on this topic are limited, and controversies exist regarding liver transplant outcomes in hepatocellular carcinoma patients who have received these allografts. MATERIALS AND METHODS Data from 490 hepatocellular carcinoma patients who received liver transplant from 2015 to 2021 at the Shulan (Hangzhou) Hospital were retrospectively analyzed. Participants were divided into 3 cohorts according to allograft type: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Kaplan-Meier and Cox regression methods were used to evaluate patient survival, graft survival, and recurrence-free survival rates after liver transplant. RESULTS Kaplan-Meier analysis revealed that 3-year patient survival rates were 69.2% for donations after brain death, 69.2% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .42); the 3-year graft survival rates were 53.3% for donations after brain death, 56.4% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .44); and 3-year recurrence-free survival rates were 55% for donations after brain death, 56.6% for donations after cardiac death, and 39.5% for donations after brain and cardiac death (P = .46). Complications were also similar across the 3 cohorts (P = .36). Multivariable analysis showed that intraoperative red blood cell transfusion (hazard ratio: 1.820; P = .042) and early allograft dysfunction (hazard ratio: 3.240; P = .041) were independent risk factors for graft survival. CONCLUSIONS Similar outcomes can be achieved for hepatocellular carcinoma patients who undergo liver transplant with donations after brain death, donations after cardiac death, or donations after brain and cardiac death allografts, especially when strict donor selection criteria are applied.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- >From the Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; the Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China; and the NHC Key Laboratory of Combined Multi-organ Transplantation, the Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, and the Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou China
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Handley TJ, Arnow KD, Melcher ML. Despite Increasing Costs, Perfusion Machines Expand the Donor Pool of Livers and Could Save Lives. J Surg Res 2023; 283:42-51. [PMID: 36368274 DOI: 10.1016/j.jss.2022.10.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 08/27/2022] [Accepted: 10/07/2022] [Indexed: 11/11/2022]
Abstract
INTRODUCTION Liver transplantation is a highly successful treatment for liver failure and disease. However, demand continues to outstrip our ability to provide transplantation as a treatment. Many livers initially considered for transplantation are not used because of concerns about their viability or logistical issues. Recent clinical trials have shown discarded livers may be viable if they undergo machine perfusion, which allows a more objective assessment of liver quality. METHODS Using the Scientific Registry of Transplant Recipients dataset, we examined discarded and unretrieved organs to determine their eligibility for perfusion. We then used a Markov decision-analytic model to perform a cost-effectiveness analysis of two competing transplant strategies: Static Cold Storage (SCS) alone versus Static Cold Storage and Normothermic Machine Perfusion (NMP) of discarded organs. RESULTS The average predicted successful transplants after perfusion was 385, representing a 5.8% increase in the annual yield of liver transplants. Our cost-effectiveness analysis found that the SCS strategy generated 4.64 quality-adjusted life years (QALYs) and cost $479,226. The combined SCS + NMP strategy generated 4.72 QALYs and cost $481,885. The combined SCS + NMP strategy had an incremental cost-effectiveness ratio of $33,575 per additional QALY over the 10-year study horizon. CONCLUSIONS Machine perfusion of livers currently not considered viable for transplant could increase the number of transplantable grafts by approximately 5% per year and is cost-effective compared to Static Cold Storage alone.
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Affiliation(s)
- Thomas J Handley
- Department of Health Policy, Stanford University School of Medicine, Stanford, California; Stanford-Surgery Policy Improvement Research & Education Center (S-SPIRE), Stanford, California; Department of Surgery, Stanford University School of Medicine, Stanford, California.
| | - Katherine D Arnow
- Stanford-Surgery Policy Improvement Research & Education Center (S-SPIRE), Stanford, California
| | - Marc L Melcher
- Department of Surgery, Stanford University School of Medicine, Stanford, California
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8
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Meier RPH, Kelly Y, Braun H, Maluf D, Freise C, Ascher N, Roberts J, Roll G. Comparison of Biliary Complications Rates After Brain Death, Donation After Circulatory Death, and Living-Donor Liver Transplantation: A Single-Center Cohort Study. Transpl Int 2022; 35:10855. [PMID: 36568142 PMCID: PMC9780276 DOI: 10.3389/ti.2022.10855] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022]
Abstract
Donation-after-circulatory-death (DCD), donation-after-brain-death (DBD), and living-donation (LD) are the three possible options for liver transplantation (LT), each with unique benefits and complication rates. We aimed to compare DCD-, DBD-, and LD-LT-specific graft survival and biliary complications (BC). We collected data on 138 DCD-, 3,027 DBD- and 318 LD-LTs adult recipients from a single center and analyzed patient/graft survival. BC (leak and anastomotic/non-anastomotic stricture (AS/NAS)) were analyzed in a subset of 414 patients. One-/five-year graft survival were 88.6%/70.0% for DCD-LT, 92.6%/79.9% for DBD-LT, and, 91.7%/82.9% for LD-LT. DCD-LTs had a 1.7-/1.3-fold adjusted risk of losing their graft compared to DBD-LT and LD-LT, respectively (p < 0.010/0.403). Bile leaks were present in 10.1% (DCD-LTs), 7.2% (DBD-LTs), and 36.2% (LD-LTs) (ORs, DBD/LD vs. DCD: 0.7/4.2, p = 0.402/<0.001). AS developed in 28.3% DCD-LTs, 18.1% DBD-LTs, and 43.5% LD-LTs (ORs, DBD/LD vs. DCD: 0.5/1.8, p = 0.018/0.006). NAS was present in 15.2% DCD-LTs, 1.4% DBDs-LT, and 4.3% LD-LTs (ORs, DBD/LD vs. DCD: 0.1/0.3, p = 0.001/0.005). LTs w/o BC had better liver graft survival compared to any other groups with BC. DCD-LT and LD-LT had excellent graft survival despite significantly higher BC rates compared to DBD-LT. DCD-LT represents a valid alternative whose importance should increase further with machine/perfusion systems.
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Affiliation(s)
- Raphael Pascal Henri Meier
- University of California, San Francisco, San Francisco, CA, United States,University of Maryland, Baltimore, Baltimore, MD, United States,*Correspondence: Raphael Pascal Henri Meier,
| | - Yvonne Kelly
- University of California, San Francisco, San Francisco, CA, United States
| | - Hillary Braun
- University of California, San Francisco, San Francisco, CA, United States
| | - Daniel Maluf
- University of Maryland, Baltimore, Baltimore, MD, United States
| | - Chris Freise
- University of California, San Francisco, San Francisco, CA, United States
| | - Nancy Ascher
- University of California, San Francisco, San Francisco, CA, United States
| | - John Roberts
- University of California, San Francisco, San Francisco, CA, United States
| | - Garrett Roll
- University of California, San Francisco, San Francisco, CA, United States
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9
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Widmer J, Eden J, Carvalho MF, Dutkowski P, Schlegel A. Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain? J Clin Med 2022; 11:5218. [PMID: 36079148 PMCID: PMC9457017 DOI: 10.3390/jcm11175218] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 08/30/2022] [Indexed: 11/28/2022] Open
Abstract
Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques-dissimilar to SCS-mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.
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Affiliation(s)
- Jeannette Widmer
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, 50139 Florence, Italy
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
| | - Andrea Schlegel
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zürich, Switzerland
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
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10
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Karangwa SA, Adelmeijer J, Burgerhof JGM, Lisman T, de Meijer VE, de Kleine RH, Reyntjens KMEM, van den Berg AP, Porte RJ, de Boer MT. Controlled DCD Liver Transplantation Is Not Associated With Increased Hyperfibrinolysis and Blood Loss After Graft Reperfusion. Transplantation 2022; 106:308-317. [PMID: 33606482 DOI: 10.1097/tp.0000000000003698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The specific effect of donation after circulatory death (DCD) liver grafts on fibrinolysis, blood loss, and transfusion requirements after graft reperfusion is not well known. The aim of this study was to determine whether transplantation of controlled DCD livers is associated with an elevated risk of hyperfibrinolysis, increased blood loss, and higher transfusion requirements upon graft reperfusion, compared with livers donated after brain death (DBD). METHODS A retrospective single-center analysis of all adult recipients of primary liver transplantation between 2000 and 2019 was performed (total cohort n = 628). Propensity score matching was used to balance baseline characteristics for DCD and DBD liver recipients (propensity score matching cohort n = 218). Intraoperative and postoperative hemostatic variables between DCD and DBD liver recipients were subsequently compared. Additionally, in vitro plasma analyses were performed to compare the intraoperative fibrinolytic state upon reperfusion. RESULTS No significant differences in median (interquartile range) postreperfusion blood loss (1.2 L [0.5-2.2] versus 1.3 L [0.6-2.2]; P = 0.62), red blood cell transfusion (2 units [0-4] versus 1.1 units [0-3]; P = 0.21), or fresh frozen plasma transfusion requirements (0 unit [0-2.2] versus 0 unit [0-0.9]; P = 0.11) were seen in DCD compared with DBD recipients, respectively. Furthermore, plasma fibrinolytic potential was similar in both groups. CONCLUSIONS Transplantation of controlled DCD liver grafts does not result in higher intraoperative blood loss or more transfusion requirements, compared with DBD liver transplantation. In accordance with this, no evidence for increased hyperfibrinolysis upon reperfusion in DCD compared with DBD liver grafts was found.
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Affiliation(s)
- Shanice A Karangwa
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, Section of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jelle Adelmeijer
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Johannes G M Burgerhof
- Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Vincent E de Meijer
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, Section of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ruben H de Kleine
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, Section of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Koen M E M Reyntjens
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Aad P van den Berg
- Department of Gastroenterology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robert J Porte
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, Section of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Marieke T de Boer
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, Section of HPB Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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11
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Meier RPH, Kelly Y, Yamaguchi S, Braun HJ, Lunow-Luke T, Adelmann D, Niemann C, Maluf DG, Dietch ZC, Stock PG, Kang SM, Feng S, Posselt AM, Gardner JM, Syed SM, Hirose R, Freise CE, Ascher NL, Roberts JP, Roll GR. Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation. Front Surg 2022; 8:808733. [PMID: 35071316 PMCID: PMC8766343 DOI: 10.3389/fsurg.2021.808733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/09/2021] [Indexed: 11/17/2022] Open
Abstract
Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally. Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems. Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not. Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.
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Affiliation(s)
- Raphael P. H. Meier
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Surgery, University of Maryland, Baltimore, MD, United States
| | - Yvonne Kelly
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Seiji Yamaguchi
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Hillary J. Braun
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Tyler Lunow-Luke
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Dieter Adelmann
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Anesthesia, University of California, San Francisco, San Francisco, CA, United States
| | - Claus Niemann
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Department of Anesthesia, University of California, San Francisco, San Francisco, CA, United States
| | - Daniel G. Maluf
- Department of Surgery, University of Maryland, Baltimore, MD, United States
| | - Zachary C. Dietch
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Peter G. Stock
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Sang-Mo Kang
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Sandy Feng
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Andrew M. Posselt
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - James M. Gardner
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Shareef M. Syed
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Chris E. Freise
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Nancy L. Ascher
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
| | - Garrett R. Roll
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
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12
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Schlegel A, Foley DP, Savier E, Flores Carvalho M, De Carlis L, Heaton N, Taner CB. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation. Transplantation 2021; 105:1892-1903. [PMID: 34416750 DOI: 10.1097/tp.0000000000003825] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.
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Affiliation(s)
- Andrea Schlegel
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, United Kingdom
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - David P Foley
- University of Wisconsin School of Medicine and Public Health, William S. Middleton VA Medical Center, Madison, WI
| | - Eric Savier
- Department of Hepatobiliary Surgery and Liver Transplantation, Sorbonne Université Pitié-Salpêtrière Hospital, Paris, France
| | - Mauricio Flores Carvalho
- Hepatobiliary Unit, Department of Clinical and Experimental Medicine, University of Florence, AOU Careggi, Florence, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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13
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Haque O, Raigani S, Rosales I, Carroll C, Coe TM, Baptista S, Yeh H, Uygun K, Delmonico FL, Markmann JF. Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury. Front Surg 2021; 8:644859. [PMID: 34222314 PMCID: PMC8245781 DOI: 10.3389/fsurg.2021.644859] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 05/24/2021] [Indexed: 12/29/2022] Open
Abstract
Background: A major limitation in expanding the use of donation after circulatory death (DCD) livers in transplantation is the increased risk of graft failure secondary to ischemic cholangiopathy. Warm ischemia causes thrombosis and injury to the peribiliary vascular plexus (PVP), which is supplied by branches of the hepatic artery, causing higher rates of biliary complications in DCD allografts. Aims/Objectives: We aimed to recondition discarded DCD livers with tissue plasminogen activator (tPA) while on normothermic machine perfusion (NMP) to improve PVP blood flow and reduce biliary injury. Methods: Five discarded DCD human livers underwent 12 h of NMP. Plasminogen was circulated in the base perfusate prior to initiation of perfusion and 1 mg/kg of tPA was administered through the hepatic artery at T = 0.5 h. Two livers were split prior to perfusion (S1, S2), with tPA administered in one lobe, while the other served as a control. The remaining three whole livers (W1-W3) were compared to seven DCD control liver perfusions (C1-C7) with similar hepatocellular and biliary viability criteria. D-dimer levels were measured at T = 1 h to verify efficacy of tPA. Lactate, total bile production, bile pH, and difference in biliary injury scores before and after perfusion were compared between tPA and non-tPA groups using unpaired, Mann-Whitney tests. Results: Average weight-adjusted D-dimer levels were higher in tPA livers in the split and whole-liver model, verifying drug function. There were no differences in perfusion hepatic artery resistance, portal vein resistance, and arterial lactate between tPA livers and non-tPA livers in both the split and whole-liver model. However, when comparing biliary injury between hepatocellular and biliary non-viable whole livers, tPA livers had significantly lower PVP injury scores (0.67 vs. 2.0) and mural stroma (MS) injury scores (1.3 vs. 2.7). Conclusion: This study demonstrates that administration of tPA into DCD livers during NMP can reduce PVP and MS injury. Further studies are necessary to assess the effect of tPA administration on long term biliary complications.
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Affiliation(s)
- Omar Haque
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Siavash Raigani
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Ivy Rosales
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Cailah Carroll
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Taylor M Coe
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Sofia Baptista
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States
| | - Heidi Yeh
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Korkut Uygun
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Shriners Hospitals for Children, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
| | - Francis L Delmonico
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States.,New England Donor Services (NEDS), Waltham, MA, United States
| | - James F Markmann
- Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, United States.,Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, United States.,Harvard Medical School, Boston, MA, United States
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14
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Haque OJ, Roth EM, Fleishman A, Eckhoff DE, Khwaja K. Long-Term Outcomes of Early Experience in Donation After Circulatory Death Liver Transplantation: Outcomes at 10 Years. Ann Transplant 2021; 26:e930243. [PMID: 33875633 PMCID: PMC8067669 DOI: 10.12659/aot.930243] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Donation after circulatory death (DCD) livers remain an underutilized pool of transplantable organs due to concerns of inferior long-term patient survival (PS) and graft survival (GS), which factors greatly into clinician decision-making and patient expectations. MATERIAL AND METHODS This retrospective study used SRTR data to assess 33 429 deceased-donor liver transplants (LT) and compared outcomes between DCD and donation after brain death (DBD) LT recipients in the United States. Data were collected from 2002 to 2008 to obtain 10 years of follow-up (2012-2018) in the era of MELD implementation. Propensity scores for donor type (DCD vs DBD) were estimated using logistic regression, and the association of donor type with 10-year outcomes was evaluated after adjustment using stabilized inverse probability of treatment weights. RESULTS After adjusting for confounders, patient survival for DBD recipients at 10 years was 60.7% versus 57.5% for DCD recipients (P=0.24). Incorporating retransplants, 10-year adjusted patient survival was 60.2% for DBD recipients versus 55.5% for DCD recipients (P=0.07). Adjusted 10-year graft survival for DBD recipients was 56.4% versus 45.4% for DCD recipients (P<0.001). Surprisingly, however, 1 year after LT, DBD and DCD graft failure rates converged to 7.5% over the remaining 9 years. CONCLUSIONS These data reveal inferior 10-year DCD graft survival, but only in the first year after LT, and similar 10-year patient survival in DCD LT recipients compared to DBD recipients. Our results show the stability and longevity of DCD grafts, which should encourage the increased utilization of these livers for transplantation.
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Affiliation(s)
- Omar J Haque
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Eve M Roth
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Aaron Fleishman
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Devin E Eckhoff
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
| | - Khalid Khwaja
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Harvard Medical School, Boston, MA, USA
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15
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Singh N, Helfrich K, Mumtaz K, Washburn K, Logan A, Black S, Schenk A, Limkemann A, Alebrahim M, El-Hinnawi A. Donation After Circulatory Death Yields Survival Rates Similar to Donation After Brain Death Liver Transplant, Which Effectively Expands the Donor Pool. EXP CLIN TRANSPLANT 2021; 19:771-778. [PMID: 33877039 DOI: 10.6002/ect.2021.0013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Liver allograft shortage has necessitated greater use of donations after circulatory death. Limited data are available to compare recipients' health care utilization for donation after circulatory death versus brain death. MATERIALS AND METHODS Liver transplant data for our center from November 2016 until May 2019 were obtained (208 donations after brain death and 39 after circulatory death). We excluded patients <18 years old and multiorgan transplants; for cost data only, we also excluded retransplants. Primary outcome was recipients' health care utilization in donation after circulatory death versus brain death and included index admission length of stay, readmissions, and charges from transplant to 6 months. Secondary outcomes were patient and graft survival. RESULTS Donors from circulatory death were younger than donors from brain death (median age 32 vs 40 years; P < .01). Recipient body mass index (31.23 vs 29.38 kg/m2), Model for End-Stage Liver Disease score (17 vs 19), portal vein thrombosis (15.8% vs 18.0%), length of stay (7 vs 8 days), and 30-, 90-, and 180-day posttransplant index admissions were not significantly different. Charges for index admission were equivalent for donation after circulatory death ($370771) and brain death ($374272) (P = .01). Charges for readmissions at 30 and 180 days were not significantly different (P = .80 and P = .19, respectively). Rates for graft failure (10.3% vs 4.8%; P = .08) and recipient death (10.3% vs 3.8%; P = .17) at 6 months posttransplant were similar. CONCLUSIONS Donation after circulatory death versus brain death liver transplant recipients had similar lengths of stay and equivalent index admission charges. Graft and patient survival and charges from transplant to 6 months were similar. Donation after circulatory death liver allografts provide a safe, costequivalent donor pool expansion after careful donorrecipient selection.
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Affiliation(s)
- Navdeep Singh
- From the Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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16
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Hobeika MJ, Saharia A, Mobley CM, Menser T, Nguyen DT, Graviss EA, McMillan RR, Podder H, Nolte Fong JV, Jones SL, Yi SG, Elshawwaf M, Gaber AO, Ghobrial RM. Donation after circulatory death liver transplantation: An in-depth analysis and propensity score-matched comparison. Clin Transplant 2021; 35:e14304. [PMID: 33792971 DOI: 10.1111/ctr.14304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 03/14/2021] [Accepted: 03/24/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Careful donor-recipient matching and reduced ischemia times have improved outcomes following donation after circulatory death (DCD) liver transplantation (LT). This study examines a single-center experience with DCD LT including high-acuity and hospitalized recipients. METHODS DCD LT outcomes were compared to a propensity score-matched (PSM) donation after brain death (DBD) LT cohort (1:4); 32 DCD LT patients and 128 PSM DBD LT patients transplanted from 2008 to 2018 were included. Analyses included Kaplan-Meier estimates and Cox proportional hazards models examining patient and graft survival. RESULTS Median MELD score in the DCD LT cohort was 22, with median MELD of 27 for DCD LT recipients with decompensated cirrhosis. No difference in mortality or graft loss was found (p < .05) between DCD LT and PSM DBD LT at 3 years post-transplant, nor was DCD an independent risk factor for patient or graft survival. Post-LT severe acute kidney injury was similar in both groups. Ischemic-type biliary lesions (ITBL) occurred in 6.3% (n = 2) of DCD LT recipients, resulting in 1 graft loss and 1 death. CONCLUSION This study supports that DCD LT outcomes can be similar to DBD LT, with a low rate of ITBL, in a cohort including high-acuity recipients. Strict donor selection criteria, ischemia time minimization, and avoiding futile donor/recipient combinations are essential considerations.
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Affiliation(s)
- Mark J Hobeika
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA.,Center for Outcomes Research, Houston Methodist, Houston, Texas, USA
| | - Ashish Saharia
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA
| | - Constance M Mobley
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA
| | - Terri Menser
- Center for Outcomes Research, Houston Methodist, Houston, Texas, USA.,Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York, USA
| | - Duc T Nguyen
- Department of Pathology and Genomic Medicine, Houston Methodist, Houston, Texas, USA
| | - Edward A Graviss
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Pathology and Genomic Medicine, Houston Methodist, Houston, Texas, USA
| | - Robert R McMillan
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA
| | - Hemangshu Podder
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA
| | - Joy V Nolte Fong
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA
| | - Stephen L Jones
- Department of Surgery, Weill Cornell Medical College, New York, New York, USA.,Center for Outcomes Research, Houston Methodist, Houston, Texas, USA
| | - Stephanie G Yi
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA
| | - Mahmoud Elshawwaf
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA
| | - Ahmed O Gaber
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA
| | - Rafik M Ghobrial
- Department of Surgery, J.C. Walter, Jr. Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist, Houston, Texas, USA.,Department of Surgery, Weill Cornell Medical College, New York, New York, USA
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17
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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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18
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Kubal C, Roll GR, Ekser B, Muiesan P. Donation after circulatory death liver transplantation: What are the limits for an acceptable DCD graft? Int J Surg 2020; 82S:36-43. [PMID: 32389812 DOI: 10.1016/j.ijsu.2020.04.064] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/17/2020] [Accepted: 04/27/2020] [Indexed: 01/06/2023]
Abstract
The utilization of donation after circulatory death (DCD) livers has been growing over the last decade. In large-volume centers, survival outcomes have improved and are comparable to outcomes with brain death donor (DBD) liver transplantation (LT). The relatively concentrated success with DCD LT demonstrated by high-volume transplant centers has rekindled international enthusiasm. The combination of increasing expertise in DCD LT and ongoing shortage in transplantable organs has promoted expansion of the DCD donor pool with regards to donor age, body mass index and donor warm ischemia time. In this review, we focused on the practice patterns in DCD liver graft utilization in the last decade, along with the possibilities for further expansion of DCD liver graft utilization and new technologies, such as machine perfusion.
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Affiliation(s)
- ChandrashekharA Kubal
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Garrett R Roll
- Department of Surgery, Division of Transplantation, University of California San Francisco, San Francisco, CA, USA.
| | - Burcin Ekser
- Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
| | - Paolo Muiesan
- The Liver Unit, Queen Elizabeth University Hospital, Birmingham, United Kingdom.
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19
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Little CJ, Dick AAS, Perkins JD, Hsu EK, Reyes JD. Livers From Pediatric Donation After Circulatory Death Donors Represent a Viable and Underutilized Source of Allograft. Liver Transpl 2020; 26:1138-1153. [PMID: 32403205 DOI: 10.1002/lt.25795] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 04/16/2020] [Accepted: 05/04/2020] [Indexed: 01/13/2023]
Abstract
Despite increased numbers of donation after circulatory death (DCD) donors, pediatric DCD livers are underused. To investigate possible reasons for this discrepancy, we conducted a retrospective cohort study using 2 data sets from the Organ Procurement and Transplantation Network for all deceased liver donors and for all recipients of DCD liver transplants from March 8, 1993, to June 30, 2018. Pediatric (0-12 years) and adolescent (13-17 years) DCD donors were compared with those aged 18-40 years. We found that pediatric DCD allografts are recovered at a significantly lower rate than from 18-to-40-year-old donors (27.3% versus 56.3%; P < 0.001). However, once recovered, these organs are transplanted at a similar rate to those from the 18-to-40-year-old donor cohort (74.7% versus 74.2%). Significantly more pediatric DCD livers (odds ratio [OR], 3.75; confidence interval [CI], 3.14-4.47) were not recovered compared with adult organs, which were most commonly not recovered due to organ quality (10.2% versus 7.1%; P < 0.001). The 10-year relative risks (RRs) for graft failure and patient death were similar between pediatric and adult DCD donors, with adolescent DCD livers demonstrating improved outcomes. DCD livers transplanted into pediatric donors were protective against graft failure (RR, 0.46; 95% confidence interval [CI], 0.21-0.99) and patient death (RR, 0.16; 95% CI, 0.04-0.69). In conclusion, despite lower rates of recovery, pediatric DCD livers represent a viable organ source for certain adults and children.
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Affiliation(s)
| | - Andre A S Dick
- Division of Transplantation, University of Washington Medical Center, Seattle, WA.,Seattle Children's Hospital, Section of Pediatric Transplantation, Seattle, WA
| | - James D Perkins
- Division of Transplantation, University of Washington Medical Center, Seattle, WA
| | - Evelyn K Hsu
- Division of Gastroenterology, Department of Pediatrics, University of Washington Medical Center, Seattle, WA
| | - Jorge D Reyes
- Division of Transplantation, University of Washington Medical Center, Seattle, WA.,Seattle Children's Hospital, Section of Pediatric Transplantation, Seattle, WA
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20
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Bath NM, Leverson G, Al-Adra D, D’Alessandro A, Mezrich J, Foley DP. Microsteatosis in Livers From Donation After Circulatory Death Donors Is Associated With Inferior Outcomes Following Liver Transplantation. Liver Transpl 2020; 26:1127-1137. [PMID: 32453905 PMCID: PMC8860344 DOI: 10.1002/lt.25803] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/20/2020] [Accepted: 04/05/2020] [Indexed: 12/20/2022]
Abstract
The acceptable threshold remains unknown for the percentage of macrosteatosis (MaS) and microsteatosis (MiS) to yield optimal outcomes after donation after circulatory death (DCD) liver transplantation (LT). The purpose of this analysis was to determine the impact of donor liver MaS and MiS on DCD LT outcomes. Using the Organ Procurement and Transplantation Network database, we analyzed pretransplant biopsy results from adult, solitary, DCD livers transplanted between January 1, 2006, and December 31, 2017. Kaplan-Meier analysis was used to assess graft and patient survival based on MaS and MiS severity. MiS was divided into the groups MiS ≤10% and >10%. MaS was divided into the groups MaS ≤15% and >15%. Of 7757 recovered DCD livers, 11.4% (n = 885) were biopsied and transplanted. Patients who received DCD livers with MaS >15% had significantly worse patient survival (P < 0.04), and those with MiS >10% demonstrated inferior graft and patient survival (P < 0.02). In multivariate analyses including known risk factors, both MaS >15% and MiS >10% were associated with increased risk of graft failure and patient mortality (P < 0.03). Recipient and donor age >60 years were also associated with increased risk of graft failure and patient death. This analysis demonstrates that MaS >15% and MiS >10% are additional risk factors for graft loss and patient mortality in DCD LT.
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Affiliation(s)
- Natalie M. Bath
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Glen Leverson
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - David Al-Adra
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Anthony D’Alessandro
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Joshua Mezrich
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - David P. Foley
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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21
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Yamada S, Miyagi S, Hara Y, Kakizaki Y, Sasajima H, Mitsui K, Fujimori K, Unno M, Kamei T, Goto M. Effects of Short-Term Normothermic and Subnormothermic Perfusion After Cold Preservation on Liver Transplantation From Donors After Cardiac Death. Transplant Proc 2020; 52:1639-1642. [PMID: 32471629 DOI: 10.1016/j.transproceed.2020.01.147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 01/22/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Liver transplantation from donors after cardiac death (DCD) could increase the pool of organs. We previously reported that oxygenated subnormothermic (20°C-25°C) ex vivo liver perfusion (SELP) improved the graft viability in rats. This study aimed to compare the effectiveness of SELP and normothermic (37°C) ex vivo liver perfusion (NELP) after cold storage (CS) in DCD liver grafts. METHODS Male Wistar rats were used, and grafts were retrieved 30 minutes after cardiac arrest. We performed oxygenated NELP and SELP with a Krebs-Henseleit buffer for different time points and durations: Group 0, donation performed from heart-beating donors (control); Group 1 (DCD group), donation performed from DCD donors with no treatments; Group 2, NELP performed before CS (30 minutes); Group 3, NELP performed after CS (30 minutes); Group 4, SELP performed after CS (30 minutes); Group 5, SELP performed after CS (60 minutes); and Group 6, SELP performed after CS (90 minutes). After 15 minutes of incubation at room temperature, the grafts were reperfused under normothermic conditions for 60 minutes as a model of liver transplantation. RESULTS No significant differences in body and liver weight were observed between all groups. In the SELP after CS groups, even 30 minutes of perfusion improved bile production, tumor necrosis factor-α, and interleukin-1β significantly compared with the DCD group (P < .05), comparable with NELP groups. CONCLUSION SELP rescued DCD livers from ischemia-reperfusion injury the same as the normothermic perfusion before or after CS groups. SELP after CS is more convenient than normothermic perfusion; hence, this technique may increase the organ pool.
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Affiliation(s)
- Shuhei Yamada
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shigehito Miyagi
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Yasuyuki Hara
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yuta Kakizaki
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hideaki Sasajima
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazuhiro Mitsui
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Keisei Fujimori
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masafumi Goto
- Department of Transplantation and Regenerative Medicine, Tohoku University, Graduate School of Medicine, Sendai, Japan
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22
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Too Much, Too Little, or Just Right? The Importance of Allograft Portal Flow in Deceased Donor Liver Transplantation. Transplantation 2020; 104:770-778. [DOI: 10.1097/tp.0000000000002968] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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23
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Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma. J Clin Med 2019; 8:jcm8101692. [PMID: 31618968 PMCID: PMC6832253 DOI: 10.3390/jcm8101692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 10/05/2019] [Indexed: 02/06/2023] Open
Abstract
The major extended donor criteria (maEDC; steatosis >40%, age >65 years, and cold ischemia time >14 h) influence graft and patient outcomes after liver transplantation. Despite organ shortages, maEDC organs are often considered unsuitable for transplantation. We investigated the outcomes of maEDC organ liver transplantation in patients with hepatocellular carcinoma (HCC). Two hundred and sixty-four HCC liver transplant patients were eligible for analysis. Risk factor analysis was performed for early allograft dysfunction; primary nonfunction; 30-day and 90-day graft failure; and 30-day, 90-day, and 1-year patient mortality. One-year graft survival was higher in recipients of no-maEDC grafts. One-year patient survival did not differ between the recipients of no-maEDC and maEDC organs. The univariate and multivariate analyses revealed no association between maEDC grafts and one-year patient mortality. Graft survival differed between the recipients of no-maEDC and maEDC organs after correcting for a laboratory model of end-stage liver disease (labMELD) score with a cut-off value of 20, but patient survival did not. Patient survival did not differ between recipients who did and did not meet the Milan criteria and who received grafts with and without maEDC. Instead of being discarded, maEDC grafts may expand the organ pool for patients with HCC without impairing patient survival or recurrence-free survival.
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24
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Tschuor C, Ferrarese A, Kuemmerli C, Dutkowski P, Burra P, Clavien PA. Allocation of liver grafts worldwide - Is there a best system? J Hepatol 2019; 71:707-718. [PMID: 31199941 DOI: 10.1016/j.jhep.2019.05.025] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 05/23/2019] [Accepted: 05/27/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. The most frequent principles for allocation policies in liver transplantation are therefore criteria that rely on pre-transplant survival (sickest first policy), post-transplant survival (utility), or on their combination (benefit). However, large differences exist between centers and countries for ethical and legislative reasons. The aim of this study was to report the current worldwide practice of liver graft allocation and discuss respective advantages and disadvantages. METHODS Countries around the world that perform 95 or more deceased donor liver transplantations per year were analyzed for donation and allocation policies, as well as recipient characteristics. RESULTS Most countries use the model for end-stage liver disease (MELD) score, or variations of it, for organ allocation, while some countries opt for center-based allocation systems based on their specific requirements, and some countries combine both a MELD and center-based approach. Both the MELD and center-specific allocation systems have inherent limitations. For example, most countries or allocation systems address the limitations of the MELD system by adding extra points to recipient's laboratory scores based on clinical information. It is also clear from this study that cancer, as an indication for liver transplantation, requires special attention. CONCLUSION The sickest first policy is the most reasonable basis for the allocation of liver grafts. While MELD is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors, predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs. LAY SUMMARY An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. While the model for end-stage liver disease is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs.
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Affiliation(s)
- Christoph Tschuor
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Alberto Ferrarese
- Multivisceral Transplant Unit - Gastroenterology, Padua University Hospital, Padua, Italy
| | - Christoph Kuemmerli
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Patrizia Burra
- Multivisceral Transplant Unit - Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Pierre-Alain Clavien
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland.
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25
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Mihaylov P, Mangus R, Ekser B, Cabrales A, Timsina L, Fridell J, Lacerda M, Ghabril M, Nephew L, Chalasani N, Kubal CA. Expanding the Donor Pool With the Use of Extended Criteria Donation After Circulatory Death Livers. Liver Transpl 2019; 25:1198-1208. [PMID: 30929303 DOI: 10.1002/lt.25462] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 03/16/2019] [Indexed: 02/07/2023]
Abstract
Use of donation after circulatory death (DCD) donor livers for transplantation has remained cautious in the United States. The aim of this study was to demonstrate the expansion of a DCD liver transplantation (LT) program with the use of extended criteria donor (ECD) DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with 1 of the following factors: donor age >50 years, donor body mass index >35 kg/m2 , donor functional warm ischemia time >30 minutes, and donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush and efforts to minimize ischemia times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC), and change in DCD LT volume. Of 135 consecutive DCD LTs, 62 were ECD DCDs. In total, 24 ECD DCD LTs were performed before (era 1) and 38 after the institution of optimization protocol (era 2), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in era 2, with a significantly lower incidence of IC (5% versus 17% in era 1; P = 0.03) and better 1-year graft survival (93% versus 75% in era 1; P = 0.07). Survival outcomes for ECD DCD LT in era 2 were comparable to matched deceased donor LT. With the expansion of the DCD donor pool, the number of DCD LTs performed at our center gradually increased in era 2 to account for >20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT.
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Affiliation(s)
- Plamen Mihaylov
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Richard Mangus
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Burcin Ekser
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Arianna Cabrales
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Lava Timsina
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN
| | - Jonathan Fridell
- Transplant Division, Indiana University School of Medicine, Indianapolis, IN
| | - Marco Lacerda
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Lauren Nephew
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN
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26
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Use of Hepatitis C-Positive Liver Grafts in Hepatitis C-Negative Recipients. Dig Dis Sci 2019; 64:1110-1118. [PMID: 30560331 DOI: 10.1007/s10620-018-5404-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/27/2018] [Indexed: 12/18/2022]
Abstract
As the demand for liver transplantation continues to rise, the scarcity of liver donor grafts has led to the use of extended criteria grafts for liver transplantation in select group of patients. Hepatitis C-seropositive liver grafts have been used primarily in hepatitis C-positive recipients, with studies showing non-inferior outcomes when compared to hepatitis C-negative grafts. Studies suggest that hepatitis C serology status of the donor liver does not influence the patient or graft outcomes in the recipient. These results advocate for offering hepatitis C-positive grafts to all patients awaiting liver transplantation regardless of their hepatitis C status. However, some concerns persist regarding the ethics of potentially introducing a new infection into a patient that could progress to chronic liver disease following liver transplantation. The recent approval of direct-acting antiviral therapy offers a solution to this dilemma, as it has changed the landscape of hepatitis C management by making it a curable disease. In this review, we shall discuss the current evidence regarding the use of hepatitis C-seropositive donor grafts in hepatitis C-positive and hepatitis C-negative patients.
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27
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Pavel MC, Reyner E, Molina V, Garcia R, Ruiz A, Roque R, Diaz A, Fuster J, Garcia-Valdecasas JC. Evolution Under Normothermic Machine Perfusion of Type 2 Donation After Cardiac Death Livers Discarded as Nontransplantable. J Surg Res 2019; 235:383-394. [DOI: 10.1016/j.jss.2018.09.066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 09/05/2018] [Accepted: 09/20/2018] [Indexed: 02/06/2023]
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28
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Pardo F, Pons JA, Castells L, Colmenero J, Gómez MÁ, Lladó L, Pérez B, Prieto M, Briceño J. VI consensus document by the Spanish Liver Transplantation Society. Cir Esp 2019; 96:326-341. [PMID: 29776591 DOI: 10.1016/j.ciresp.2017.12.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 11/19/2017] [Accepted: 12/13/2017] [Indexed: 12/20/2022]
Abstract
The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below.
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Affiliation(s)
- Fernando Pardo
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Clínica Universitaria de Navarra, Pamplona, España
| | - José Antonio Pons
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Virgen de la Arrixaca, Murcia, España
| | - Lluís Castells
- Unidad de Trasplante Hepático, Hospital Vall d'Hebron, Barcelona, España
| | - Jordi Colmenero
- Unidad de Trasplante Hepático, Hospital Clínic, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Trasplante Hepático, Hospital Virgen del Rocío, Sevilla, España
| | - Laura Lladó
- Unidad de Trasplante Hepático, Hospital de Bellvitge, Barcelona, España
| | - Baltasar Pérez
- Unidad de Trasplante Hepático, Hospital Universitario de Valladolid, Valladolid, España
| | - Martín Prieto
- Unidad de Trasplante Hepático, Hospital Universitario La Fe, Valencia, España
| | - Javier Briceño
- Comité Científico de la Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Universitario Reina Sofía, Córdoba, España.
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29
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Capelli R, Allard M, Ciacio O, Pittau G, Golse N, Vibert E, Sa Cunha A, Castaing D, Cherqui D, Adam R. Late hepaticartery thrombosis after liver transplantation: which strategy? A single‐center retrospective study. Transpl Int 2019; 32:473-480. [DOI: 10.1111/tri.13394] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 10/22/2018] [Accepted: 12/12/2018] [Indexed: 01/10/2023]
Affiliation(s)
- Rafaela Capelli
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
| | - Marc‐Antoine Allard
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Unités Mixtes de Recherche en Santé 1193 Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
| | - Oriana Ciacio
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
| | - Gabriella Pittau
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
| | - Nicolas Golse
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Unités Mixtes de Recherche en Santé 1193 Villejuif France
| | - Eric Vibert
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Unités Mixtes de Recherche en Santé 1193 Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
| | - Antonio Sa Cunha
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
| | - Denis Castaing
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Unités Mixtes de Recherche en Santé 1193 Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
| | - Daniel Cherqui
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
| | - René Adam
- Centre Hépato‐Biliaire AP‐HP Hôpital Paul Brousse Villejuif France
- Faculté de Médecine Université Paris‐Sud Le Kremlin‐Bicêtre France
- Unités Mixtes de Recherche en Santé 985 INSERM Villejuif France
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30
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Jayant K, Reccia I, Virdis F, Shapiro AMJ. Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death. J Clin Med 2018; 7:425. [PMID: 30413051 PMCID: PMC6262573 DOI: 10.3390/jcm7110425] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/02/2018] [Accepted: 11/06/2018] [Indexed: 02/06/2023] Open
Abstract
AIM The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. METHODS An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. RESULTS A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). CONCLUSIONS To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.
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Affiliation(s)
- Kumar Jayant
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | - Isabella Reccia
- Department of Surgery and Cancer, Imperial College London, London W12 OHS, UK.
| | | | - A M James Shapiro
- Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada.
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Pavel MC, Reyner E, Fuster J, Garcia-Valdecasas JC. Trasplante hepático con injerto de donante en asistolia tipo 2 con perfusión regional normotérmica y máquina de perfusión normotérmica. Cir Esp 2018; 96:508-513. [DOI: 10.1016/j.ciresp.2018.06.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/06/2018] [Accepted: 06/21/2018] [Indexed: 01/14/2023]
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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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Kollmann D, Sapisochin G, Goldaracena N, Hansen BE, Rajakumar R, Selzner N, Bhat M, McCluskey S, Cattral MS, Greig PD, Lilly L, McGilvray ID, Ghanekar A, Grant DR, Selzner M. Expanding the donor pool: Donation after circulatory death and living liver donation do not compromise the results of liver transplantation. Liver Transpl 2018; 24:779-789. [PMID: 29604237 PMCID: PMC6099346 DOI: 10.1002/lt.25068] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 02/23/2018] [Accepted: 03/13/2018] [Indexed: 12/12/2022]
Abstract
Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1-, 3-, and 5-year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1-, 3-, and 5-year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779-789 2018 AASLD.
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Affiliation(s)
| | | | | | - Bettina E. Hansen
- Toronto Centre for Liver DiseaseToronto General HospitalOnatrioCanada
- Institute of Health Policy, Management and EvaluationUniversity of TorontoTorontoOntarioCanada
| | | | - Nazia Selzner
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | - Mamatha Bhat
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | - Stuart McCluskey
- Department of MedicineMulti‐Organ Transplant ProgramToronto General HospitalOnatrioCanada
| | | | - Paul D. Greig
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - Les Lilly
- Department of Anesthesia and Pain ManagementToronto General HospitalOnatrioCanada
| | | | - Anand Ghanekar
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - David R. Grant
- Department of SurgeryToronto General HospitalOnatrioCanada
| | - Markus Selzner
- Department of SurgeryToronto General HospitalOnatrioCanada
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Pardo F, Pons JA, Castells L, Colmenero J, Gómez MÁ, Lladó L, Pérez B, Prieto M, Briceño J. VI consensus document by the Spanish Liver Transplantation Society. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:406-421. [PMID: 29866511 DOI: 10.1016/j.gastrohep.2018.05.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 02/19/2018] [Accepted: 05/14/2018] [Indexed: 12/13/2022]
Abstract
The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below.
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Affiliation(s)
- Fernando Pardo
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Clínica Universitaria de Navarra, Pamplona, España
| | - José Antonio Pons
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Virgen de la Arrixaca, Murcia, España
| | - Lluís Castells
- Unidad de Trasplante Hepático, Hospital Vall d'Hebron, Barcelona, España
| | - Jordi Colmenero
- Unidad de Trasplante Hepático, Hospital Clínic, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Trasplante Hepático, Hospital Virgen del Rocío, Sevilla, España
| | - Laura Lladó
- Unidad de Trasplante Hepático, Hospital de Bellvitge, Barcelona, España
| | - Baltasar Pérez
- Unidad de Trasplante Hepático, Hospital Universitario de Valladolid, Valladolid, España
| | - Martín Prieto
- Unidad de Trasplante Hepático, Hospital Universitario La Fe, Valencia, España
| | - Javier Briceño
- Comité Científico de la Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Universitario Reina Sofía, Córdoba, España.
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35
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Elnaggar AS, Guarrera JV. The Marginal Liver Donor and Organ Preservation Strategies. LIVER ANESTHESIOLOGY AND CRITICAL CARE MEDICINE 2018:207-220. [DOI: 10.1007/978-3-319-64298-7_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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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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37
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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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38
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Croome KP, Lee DD, Nguyen JH, Keaveny AP, Taner CB. Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores. Am J Transplant 2017; 17:2420-2427. [PMID: 28556380 DOI: 10.1111/ajt.14383] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/04/2017] [Accepted: 05/11/2017] [Indexed: 01/25/2023]
Abstract
Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.
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Affiliation(s)
- K P Croome
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - D D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - J H Nguyen
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - A P Keaveny
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - C B Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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Ezekian B, Mulvihill MS, Freischlag K, Yerokun BA, Davis RP, Hartwig MG, Knechtle SJ, Barbas AS. Elevated HbA1c in donor organs from patients without a diagnosis of diabetes portends worse liver allograft survival. Clin Transplant 2017; 31. [PMID: 28667782 DOI: 10.1111/ctr.13047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/28/2017] [Indexed: 11/26/2022]
Abstract
Recipients of liver allografts from diabetic donors have decreased graft survival. However, limited data exist on the effects of donor HbA1c. We hypothesized that allografts from nondiabetic donors with elevated HbA1c would be associated with decreased survival. Liver transplant recipients from the UNOS database from nondiabetic donors were stratified into two groups: euglycemic (HbA1c<6.5) and hyperglycemic (HbA1c≥6.5). Propensity score matching (10:1) was used to adjust for donor and recipient characteristics. Kaplan-Meier analysis was used to assess survival. Donors of hyperglycemic allografts were older (49 vs 36, P<.001), were more likely to be non-white, had a higher BMI (29.8 vs 26.2, P<.001), were more likely to engage in heavy cigarette use (1.5% vs 1.3%, P=.004), had higher serum creatinine levels (1.3 vs 1.0, P=.002), and were more likely to be an expanded-criteria donor (35.8% vs 14.4%, P<.001). After propensity matching to account for these differences, allograft survival was significantly decreased in the recipients of hyperglycemic allografts (P=.049), and patient survival showed a trend toward reduction (P=.082). These findings suggest that HbA1c may be a simple and inexpensive test with potential utility for better organ risk stratification.
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Affiliation(s)
- Brian Ezekian
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Kyle Freischlag
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | | | - Robert P Davis
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Matthew G Hartwig
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Stuart J Knechtle
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
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40
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Henson JB, Patel YA, King LY, Zheng J, Chow SC, Muir AJ. Outcomes of liver retransplantation in patients with primary sclerosing cholangitis. Liver Transpl 2017; 23:769-780. [PMID: 28027592 PMCID: PMC5865072 DOI: 10.1002/lt.24703] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 12/08/2016] [Indexed: 01/13/2023]
Abstract
Liver retransplantation in patients with primary sclerosing cholangitis (PSC) has not been well studied. The aims of this study were to characterize patients with PSC listed for and undergoing retransplantation and to describe the outcomes in these patients. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was used to identify all primary liver transplantations and subsequent relistings and first retransplantations in adults with PSC between 1987 and 2015. A total of 5080 adults underwent primary transplantation for PSC during this period, and of the 1803 who experienced graft failure (GF), 762 were relisted, and 636 underwent retransplantation. Younger patients and patients with GF due to vascular thrombosis or biliary complications were more likely to be relisted, whereas those with Medicaid insurance or GF due to infection were less likely. Both 5-year graft and patient survival after retransplantation were inferior to primary transplantation (P < 0.001). Five-year survival after retransplantation for disease recurrence (REC), however, was similar to primary transplantation (graft survival, P = 0.45; patient survival, P = 0.09) and superior to other indications for retransplantation (graft and patient survival, P < 0.001). On multivariate analysis, mechanical ventilation, creatinine, bilirubin, albumin, advanced donor age, and a living donor were associated with poorer outcomes after retransplantation. In conclusion, although survival after liver retransplantation in patients with PSC was overall inferior to primary transplantation, outcomes after retransplantation for PSC REC were similar to primary transplantation at 5 years. Retransplantation may therefore represent a treatment option with the potential for excellent outcomes in patients with REC of PSC in the appropriate clinical circumstances. Liver Transplantation 23 769-780 2017 AASLD.
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Affiliation(s)
| | - Yuval A. Patel
- Division of Gastroenterology, Department of Medicine, Durham, NC
| | - Lindsay Y. King
- Division of Gastroenterology, Department of Medicine, Durham, NC
| | | | - Shein-Chung Chow
- Department of Biostatistics, Durham, NC,Duke Clinical Research Institute, Durham, NC
| | - Andrew J. Muir
- Division of Gastroenterology, Department of Medicine, Durham, NC,Duke Clinical Research Institute, Durham, NC
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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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42
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 322] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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Croome KP, Lee DD, Perry DK, Burns JM, Nguyen JH, Keaveny AP, Taner CB. Comparison of longterm outcomes and quality of life in recipients of donation after cardiac death liver grafts with a propensity-matched cohort. Liver Transpl 2017; 23:342-351. [PMID: 28027600 DOI: 10.1002/lt.24713] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 12/10/2016] [Indexed: 12/12/2022]
Abstract
The use of liver grafts from donation after cardiac death (DCD) has been limited due to the increased rate of graft failure, mostly related to ischemic cholangiopathy (IC). It is our hypothesis that longterm outcomes and quality of life (QOL) similar to patients undergoing liver transplantation (LT) with donation after brain death (DBD) can be achieved. Clinical outcomes of all patients undergoing DCD LT (n = 300) between 1998 and 2015 were compared with a propensity score-matched cohort of patients undergoing DBD LT (n = 300). Patients were contacted for a follow-up questionnaire and short-form (SF)-12 QOL Survey administration. Median follow-up was >5 years. Graft survival at 1-, 3-, and 5-years was 83.8%, 75.5%, and 70.1% in the DCD LT group and 88.4%, 80.3%, and 73.9% in the DBD LT group (P = 0.27). Patient survival at 1-, 3-, and 5-years was 92.3%, 86.1%, and 80.3% in the DCD LT group and 92.3%, 85.1%, and 79.5% in the DBD LT group (P = 0.81). IC developed in 11.7% and 2% of patients in the DCD LT group and DBD LT group, respectively (P < 0.001). DCD LT recipients who developed IC had inferior graft survival compared with both the DCD non-IC group (P < 0.001) and the DBD LT group (P < 0.001); no difference in graft survival was observed between the DCD non-IC group and the DBD LT group (P = 0.50). Physical and Mental Composite Scores on the SF-12 QOL questionnaire were similar between the DCD LT and DBD LT groups (44.0 versus 45.4; P = 0.34 and 51.9 versus 52.2; P = 0.83), respectively. Similar longterm survival and QOL scores can be achieved between DCD LT and DBD LT. Prevention of IC in DCD LT yields excellent graft and patient survival with virtually no difference compared with DBD LT. Liver Transplantation 23 342-351 2017 AASLD.
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Affiliation(s)
| | - David D Lee
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Dana K Perry
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Justin M Burns
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Justin H Nguyen
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | | | - C Burcin Taner
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
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44
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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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45
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Does Donation After Cardiac Death Utilization Adversely Affect Hepatocellular Cancer Survival? Transplantation 2016; 100:1916-24. [DOI: 10.1097/tp.0000000000001150] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Scalea JR, Redfield RR, Foley DP. Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers. Liver Transpl 2016; 22:1197-204. [PMID: 27314220 DOI: 10.1002/lt.24494] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 06/03/2016] [Indexed: 02/06/2023]
Abstract
Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation from donation after brain death (DBD) donors. We hypothesized that carefully selected, underutilized DCD livers recovered from younger donors have excellent outcomes. We performed a retrospective study of the United Network for Organ Sharing database to determine graft survivals for patients who received liver transplants from DBD donors of age ≥ 60 years, DBD donors < 60 years, and DCD donors < 50 years of age. Between January 2002 and December 2014, 52,271 liver transplants were performed in the United States. Of these, 41,181 (78.8%) underwent transplantation with livers from DBD donors of age < 60 years, 8905 (17.0%) from DBD donors ≥ 60 years old, and 2195 (4.2%) livers from DCD donors < 50 years of age. DCD livers of age < 50 years with < 6 hours of cold ischemia time (CIT) had superior graft survival when compared with DBD livers ≥ age 60 years (P < 0.001). In 2014, there were 133 discarded DCD livers; of these, 111 (83.4%) were from donors < age 50 years old. Young DCD donor livers (age < 50 years old) with short CITs yield results better than that seen with DBD livers > 60 years old. Careful donor organ and recipient selection can lead to excellent results, despite previous reports suggesting otherwise. Increased acceptance of these DCD livers would lead to shorter wait list times and increased national liver transplant rates. Liver Transplantation 22 1197-1204 2016 AASLD.
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Affiliation(s)
- Joseph R Scalea
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and
| | - Robert R Redfield
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and
| | - David P Foley
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI; and.,Veterans Administration Surgical Services, William S. Middleton Memorial Veterans Hospital, Madison, WI
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Optimization of Perioperative Conditions to Prevent Ischemic Cholangiopathy in Donation After Circulatory Death Donor Liver Transplantation. Transplantation 2016; 100:1699-704. [DOI: 10.1097/tp.0000000000001204] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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48
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Bruni A, Pepper AR, Gala-Lopez B, Pawlick R, Abualhassan N, Crapo JD, Piganelli JD, Shapiro AMJ. A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model. Islets 2016; 8:e1190058. [PMID: 27220256 PMCID: PMC4987021 DOI: 10.1080/19382014.2016.1190058] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Islet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin anti-inflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation. However, the administration of MnP (BMX-001) in a DCD islet isolation and transplantation model has yet to be established. In this study, murine donors were subjected to a 15-min warm ischemic (WI) period prior to isolation and culture with or without MnP. Subsequent to one-hour culture, islets were assessed for in vitro viability and in vivo function. A 15-minute WI period significantly reduced islet yield, regardless of MnP-treatment relative to yields from standard isolation. MnP-treated islets did not improve islet viability compared to DCD islets alone. MnP-treatment did significantly reduce the presence of extracellular reactive oxygen species (ROS) (p < 0 .05). Marginal, syngeneic islets (200 islets) transplanted under the renal capsule exhibited similar in vivo outcomes regardless of WI or MnP-treatment. DCD islet grafts harvested 7 d post-transplant exhibited sustained TNF-α and IL-10, while MnP-treated islet-bearing grafts demonstrated reduced IL-10 levels. Taken together, 15-minute WI in murine islet isolation significantly impairs islet yield. DCD islets do indeed demonstrate in vivo function, though MnP therapy was unable to improve viability and engraftment outcomes.
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Affiliation(s)
- Antonio Bruni
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Andrew R. Pepper
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
| | - Boris Gala-Lopez
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - Rena Pawlick
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
| | - Nasser Abualhassan
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
| | - James D. Crapo
- Department of Medicine, National Jewish Health, Denver, CO, USA, and BioMimetix JV, LLC, Englewood, CO, USA
| | - Jon D. Piganelli
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- BioMimetix JV, LLC, Englewood, CO, USA
| | - A. M. James Shapiro
- Clinical Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada
- Department of Surgery, University of Alberta, Edmonton, AB, Canada
- CONTACT A.M. James Shapiro, MD, PhD, Professor, Director of Clinical Islet and Living Donor Liver Transplant Programs, Canada Research Chair in Transplantation Surgery and Regenerative MedicineClinical Islet Transplant Program, University of Alberta, 2000 College Plaza, 8215-112th St, Edmonton T6G 2C8, Alberta, Canada
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49
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Nemes B, Gámán G, Polak WG, Gelley F, Hara T, Ono S, Baimakhanov Z, Piros L, Eguchi S. Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation. Expert Rev Gastroenterol Hepatol 2016; 10:841-59. [PMID: 26831547 DOI: 10.1586/17474124.2016.1149062] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.
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Affiliation(s)
- Balázs Nemes
- a Department of Organ Transplantation, Faculty of Medicine, Institute of Surgery , University of Debrecen , Debrecen , Hungary
| | - György Gámán
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Wojciech G Polak
- c Department of Surgery, Division of Hepatopancreatobiliary and Transplant Surgery, Erasmus MC , University Medical Center Rotterdam , Rotterdam , The Netherlands
| | - Fanni Gelley
- d Dept of Internal medicine and Gastroenterology , Polyclinic of Hospitallers Brothers of St. John of God , Budapest , Hungary
| | - Takanobu Hara
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Shinichiro Ono
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Zhassulan Baimakhanov
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
| | - Laszlo Piros
- b Clinic of Transplantation and Surgery , Semmelweis University , Budapest , Hungary
| | - Susumu Eguchi
- e Department of Surgery , Nagasaki University Graduate School of Biomedical Sciences , Nagasaki , Japan
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50
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Abdominal regional in-situ perfusion in donation after circulatory determination of death donors. Curr Opin Organ Transplant 2016; 21:322-8. [DOI: 10.1097/mot.0000000000000315] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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