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      Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

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          Abstract

          AIM

          To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use.

          METHODS

          The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.

          RESULTS

          DCD graft survival predictors were primary indication for transplant ( P = 0.066), retransplantation ( P = 0.176), MELD > 25 ( P = 0.05), cold ischemia > 10 h ( P = 0.292) and donor hepatectomy time > 60 min ( P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.

          CONCLUSION

          The DCD-RI score independently predicted graft loss ( P < 0.001) and the DCD-RI class predicted graft survival ( P < 0.001).

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          Most cited references33

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          Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.

          Kim M Olthoff, Laura Kulik, Benjamin Samstein … (2010)
          Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin >or=10mg/dL on day 7, international normalized ratio >or=1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk = 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk = 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function. (c) 2010 AASLD.
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            Survival outcomes following liver transplantation (SOFT) score: a novel method to predict patient survival following liver transplantation.

            A. Rana, M A Hardy, K. Halazun … (2008)
            It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21,673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30,321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.
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              Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long-term outcomes from a single center.

              David Foley, Luis Fernandez, Glen Leverson … (2011)
              This study evaluates the long-term outcomes, biliary complication rates, and risk factors for biliary complications after liver transplantation from "donation after cardiac death" (DCD) donors. Recent enthusiasm toward increased use of DCD donors' livers is mitigated by high biliary complication rates. Predictive risk factors for the development of biliary complications after DCD liver transplantation remain incompletely defined. We performed a retrospective review of 1157 "donation after brain death" (DBD) and 87 DCD liver transplants performed between January 1, 1993, and December 31, 2008. Patient and graft survivals and complication rates within the first year of transplantation were compared between DBD and DCD groups. Cox proportional hazards models were used to assess the influence of potential risk factors. Patient survival was significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 84%, 68%, 54%, and 54% vs DBD: 91%, 81%, 67%, and 58%; P < 0.01). Graft survival was also significantly lower in the DCD group compared with the DBD group at 1, 5, 10, and 15 years (DCD: 69%, 56%, 43%, 43% vs DBD: 86%, 76%, 60%, 51%; P < 0.001). Rates of overall biliary complications (OBC) (DCD: 47% vs DBD: 26%; P < 0.01) and ischemic cholangiopathy (IC) (DCD: 34% vs DBD: 1%; P < 0.01) were significantly higher in the DCD group. Donor age [hazard ratio (HR): 1.04; P < 0.01] and donor age greater than 40 years (HR: 3.13; P < 0.01) were significant risk factors for the development of OBC. Multivariate analysis revealed that cold ischemic time (CIT) greater than 8 hours (HR: 2.46; P = 0.05) and donor age greater than 40 years (HR: 2.90; P < 0.01) significantly increased the risk of IC. Long-term patient and graft survival after DCD liver transplantation remain significantly lower but acceptable when compared with DBD liver transplantations. Donor age and CIT greater than 8 hours are the strongest predictors for the development of IC. Careful selection of younger DCD donors and minimization of CIT may limit the incidence of severe biliary complications and improve the successful utilization of DCD donors' livers.
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                Author and article information

                Journal
                Journal ID (nlm-ta): World J Transplant
                Journal ID (publisher-id): WJT
                Title: World Journal of Transplantation
                Publisher: Baishideng Publishing Group Inc
                ISSN (Electronic): 2220-3230
                Publication date (Print): 24 June 2017
                Publication date (Electronic): 24 June 2017
                Volume: 7
                Issue: 3
                Pages: 203-212
                Affiliations
                Shirin Elizabeth Khorsandi, Emmanouil Giorgakis, Hector Vilca-Melendez, John O’Grady, Michael Heneghan, Varuna Aluvihare, Abid Suddle, Kosh Agarwal, Krishna Menon, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, Wayel Jassem, Nigel Heaton, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, United Kingdom
                Author notes

                Author contributions: Khorsandi SE designed and wrote study; Giorgakis E performed the analysis and was involved in writing the manuscript; Vilca-Melendez H, O’Grady J, Heneghan M, Aluvihare V, Suddle A, Agarwal K, Menon K, Prachalias A, Srinivasan P, Rela M and Jassem W were all involved in the editing and review of the manuscript; Heaton N provided guidance in the manuscript composition and gave final institutional approval.

                Correspondence to: Nigel Heaton, Professor, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, United Kingdom. nigel.heaton@ 123456nhs.net

                Telephone: +44-20-32994801 Fax: +44-20-32993575

                Article
                Other ID: jWJT.v7.i3.pg203
                DOI: 10.5500/wjt.v7.i3.203
                PMC ID: 5487310
                SO-VID: c8489f77-e4b8-40a8-a028-6cd960ea4f8b
                Copyright © ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
                License:

                Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                Date received : 18 November 2016
                Date revision received : 21 January 2017
                Date accepted : 12 March 2017
                Categories
                Subject: Retrospective Cohort Study

                Keywords: liver transplant,donor after cardiac death,pediatric,adult,survival
                Data availability:
                Keywords: liver transplant, donor after cardiac death, pediatric, adult, survival

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