Predictors of Biliary Strictures After Liver Transplantation Among Recipients of DCD (Donation After Cardiac Death) Grafts

  • Divyanshoo R. KohliEmail author
  • M. Edwyn Harrison
  • Abimbola O. Adike
  • Bara El Kurdi
  • Norio Fukami
  • Douglas O. Faigel
  • Rahul Pannala
  • Adyr A. Moss
  • Bashar A. Aqel
Original Article



Biliary strictures are a common complication among donation after cardiac death (DCD) liver transplantation (LT) recipients and may require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. We evaluated the risk factors associated with development of biliary strictures in DCD LT recipients.


DCD LT recipients who underwent transplantation from 2012 to 2017 were divided into 2 groups: (a) those with anastomotic or non-anastomotic biliary strictures who required ERCP (“stricture group”) and (b) those who did not require ERCP or had cholangiograms without evidence of biliary strictures (“non-stricture group”). Clinical data, cholangiograms and laboratory values at day 0 and day 7 after LT were compared between the two groups.


Forty-nine of the 100 DCD LT recipients underwent ERCP. Thirty-four of these 49 LT recipients had evidence of anastomotic or non-anastomotic biliary strictures (stricture group), while the remaining 66 LT recipients comprised the non-stricture group. Donor age was significantly higher in stricture group compared to non-stricture group (49.2 ± 1.8 vs 42.8 ± 1.57 years, respectively; p = 0.01). The stricture group had a significantly higher total bilirubin at day 0 (3.5 ± 0.37 vs 2.6 ± 0.21 mg/dL; p = 0.02) and INR at day 7 (1.24 ± 0.06 vs 1.13 ± 0.01; p = 0.048) compared to the non-stricture group. Multi-variate analysis demonstrated significant association between biliary strictures and total bilirubin at day 0 of LT and age of donor.


Biliary strictures occur frequently in DCD LT recipients and may be associated with older age of donor. Hyperbilirubinemia immediately after transplant and higher INR in the first 7 days after transplant may predict subsequent development of biliary strictures.


Biliary strictures Donation after cardiac death Liver transplant 



Endoscopic retrograde cholangiopancreatography


Liver transplant


Donation after cardiac death


Donation after brain death


Author’s contribution

Dr. Kohli collected and analyzed the data, reviewed literature and wrote the initial draft; Drs. Harrison, Fukami, Faigel and Pannala performed ERCP procedures and edited the manuscript; Dr. Moss edited the manuscript and provided critical inputs, Drs. Adike and El Kurdi collected data, Dr. Aqel analyzed the data, revised the manuscript and served as principal investigator for the study.

Compliance with ethical standards

Conflict of interest

None of the authors have any conflict of interest to report.


  1. 1.
    Croome KP, Mathur AK, Lee DD, et al. Outcomes of donation after cardiac death liver grafts from donors ≥ 50 years of age: a multi-center analysis. Transplantation. 2018;102:1108–1114.CrossRefGoogle Scholar
  2. 2.
    O’Neill S, Roebuck A, Khoo E, Wigmore SJ, Harrison EM. A meta-analysis and meta-regression of outcomes including biliary complications in donation after cardiac death liver transplantation. Transpl Int. 2014;27:1159–1174.CrossRefGoogle Scholar
  3. 3.
    Kalisvaart M, de Haan JE, Polak WG, et al. Comparison of postoperative outcomes between donation after circulatory death and donation after brain death liver transplantation using the comprehensive complication index. Ann Surg. 2017;266:772–778.CrossRefGoogle Scholar
  4. 4.
    Kohli DR, Vachhani R, Shah TU, BouHaidar DS, Siddiqui MS. Diagnostic accuracy of laboratory tests and diagnostic imaging in detecting biliary strictures after liver transplantation. Dig Dis Sci. 2017;62:1327–1333. Scholar
  5. 5.
    Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Biliary complications after liver transplantation: old problems and new challenges. Am J Transpl. 2013;13:253–265.CrossRefGoogle Scholar
  6. 6.
    Kohli DR, Shah TU, BouHaidar DS, Vachhani R, Siddiqui MS. Significant infections in liver transplant recipients undergoing endoscopic retrograde cholangiography are few and unaffected by prophylactic antibiotics. Dig Liver Dis. 2018;50:1220–1224.CrossRefGoogle Scholar
  7. 7.
    ASGE Standards of Practice Committee, Chandrasekhara V, Khashab MA, et al. Adverse events associated with ERCP. Gastrointest Endosc. 2017;85:32–47.CrossRefGoogle Scholar
  8. 8.
    Tabibian JH, Girotra M, Yeh H-C, et al. Risk factors for early repeat ERCP in liver transplantation patients with anastomotic biliary stricture. Ann Hepatol. 2015;14:340–347.CrossRefGoogle Scholar
  9. 9.
    Foley DP, Fernandez LA, Leverson G, et al. Biliary complications after liver transplantation from donation after cardiac death donors: an analysis of risk factors and long term outcomes from a single center. Ann Surg. 2011;253:817–825.CrossRefGoogle Scholar
  10. 10.
    Villa NA, Harrison ME. Management of biliary strictures after liver transplantation. Gastroenterol Hepatol. 2015;11:316–328.Google Scholar
  11. 11.
    Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010;16:943–949.CrossRefGoogle Scholar
  12. 12.
    Saidi RF. Utilization of expanded criteria donors in liver transplantation. Int J Organ Transpl Med. 2013;4:46–59.Google Scholar
  13. 13.
    Bhati C, Idowu MO, Sanyal AJ, et al. Long-term outcomes in patients undergoing liver transplantation for nonalcoholic steatohepatitis-related cirrhosis. Transplantation. 2017;101:1867–1874.CrossRefGoogle Scholar
  14. 14.
    Mateo R, Cho Y, Singh G, et al. Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data. Am J Transpl. 2006;6:791–796.CrossRefGoogle Scholar
  15. 15.
  16. 16.
    Ortega-Deballon I, Hornby L, Shemie SD. Protocols for uncontrolled donation after circulatory death: a systematic review of international guidelines, practices and transplant outcomes. Crit Care. 2015;19:268–282.CrossRefGoogle Scholar
  17. 17.
    Taner CB, Bulatao IG, Willingham DL, et al. Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors. Liver Transpl. 2012;18:100–111.CrossRefGoogle Scholar
  18. 18.
    Orman ES, Barritt AS, Wheeler SB, Hayashi PH. Declining liver utilization for transplant in the United States and the impact of donation after cardiac death. Liver Transpl. 2013;19:59–68.CrossRefGoogle Scholar
  19. 19.
    Wells M, Croome KM, Janik T, Hernandez-Alejandro RM, Chandok NM. Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: a systematic review and meta-analysis. Can J Gastroenterol Hepatol. 2014;28:103–108.CrossRefGoogle Scholar
  20. 20.
    Croome KP, Lee DD, Perry DK, et al. 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.CrossRefGoogle Scholar
  21. 21.
    den Dulk AC, Sebib Korkmaz K, de Rooij B-JF, et al. High peak alanine aminotransferase determines extra risk for nonanastomotic biliary strictures after liver transplantation with donation after circulatory death. Transpl Int. 2015;28:492–501.CrossRefGoogle Scholar
  22. 22.
    Mocchegiani F, Vincenzi P, Lanari J, et al. Immunological risk factors in biliary strictures after liver transplantation. Ann Transpl. 2015;20:218–224.CrossRefGoogle Scholar
  23. 23.
    Forrest EA, Reiling J, Lipka G, Fawcett J. Risk factors and clinical indicators for the development of biliary strictures post liver transplant: significance of bilirubin. World J Transpl. 2017;7:349–358.CrossRefGoogle Scholar
  24. 24.
    Sachdev A, Kashyap JR, D’Cruz S, Kohli DR, Singh R, Singh K. Safety and efficacy of therapeutic endoscopic interventions in the management of biliary leak. Indian J Gastroenterol. 2012;31:253–257.CrossRefGoogle Scholar
  25. 25.
    Adike A, Buras M, Kurdi BE, Reddy KS, Moss AA, Aqel B. Outcomes of liver transplantation using organ donation after cardiac death (DCD) versus organ donation after brain death (DBD): a single center experience. Gastroenterology. 2017;152:S1121–S1122.CrossRefGoogle Scholar
  26. 26.
    Vries D, Boudewijn A, Koornstra JJ, Foe LT, Porte RJ, et al. Impact of non-anastomotic biliary strictures after liver transplantation on healthcare consumption, use of ionizing radiation and infectious events. Clin Transpl. 2016;30:81–89.CrossRefGoogle Scholar
  27. 27.
    Verdonk RC, Buis CI, van der Jagt EJ, et al. Nonanastomotic biliary strictures after liver transplantation, part 2: management, outcome, and risk factors for disease progression. Liver Transpl. 2007;13:725–732.CrossRefGoogle Scholar
  28. 28.
    Chan EY, Olson LC, Kisthard JA, et al. Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors. Liver Transpl. 2008;14:604–610.CrossRefGoogle Scholar
  29. 29.
    Axelrod DA, Lentine KL, Xiao H, et al. National assessment of early biliary complications following liver transplantation: incidence and outcomes. Liver Transpl. 2014;20:446–456.CrossRefGoogle Scholar
  30. 30.
    Buxbaum JL, Biggins SW, Bagatelos KC, Ostroff JW. Predictors of endoscopic treatment outcomes in the management of biliary problems after liver transplantation at a high-volume academic center. Gastrointest Endosc. 2011;73:37–44.CrossRefGoogle Scholar
  31. 31.
    Pasha SF, Harrison ME, Das A, et al. Endoscopic treatment of anastomotic biliary strictures after deceased donor liver transplantation: outcomes after maximal stent therapy. Gastrointest Endosc. 2007;66:44–51.CrossRefGoogle Scholar
  32. 32.
    Verdonk RC, Buis CI, Porte RJ, et al. Anastomotic biliary strictures after liver transplantation: Causes and consequences. Liver Transpl. 2006;12:726–735.CrossRefGoogle Scholar
  33. 33.
    Aparício DPDS, Otoch JP, Montero EFDS, Khan MA, Artifon ELDA. Endoscopic approach for management of biliary strictures in liver transplant recipients: a systematic review and meta-analysis. United Eur Gastroenterol J. 2017;5:827–845.CrossRefGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  • Divyanshoo R. Kohli
    • 1
    • 2
    Email author
  • M. Edwyn Harrison
    • 1
  • Abimbola O. Adike
    • 1
  • Bara El Kurdi
    • 1
  • Norio Fukami
    • 1
  • Douglas O. Faigel
    • 1
  • Rahul Pannala
    • 1
  • Adyr A. Moss
    • 3
  • Bashar A. Aqel
    • 1
  1. 1.Division of Gastroenterology and HepatologyMayo ClinicPhoenixUSA
  2. 2.Division of Gastroenterology and HepatologyKansas City VA Medical CenterKansas CityUSA
  3. 3.Department of SurgeryMayo ClinicPhoenixUSA

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