Cholestasis Post-Liver Transplantation

Chapter
Part of the Clinical Gastroenterology book series (CG)

Abstract

Cholestasis occurs frequently after liver transplantation and has a very broad differential diagnosis. Cholestasis can occur anytime throughout the post-transplant period and may be intrahepatic or extrahepatic in origin. This chapter reviews the common causes of cholestasis in the post-transplant setting.

Keywords

Cholesterol Hepatitis Ischemia Glutathione Corticosteroid 

References

  1. 1.
    Arain MA, Attam R, Freeman ML. Advances in endoscopic management of biliary tract complications after liver transplantation. Liver Transpl. 2013;19:482–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Am J Transplant. 2013;13:253–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Thethy S, Thomson BNJ, Pleass H, et al. Management of biliary tract complications after orthotopic liver transplantation. Clin Transplant. 2004;18(6):647–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Scatton O, Meunier B, Cherqui D, et al. Randomized trial of choledocho-choledochostomy with or without a T-tube in orthotopic liver transplantation. Ann Surg. 2001;233(3):432–7.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Zoepf T, Maldonado-Lopez EJ, Hilgard P, et al. Balloon dilatation vs balloon dilatation plus bile duct endoprostheses for treatment of anastomotic biliary strictures after liver transplantation. Liver Transpl. 2006;12(1):88–94.PubMedCrossRefGoogle Scholar
  6. 6.
    Guichelaar MM, Benson JT, Malinchoc M, et al. Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation. Am J Transplant. 2003;3(7):885–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Sanchez-Urdazpal L, Batts KP, Gores GJ, et al. Increased bile duct complications in liver transplantation across the ABO barrier. Ann Surg. 1993;218(2):152–8.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Muiesan P, Girlanda R, Jassem W, Melendez HV, O’Grady J, Bowles M, Rela M, Heaton N. Single-center experience with liver transplantation from controlled non-heartbeating donors. Ann Surg. 2005;242(5):732–8.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Nguyen JH, Bonatti H, Dickson RC, Hewitt WR, Grewall HP, Willingham DL, Harnois DM, Schmitt TM, Machicao VI, Ghabril MS, Keaveny AP, Aranda-Michel J, Satyanarayana R, Rosser BG, Hinder RA, Steers JL, Hughes CB. Long-term outcomes of donation after cardiac death liver allografts from a single center. Clin Transplant. 2009;23:168–73.PubMedCrossRefGoogle Scholar
  10. 10.
    DeOliveira ML, Jassem W, Valente R, Khorsandi SE, Santori G, Prachalias A, Sirinivasan P, Rela M, Heaton N. Biliary complications after liver transplantation using grafts from donors after cardiac death: Results from a matched control study in a single large volume center. Ann Surg. 2011;254(5):716–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Foley DP, Fernandez LA, Leverson G, Anderson M, Mezrich J, Sollinger HW, D’Alessandro A. 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(4):817–25.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Van der Hilst CS, Ijtsma AJC, Bottema JT, van Hoek B, Dubbeld J, Metelaar HJ, Kazemier G, van den Berg AP, Porte RJ, Slooff MJH. The price of donation after cardiac death in liver transplantation: a prospective cost-effectiveness study. Transpl Int 2013.Google Scholar
  13. 13.
    Taner CB, Bulatao LG, Willingham DL, Perry DK, Siblesky L, Pungapong S, Aranda-Michel J, Keaveny AP, Kramer DJ, Nguyen JH. Events in procurement as risk factors to ischemic cholangiopathy in liver transplantation using donation after cardiac death donors. Liver Transpl. 2012;18:101–12.Google Scholar
  14. 14.
    Abt P, Crawford M, Desai N, et al. Liver transplantation from controlled non-heart-beating donors: an increased incidence of biliary complications. Transplantation. 2003;75(10):1659–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Taner CB, Bulatao IG, Perry DK, Sibulesky L, Willingham DL, Kramer DJ, Nguyen JH. Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors. Transplant Int. 2012;25:838–46.CrossRefGoogle Scholar
  16. 16.
    Cadranel JF, Erlinger S, Desruenne M, et al. Chronic administration of cyclosporine A induces a decrease in hepatitis excretory function in man. Dig Dis Sci. 1992;37(10):1473–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Buquets J, Figueras J, Serrano T, et al. Post reperfusion biopsies are useful in predicting complications after liver transplantation. Liver Transpl. 2001;7(5):432–5.CrossRefGoogle Scholar
  18. 18.
    Lee YM, Obrien CB, Yamashiki N, et al. Preservation injury patterns in liver transplantation associated with poor prognosis. Transplant Proc. 2003;35:2964–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Cutrin JC, Cantino D, Biasi F, et al. Reperfusion damage to the bile canaliculi in transplanted human liver. Hepatology. 1996;24(5):1053–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Kukan M, Haddad PS. Role of hepatocytes and bile duct cells in preservation-reperfusion injury of liver grafts. Liver Transpl. 2001;7(5):381–400.PubMedCrossRefGoogle Scholar
  21. 21.
    Nakanuma Y, Sasaki M. Expression of blood group-related antigens in the intrahepatic biliary tree and hepatocytes in normal livers and various hepatobiliary diseases. Hepatology. 1989;10(2):174–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant. 2005;5(11):2605–10.PubMedCrossRefGoogle Scholar
  23. 23.
    Deltenre P, Valla DC. Ischemic cholangiopathy. J Hepatol. 2006;44:806–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Jain A, Costa G, Marsh W, et al. Thrombotic and nonthrombotic hepatic artery complications in adults and children following primary liver transplantation with long-term follow-up in 1000 consecutive patients. Transpl Int. 2006;19(1):27–37.PubMedCrossRefGoogle Scholar
  25. 25.
    Silva MA, Jambulingam PS, Gunson BK, et al. Hepatic artery thrombosis following orthotopic liver transplantation: a 10-year experience from a single Centre in the United Kingdom. Liver Transpl. 2006;12(1):146–51.PubMedCrossRefGoogle Scholar
  26. 26.
    Pastacaldi S, Teixeira R, Montalto P, Rolles K, Burroughs AK. Hepatic artery thrombosis after orthotopic liver transplantation: a review of nonsurgical causes. Liver Transpl. 2001;7:75–81.PubMedCrossRefGoogle Scholar
  27. 27.
    Levy GA, Marsden PA. Cigarette smoking—association with hepatic artry thrombosis. Liver Transpl. 2002;8(7):588–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Pinna AD, Smith CV, Furukawa H, Starzl TE, Fung JJ. Urgent revascularization of liver allografts after early hepatic artery thrombosis. Transplantation. 1996;62:1584–7.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kusne S, Blair JE. Viral and fungal infections after liver transplantation—part II. Liver Transpl. 2006;12(1):2–11.PubMedCrossRefGoogle Scholar
  30. 30.
    Trauner M, Fickert P, Stauber RE. Inflammation-induced cholestasis. J Gastroenterol Hepatol. 1999;14(10):946–59.PubMedCrossRefGoogle Scholar
  31. 31.
    Lefkowich JH. Bile ductular cholestasis: an ominous histopathologic sign related to sepsis and “cholangitis lenta”. Hum Pathol. 1982;13(1):19–24.CrossRefGoogle Scholar
  32. 32.
    Paya CV, Hermans PE, Wiesner RH, et al. Cytomegalovirus hepatitis in liver transplantation: prospective analysis of 93 consecutive orthotopic liver transplantations. J Infect Dis. 1989;160(5):752–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Martelius T, Krogerus L, Hockerstedt K, Bruggeman C, Lautenschlager I. Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts. Hepatology. 1998;27(4):996–1002.PubMedCrossRefGoogle Scholar
  34. 34.
    Evans PC, Coleman N, Wreghitt TG, Wright DG, Alexander GJ. Cytomegalovirus infection of bile duct epithelial cells, hepatic artery and portal venous endothelium in relation to chronic refection of liver grafts. J Hepatol. 1999;31(5):913–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Lautenschlager I, Hockerstedt K, Taskinen E. Histologic findings associated with CMV infection in liver transplantation. Transplant Proc. 2003;35(2):819.PubMedCrossRefGoogle Scholar
  36. 36.
    Lautenschlager I, Lappalainen M, Linnavuori K, Suni J, Hockerstedt K. CMV infection is usually associated with concurrent HHV-6 and HHV-7 antigenemia in liver transplant patients. J Clin Virol. 2002;25 Suppl 2:S57–61.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan FK, Shaffer EA. Cholestatic effects of cyclosporine in the rat. Transplantation. 1997;63(11):1574–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Deters M, Klabunde T, Kirchner G, Resch K, Kaever V. Sirolimus/cyclosporine/tacrolimus interactions on bile flow and biliary excretion of immunosuppressants in a subchronic bile fistula rat model. Br J Pharmacol. 2002;136(4):604–12.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Sanchez-Campos S, Lopez-Acebo R, Gonzalez P, et al. Cholestasis and alteration of glutathione metabolism induced by tacrolimus (FK506) in the rat. Transplantation. 1998;66(1):84–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Deters M, Kirchner G, Koal T, Rech K, Kaever V. Everolimus/cyclosporine interactions on bile flow and biliary excretion of bile salts and cholesterol in rats. Dig Dis Sci. 2004;49(1):30–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Romagnuolo J, Sadowski DC, Lalor E, Jewell L, Thomson AB. Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. Can J Gastroenterol. 1998;12(7):479–83.PubMedGoogle Scholar
  42. 42.
    Vierling JM, Fennell Jr RH. Histopathology of early and late human hepatic allograft rejection: evidence of progressive destruction of interlobular bile ducts. Hepatology. 1985;5(6):1076–82.PubMedCrossRefGoogle Scholar
  43. 43.
    Nawaz S, Fennell RH. Apoptosis of bile duct epithelial cells in hepatic allograft rejection. Histopathology. 1994;25(2):137–42.PubMedCrossRefGoogle Scholar
  44. 44.
    Savier E, Lemasters JJ, Thurman RG. Kupffer cells participate in rejection following liver transplantation in the rat. Transpl Int. 1994;7 Suppl 1:S183–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Neuberger J. Incidence, timing, and risk factors for acute and chronic rejection. Liver Transpl Surg. 1999;5(4 Suppl 1):S30–6.PubMedGoogle Scholar
  46. 46.
    Batts KP. Acute and chronic hepatic allograft rejection; pathology and classification. Liver Transpl Surg. 1999;5(4 Suppl 1):S21–9.PubMedGoogle Scholar
  47. 47.
    Demetris AJ, Murase N, Ye Q, et al. Analysis of chronic rejection and obliterative arteriopathy. Possible contributions of donor antigen-presenting cells and lymphatic disruption. Am J Pathol. 1997;150(2):563–78.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Neuberger J. Recurrent primary biliary cirrhosis. Liver Transpl. 2003;9(6):539–46.PubMedCrossRefGoogle Scholar
  49. 49.
    Sylvestre PB, Batts KP, Burgart LJ, Poterucha JJ, Wiesner RH. Recurrence of primary biliary cirrhosis after liver transplantation: histologic estimate of incidence and natural history. Liver Transpl. 2003;9(10):1086–93.PubMedCrossRefGoogle Scholar
  50. 50.
    Jacob DA, Neumann UP, Bahra M, Langrehr JM, Nauhaus P. Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival. Transplant Proc. 2005;37(4):1691–2.PubMedCrossRefGoogle Scholar
  51. 51.
    Fosby B, Karlsen TH, Melum E. Recurrence and rejection in liver transplantation for primary sclerosing cholangitis. World J Gastroenterol. 2012;18(1):1–15.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Goss JA, Shackleton CR, Farmer DG, et al. Orthotopic liver transplantation for primary biliary sclerosing cholangitis. A 12-year single center experience. Ann Surg. 1997;225(5):472–81.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Brandsaeter B, Schrumpf E, Bentdal O, et al. Recurrent primary sclerosing cholangitis after liver transplantation: a magnetic resonance cholangiography study with analysis of predictive factors. Liver Transpl. 2005;11(11):1361–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Kugelmas M, Spiegelman P, Osgood MJ. Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2003;9(7): 727–32.PubMedCrossRefGoogle Scholar
  55. 55.
    Alabraba E, Nightingale P, Gunson B, Hubscher S, Olliff S, Mirza D, Neuberger J. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl. 2009;15:330–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Taga SA, Washington MK, Terrault N, et al. Cholestatic hepatitis C in liver allografts. Liver Transpl Surg. 1998;4(4):304–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Antonini TM, Sebagh M, Roque-Alfonso AM, Sobesky R, Coilly A, Vaghefi P, Adam R, Vittecoq D, Castaing D, Samuel D, Duclos-Vallee JC. Fibrosing Cholestatic hepatitis in HIV/HCV co-infected transplant patients—usefulness of early markers after liver transplantation. Am J Transplant. 2011;11:1686–95.PubMedCrossRefGoogle Scholar
  58. 58.
    Colter SJ, Taylor SL, Gretch DR, et al. Hyperbilirubinemia and cholestatic liver injury in hepatitis C-infected liver transplant recipients. Am J Gastroenterol. 2000;95(3):753–9.CrossRefGoogle Scholar
  59. 59.
    Coilly A, Roche B, Dumortier J, Leroy V, Botta-Fridlund D, Radenne S, Pageaux GP, Si-Ahmed SN, Guillaud O, Antonini TM, Haim-Boukobza S, Roque-Afonso AM, Samuel D, Duclos-Vallee JC. Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation, a multicenter experience. J Hepatol. 2013;60:78–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of TransplantMayo ClinicJacksonvilleUSA
  2. 2.Gastroenterology and HepatologyMayo ClinicRochesterUSA

Personalised recommendations