Skip to main content
SpringerLink
Log in

Immune-Mediated Liver Disease in the Transplanted Liver

  • Chapter
  • First Online:
Liver Immunology

  • 639 Accesses

Abstract

Liver transplantation has evolved as the treatment of choice for many patients with end-stage liver disease. Currently, survival posttransplant is excellent, with 10-year survival exceeding 65%. Causes of graft failure include recurrent disease, in particular autoimmune disease, alcoholic liver disease, and NAFLD. Immune-mediated injury is also a cause for graft failure, but this cause has proved to be less common nowadays. With the actual range of potent immunosuppressive agents and a greater use of a tailored approach, rejection is seen less frequently. Rejection may take the form of T-cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and plasma cell-rich hepatitis. On the opposite end of the spectrum, operational tolerance develops in a small proportion of liver transplant recipients. Finally, as indicated earlier, some autoimmune diseases can recur in the allograft.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Noreen SM, et al. OPTN/SRTR 2017 annual data report: liver. Am J Transplant. 2019;19(Suppl 2):184–283. https://doi.org/10.1111/ajt.15276.

    Article  Google Scholar 

  2. Bittermann T, Hubbard RA, Lewis JD, Goldberg DS. The use of induction therapy in liver transplantation is highly variable and is associated with post-transplant outcomes. Am J Transplant. 2019;19(12):3319–27. https://doi.org/10.1111/ajt.15513.

    Article  Google Scholar 

  3. Shaked A, DesMarais MR, Kopetskie H, Feng S, Punch JD, Levitsky J, et al. Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. Am J Transplant. 2019;19:1397–409.

    Article  CAS  Google Scholar 

  4. Jadlowiec CC, Morgan PE, Nehra AK, Hathcock MA, Kremers WK, Heimbach JK, et al. Not all cellular rejections are the same: differences in early and late hepatic allograft rejection. Liver Transplant. 2019;25:425–35.

    Article  Google Scholar 

  5. McCormack L, Dutkowski P, El-Badry AM, Clavien PA. Liver transplantation using fatty livers: always feasible? J Hepatol. 2011;54(5):1055–62.

    Article  Google Scholar 

  6. Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury: present concepts. J Gastroenterol Hepatol. 2011;26(Suppl 1):173–9.

    Article  CAS  Google Scholar 

  7. Zhai Y, Busuttil RW, Kupiec-Weglinski JW. Liver ischemia and reperfusion injury: new insights into mechanisms of innate-adaptive immune-mediated tissue inflammation. Am J Transplant. 2011;11(8):1563–9.

    Article  CAS  Google Scholar 

  8. Abu-Amara M, Yang SY, Tapuria N, Fuller B, Davidson B, Seifalian A. Liver ischemia/reperfusion injury: processes in inflammatory networks—a review. Liver Transpl. 2010;16(9):1016–32.

    Article  Google Scholar 

  9. Dhillon N, Walsh L, Krüger B, Ward SC, Godbold JH, Radwan M, et al. A single nucleotide polymorphism of Toll-like receptor 4 identifies the risk of developing graft failure after liver transplantation. J Hepatol. 2010;53(1):67–72.

    Article  CAS  Google Scholar 

  10. Jaeschke H, Woolbright BL. Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplant Rev (Orlando). 2012;26(2):103–14.

    Article  Google Scholar 

  11. Klaassen CD, Reisman SA. Nrf2 the rescue: effects of the antioxidative/electrophilic response on the liver. Toxicol Appl Pharmacol. 2010;244(1):57–65.

    Article  CAS  Google Scholar 

  12. Jegatheeswaran S, Siriwardena AK. Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery. HPB (Oxford). 2011;13(2):71–8.

    Article  Google Scholar 

  13. Tsuchihashi S, Fondevila C, Kupiec-Weglinski JW. Heme oxygenase system in ischemia and reperfusion injury. Ann Transplant. 2004;9(1):84–7.

    CAS  Google Scholar 

  14. Jassem W, Fuggle SV, Cerundolo L, Heaton ND, Rela M. Ischemic preconditioning of cadaver donor livers protects allografts following transplantation. Transplantation. 2006;81(2):169–74.

    Article  Google Scholar 

  15. Dal Ponte C, Alchera E, Follenzi A, Imarisio C, Prat M, Albano E, et al. Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury. Liver Transpl. 2011;17(4):474–82.

    Article  Google Scholar 

  16. Li F, Atz ME, Reed EF. Human leukocyte antigen antibodies in chronic transplant vasculopathy-mechanisms and pathways. Curr Opin Immunol. 2009;21(5):557–62.

    Article  CAS  Google Scholar 

  17. Kim PT, Demetris AJ, O’Leary JG. Prevention and treatment of liver allograft antibody-mediated rejection and the role of the ‘two-hit hypothesis’. Curr Opin Organ Transplant. 2016;21:209–18.

    Article  CAS  Google Scholar 

  18. Lee M. Antibody-mediated rejection after liver transplant. Gastroenterol Clin N Am. 2017;46:297–309.

    Article  Google Scholar 

  19. Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant. 2008;13(4):438–44.

    Article  Google Scholar 

  20. Kroemer A, Edtinger K, Li XC. The innate natural killer cells in transplant rejection and tolerance induction. Curr Opin Organ Transplant. 2008;13(4):339–43.

    Article  Google Scholar 

  21. Klein I, Crispe IN. Complete differentiation of CD8+ T cells activated locally within the transplanted liver. J Exp Med. 2006;203(2):437–47.

    Article  Google Scholar 

  22. Kern M, Popov A, Kurts C, Schultze JL, Knolle PA. Taking off the brakes: T cell immunity in the liver. Trends Immunol. 2010;31(8):311–7.

    Article  CAS  Google Scholar 

  23. Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol. 2003;3(1):51–62.

    Article  CAS  Google Scholar 

  24. McDonald B, McAvoy EF, Lam F, Gill V, de la Motte C, Savani RC, et al. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med. 2008;205(4):915–27.

    Article  CAS  Google Scholar 

  25. Shetty S, Weston CJ, Oo YH, Westerlund N, Stamataki Z, Youster J, et al. Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J Immunol. 2011;186(7):4147–55.

    Article  CAS  Google Scholar 

  26. Lalor PF, Edwards S, McNab G, Salmi M, Jalkanen S, Adams DH. Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells. J Immunol. 2002;169(2):983–92.

    Article  CAS  Google Scholar 

  27. Goddard S, Williams A, Morland C, Qin S, Gladue R, Hubscher SG, et al. Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. Transplantation. 2001;72(12):1957–67.

    Article  CAS  Google Scholar 

  28. Demetris AJ, Bellamy C, Hübscher SG, O’Leary J, Randhawa PS, Feng S, et al. 2016 comprehensive update of the Banff working group on liver allograft pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016;16(10):2816–35.

    Article  CAS  Google Scholar 

  29. Montgomery RA, Loupy A, Segev DL. Antibody-mediated rejection: new approaches in prevention and management. Am J Transplant. 2018;18(Suppl 3):3–17.

    Article  CAS  Google Scholar 

  30. Hogen R, DiNorcia J, Dhanireddy K. Antibody-mediated rejection: what is the clinical relevance? Curr Opin Organ Transplant. 2017;22:97–104.

    Article  CAS  Google Scholar 

  31. Hübscher SG, Adams DH, Buckels JA, McMaster P, Neuberger J, Elias E. Massive haemorrhagic necrosis of the liver after liver transplantation. J Clin Pathol. 1989;42(4):360–70.

    Article  Google Scholar 

  32. Banff Working Group on Liver Allograft Pathology. Importance of liver biopsy findings in immunosuppression management: biopsy monitoring and working criteria for patients with operational tolerance. Liver Transpl. 2012;18:1154–70.

    Article  Google Scholar 

  33. Feng S, Bucuvalas JC, Demetris AJ, Burrell BE, Spain KM, Kanaparthi S, et al. Evidence of chronic allograft injury in liver biopsies from long-term pediatric recipients of liver transplants. Gastroenterology. 2018;155:1838–51.

    Article  Google Scholar 

  34. Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, et al. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J Transplant. 2013;13:2865–74.

    Article  CAS  Google Scholar 

  35. O’Grady JG, Hardy P, Burroughs AK, Elbourne D, UK and Ireland Liver Transplant Study Group. Randomized controlled trial of tacrolimus versus microemulsified cyclosporin (TMC) in liver transplantation: poststudy surveillance to 3 years. Am J Transplant. 2007;7(1):137–41.

    Article  CAS  Google Scholar 

  36. Defrancq C, De Wilde N, Raes A, Van Biervliet S, Vande Velde S, et al. Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: evolution, risk factors, and impact on patient outcomes. Pediatr Transplant. 2019 May;23(3):e13388. https://doi.org/10.1111/petr.13388.

    Article  CAS  Google Scholar 

  37. Warlé MC, Metselaar HJ, Hop WC, Tilanus HW. Cytokine gene polymorphisms and acute liver graft rejection: a meta-analysis. Liver Transpl. 2005;11(1):19–26.

    Article  Google Scholar 

  38. de Reuver P, Pravica V, Hop W, Boor P, Metselaar HJ, Hutchinson IV, et al. Recipient ctla-4 +49 G/G genotype is associated with reduced incidence of acute rejection after liver transplantation. Am J Transplant. 2003;3(12):1587–94.

    Article  Google Scholar 

  39. Fisher J, Zeitouni N, Fan W, Samie FH. Immune checkpoint inhibitor therapy in solid organ transplant recipients: a patient-centered systematic review. J Am Acad Dermatol. 2020;82(6):1490–500. https://doi.org/10.1016/j.jaad.2019.07.005.

    Article  CAS  Google Scholar 

  40. Clarkson MR, Sayegh MH. T-cell costimulatory pathways in allograft rejection and tolerance. Transplantation. 2005;80(5):555–63.

    Article  Google Scholar 

  41. Kitchens WH, Uehara S, Chase CM, Colvin RB, Russell PS, Madsen JC. The changing role of natural killer cells in solid organ rejection and tolerance. Transplantation. 2006;81(6):811–7.

    Article  Google Scholar 

  42. Hanvesakul R, Spencer N, Cook M, Gunson B, Hathaway M, Brown R, et al. Donor HLA-C genotype has a profound impact on the clinical outcome following liver transplantation. Am J Transplant. 2008;8(9):1931–41.

    Article  CAS  Google Scholar 

  43. Rodríguez-Perálvarez M, Germani G, Tsochatzis E, Rolando N, Luong TV, Dhillon AP, et al. Predicting severity and clinical course of acute rejection after liver transplantation using blood eosinophil count. Transpl Int. 2012;25(5):555–63.

    Article  CAS  Google Scholar 

  44. Krenzien F, Keshi E, Splith K, Griesel S, Kamali K, Sauer IM, et al. Diagnostic biomarkers to diagnose acute allograft rejection after liver transplantation: systematic review and meta-analysis of diagnostic accuracy studies. Front Immunol. 2019;10:758. https://doi.org/10.3389/fimmu.2019.00758. eCollection 2019.

    Article  CAS  Google Scholar 

  45. Bolognesi M, Sacerdoti D, Mescoli C, Nava V, Bombonato G, Merkel C, et al. Acute liver rejection: accuracy and predictive values of Doppler US measurements—initial experience. Radiology. 2005;235(2):651–8.

    Article  Google Scholar 

  46. Höroldt BS, Burattin M, Gunson BK, Bramhall SR, Nightingale P, Hübscher SG, Neuberger JM. Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation? Liver Transpl. 2006;12:1144–51.

    Article  Google Scholar 

  47. Hübscher SG. What is the long-term outcome of the liver allograft? J Hepatol. 2011;55(3):702–17.

    Article  Google Scholar 

  48. Shaked A, Ghobrial RM, Merion RM, Shearon TH, Emond JC, Fair JH, A2ALL Study Group, et al. Incidence and severity of acute cellular rejection in recipients undergoing adult living donor or deceased donor liver transplantation. Am J Transplant. 2009;9(2):301–8.

    Article  CAS  Google Scholar 

  49. Calne RY. WOFIE hypothesis: some thoughts on an approach toward allograft tolerance. Transplant Proc. 1996;28:1152.

    CAS  Google Scholar 

  50. Thurairajah PH, Carbone M, Bridgestock H, Thomas P, Hebbar S, Gunson BK, et al. Late acute liver allograft rejection; a study of its natural history and graft survival in the current era. Transplantation. 2013;95:955–9.

    Article  Google Scholar 

  51. Neil DA, Hübscher SG. Current views on rejection pathology in liver transplantation. Transpl Int. 2010;23(10):971–83.

    Article  Google Scholar 

  52. Demetris A, Adams D, Bellamy C, Blakolmer K, Clouston A, Dhillon AP, et al. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An international panel. Hepatology. 2000;31(3):792–9.

    Article  CAS  Google Scholar 

  53. Nishida S, Pinna A, Verzaro R, Levi D, Kato T, Khan F, et al. Sirolimus (rapamycin)-based rescue treatment following chronic rejection after liver transplantation. Transplant Proc. 2001;33(1–2):1495.

    Article  CAS  Google Scholar 

  54. Pfitzmann R, Klupp J, Langrehr JM, Uhl M, Neuhaus R, Settmacher U, et al. Mycophenolate mofetil for immunosuppression after liver transplantation: a follow-up study of 191 patients. Transplantation. 2003;76(1):130–6.

    Article  CAS  Google Scholar 

  55. Shaikh OS, Demetris AJ. Idiopathic posttransplantation hepatitis? Liver Transpl. 2007;13(7):943–6.

    Article  Google Scholar 

  56. Miyagawa-Hayashino A, Haga H, Egawa H, Hayashino Y, Uemoto S, Manabe T. Idiopathic post-transplantation hepatitis following living donor liver transplantation, and significance of autoantibody titre for outcome. Transpl Int. 2009;22(3):303–12.

    Article  CAS  Google Scholar 

  57. Pischke S, Suneetha P, Baechlein C, Barg-Hock H, Heim A, Kamar N, et al. Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transpl. 2009;16(1):74–82.

    Article  Google Scholar 

  58. Ankcorn MJ, Ijaz S, Poh J, Elsharkawy AM, Smit E, Cramb R, et al. Toward systematic screening for persistent hepatitis E virus infections in transplant patients. Transplantation. 2018;102:1139–47.

    Article  Google Scholar 

  59. Evans HM, Kelly DA, McKiernan PJ, Hubscher S. Progressive histological damage in liver allografts following pediatric liver transplantation. Hepatology. 2006;43(5):1109–17.

    Article  Google Scholar 

  60. Seyam M, Neuberger JM, Gunson BK, Hubscher SG. Cirrhosis after orthotopic liver transplantation in the absence of primary disease recurrence. Liver Transpl. 2007;13(7):966–74.

    Article  Google Scholar 

  61. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol. 2010;10(11):753–66.

    Article  CAS  Google Scholar 

  62. Adams DH, Sanchez-Fueyo A, Samuel D. From immunosuppression to tolerance. J Hepatol. 2015;62(1 Suppl):S170–85.

    Article  CAS  Google Scholar 

  63. Feng S. Spontaneous and induced tolerance for liver transplant recipients. Curr Opin Organ Transplant. 2016;21:53–8.

    Article  CAS  Google Scholar 

  64. Jukes JP, Jones ND. Immunology in the Clinic Review Series; focus on host responses: invariant natural killer T cell activation following transplantation. Clin Exp Immunol. 2012;167(1):32–9.

    Article  CAS  Google Scholar 

  65. Sánchez-Fueyo A. Hot-topic debate on tolerance: immunosuppression withdrawal. Liver Transpl. 2011;17(Suppl 3):S69–73.

    Article  Google Scholar 

  66. Calne R, Friend P, Moffatt S, Bradley A, Hale G, Firth J, et al. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet. 1998;351:1701–2.

    Article  CAS  Google Scholar 

  67. Londoño MC, Rimola A, O’Grady J, Sanchez-Fueyo A. Immunosuppression minimization vs. complete drug withdrawal in liver transplantation. J Hepatol. 2013;59(4):872–9. https://doi.org/10.1016/j.jhep.2013.04.003.

    Article  Google Scholar 

  68. Vionnet J, Sánchez-Fueyo A. Biomarkers of immune tolerance in liver transplantation. Hum Immunol. 2018;79:388–94.

    Article  CAS  Google Scholar 

  69. Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010;120(6):1836–47.

    Article  CAS  Google Scholar 

  70. Zhang XX, Bian RJ, Wang J, Zhang QY. Relationship between cytokine gene polymorphisms and acute rejection following liver transplantation. Genet Mol Res. 2016 Apr 26;15(2) https://doi.org/10.4238/gmr.15027599.

  71. Bohne F, Martinez-Llordella M, Lozano JJ, Miquel R, Benítez C, Londoño MC, et al. Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation. J Clin Invest. 2012;122(1):368–82.

    Article  CAS  Google Scholar 

  72. Zarkhin V, Talisetti A, Li L, Wozniak LJ, McDiarmid SV, Cox K, et al. Expression of soluble HLA-G identifies favorable outcomes in liver transplant recipients. Transplantation. 2010;90(9):1000–5.

    Article  CAS  Google Scholar 

  73. Farid WR, Pan Q, van der Meer AJ, Ramakrishnaiah V, de Jonge J, Kwekkeboom J, et al. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transpl. 2012;18(3):290–7.

    Article  Google Scholar 

  74. Marín LA, Moya-Quiles MR, Miras M, Minguela A, Bermejo J, Ramírez P, et al. Evolution of soluble forms of CD86, CD95 and CD95L molecules in liver transplant recipients. Transpl Immunol. 2012;26(2–3):94–100.

    Article  CAS  Google Scholar 

  75. Smets F, Dobbelaere D, McKiernan P, Dionisi-Vici C, Broué P, Jacquemin E, et al. Phase I/II trial of liver-derived mesenchymal stem cells in pediatric liver-based metabolic disorders: a prospective, open label, multicenter, partially randomized, safety study of one cycle of heterologous human adult liver-derived progenitor cells (HepaStem) in urea cycle disorders and Crigler-Najjar syndrome patients. Transplantation. 2019;103:1903–15.

    Article  Google Scholar 

  76. Soeder Y, Loss M, Johnson CL, Hutchinson JA, Haarer J, Ahrens N, et al. First-in-human case study: multipotent adult progenitor cells for immunomodulation after liver transplantation. Stem Cells Transl Med. 2015;4:899–904.

    Article  CAS  Google Scholar 

  77. Casiraghi F, Perico N, Remuzzi G. Mesenchymal stromal cells for tolerance induction in organ transplantation. Hum Immunol. 2018;79:304–13.

    Article  Google Scholar 

  78. Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology. 2016;64:632–43.

    Article  CAS  Google Scholar 

  79. Kashyap R, Safadjou S, Chen R, Mantry P, Sharma R, Patil V, et al. Living donor and deceased donor liver transplantation for autoimmune and cholestatic liver diseases—an analysis of the UNOS database. J Gastrointest Surg. 2010;14:1362–9.

    Article  Google Scholar 

  80. Carbone M, Bufton S, Monaco A, Griffiths L, Jones DE, Neuberger JM. The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study. J Hepatol. 2013;59:490–4.

    Article  Google Scholar 

  81. Pells G, Mells GF, Carbone M, Newton JL, Bathgate AJ, Burroughs AK, et al. The impact of liver transplantation on the phenotype of primary biliary cirrhosis patients in the UK-PBC cohort. J Hepatol. 2013;59:67–73.

    Article  Google Scholar 

  82. Yoshida EM, Singh RA, Vartanian RK, Owen DA, Erb SR, Scudamore CH. Late recurrent post-transplant primary biliary cirrhosis in British Columbia. Can J Gastroenterol. 1997;11:229–33.

    Article  CAS  Google Scholar 

  83. Hashimoto E, Shimada M, Noguchi S, Taniai M, Tokushige K, Hayashi N, et al. Disease recurrence after living liver transplantation for primary biliary cirrhosis: a clinical and histological follow-up study. Liver Transpl. 2001;7:588–95.

    Article  CAS  Google Scholar 

  84. Klein R, Huizenga JR, Gips CH, Berg PA. Antimitochondrial antibody profiles in patients with primary biliary cirrhosis before orthotopic liver transplantation and titres of antimitochondrial antibody-subtypes after transplantation. J Hepatol. 1994;20:181–9.

    Article  CAS  Google Scholar 

  85. Neuberger J, Gunson B, Hubscher S, Nightingale P. Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl. 2004;10:488–91.

    Article  Google Scholar 

  86. Mason AL. The evidence supports a viral aetiology for primary biliary cirrhosis. J Hepatol. 2011;54(6):1312–4.

    Article  Google Scholar 

  87. Manousou P, Arvaniti V, Tsochatzis E, Isgro G, Jones K, Shirling G, et al. Primary biliary cirrhosis after liver transplantation: influence of immunosuppression and human leukocyte antigen locus disparity. Liver Transpl. 2010;16(1):64–73.

    Article  Google Scholar 

  88. Morioka D, Egawa H, Kasahara M, Jo T, Sakamoto S, Ogura Y, et al. Impact of human leukocyte antigen mismatching on outcomes of living donor liver transplantation for primary biliary cirrhosis. Liver Transpl. 2007;13(1):80–90.

    Article  Google Scholar 

  89. Blan V, Ruppert K, Demetris AJ, Ledneva T, Duquesnoy RJ, Detre KM, et al. Long-term outcome of human leukocyte antigen mismatching in liver transplantation: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. Hepatology. 2008;48(3):878–88.

    Article  Google Scholar 

  90. Robertson H, Kirby JA, Yip WW, Jones DE, Burt AD. Biliary epithelial-mesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis. Hepatology. 2007;45(4):977–81.

    Article  CAS  Google Scholar 

  91. Chu AS, Diaz R, Hui JJ, Yanger K, Zong Y, Alpini G, et al. Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis. Hepatology. 2011;53(5):1685–95.

    Article  Google Scholar 

  92. Charatcharoenwitthaya P, Pimentel S, Talwalkar JA, Enders FT, Lindor KD, Krom RA, et al. Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl. 2007;13:1236–45.

    Article  Google Scholar 

  93. Jacob DA, Neumann UP, Bahra M, Klupp J, Puhl G, Neuhaus R, et al. Long-term follow-up after recurrence of primary biliary cirrhosis after liver transplantation in 100 patients. Clin Transpl. 2006;20:211–20.

    Article  Google Scholar 

  94. Rowe IA, Webb K, Gunson BK, Mehta N, Haque S, Neuberger J. The impact of disease recurrence on graft survival following liver transplantation: a single centre experience. Transpl Int. 2008;21(5):459–65.

    Article  Google Scholar 

  95. Tischendorf JJ, Hecker H, Krüger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007;102(1):107–14.

    Article  Google Scholar 

  96. Gautam M, Cheruvattath R, Balan V. Recurrence of autoimmune liver disease after liver transplantation: a systematic review. Liver Transpl. 2006;12:1813–24.

    Article  Google Scholar 

  97. Graziadei IW, Wiesner RH, Batts KP, Marotta PJ, La Russo NF, Porayko MK, et al. Recurrence of primary sclerosing cholangitis after liver transplantation. Hepatology. 1999;29:1050–6.

    Article  CAS  Google Scholar 

  98. Jeyarajah DR, Netto GJ, Lee SP, Testa G, Abbasoglu O, Husberg BS, et al. Recurrent primary sclerosing cholangitis after orthotopic liver transplantation: is chronic rejection part of the disease process? Transplantation. 1998;27:1300–6.

    Article  Google Scholar 

  99. Graziadei IW. Recurrence of primary sclerosing cholangitis after liver transplantation. Liver Transpl. 2002;8:575–81.

    Article  Google Scholar 

  100. Graziadei IW. Live donor liver transplantation for primary sclerosing cholangitis: is disease recurrence increased? Curr Opin Gastroenterol. 2011;27(3):301–5.

    Article  Google Scholar 

  101. Steenstraten IC, Sebib Korkmaz K, Trivedi PJ, Inderson A, van Hoek B, Rodriguez Girondo MDM, et al. Systematic review with meta-analysis: risk factors for recurrent primary sclerosing cholangitis after liver transplantation. Aliment Pharmacol Ther. 2019;49:636–43.

    Article  Google Scholar 

  102. Alabraba E, Nightingale P, Gunson B, Hubscher S, Olliff S, Mirza D, et al. A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts. Liver Transpl. 2009;15(3):330–40.

    Article  Google Scholar 

  103. Bajer L, Slavcev A, Macinga P, Sticova E, Brezina J, Roder M, et al. Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease. World J Gastroenterol. 2018;24:4939–49.

    Article  CAS  Google Scholar 

  104. Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol. 2006;6(3):244–51.

    Article  CAS  Google Scholar 

  105. Trivedi PJ, Adams DH. Mucosal immunity in liver autoimmunity: a comprehensive review. J Autoimmun. 2013;46:97–111.

    Article  CAS  Google Scholar 

  106. Campsen J, Zimmerman MA, Trotter JF, Wachs M, Bak T, Steinberg T, et al. Clinically recurrent primary sclerosing cholangitis following liver transplantation: a time course. Liver Transpl. 2008;14(2):181–5.

    Article  Google Scholar 

  107. Maheshwari A, Yoo HY, Thuluvath PJ. Long-term outcome of liver transplantation in patients with PSC: a comparative analysis with PBC. Am J Gastroenterol. 2004;99(3):538–42.

    Article  Google Scholar 

  108. Gelson W, Hoare M, Dawwas MF, Vowler S, Gibbs P, Alexander G. The pattern of late mortality in liver transplant recipients in the United Kingdom. Transplantation. 2011;91(11):1240–4.

    Article  Google Scholar 

  109. Tripathi D, Neuberger J. Autoimmune hepatitis and liver transplantation: indications, results, and management of recurrent disease. Semin Liver Dis. 2009;29(3):286–96.

    Article  Google Scholar 

  110. Stirnimann G, Ebadi M, Czaja AJ, Montano-Loza AJ. Recurrent and De novo autoimmune hepatitis. Liver Transpl. 2019;25:152–66.

    Article  Google Scholar 

  111. Ilyas JA, O’Mahony CA, Vierling JM. Liver transplantation in autoimmune liver diseases. Best Pract Res Clin Gastroenterol. 2011;25(6):765–82.

    Article  Google Scholar 

  112. Hubscher SG. Recurrent autoimmune hepatitis after liver transplantation: diagnostic criteria, risk factors, and outcome. Liver Transpl. 2001;7:285–91.

    Article  CAS  Google Scholar 

  113. Liberal R, Longhi MS, Mieli-Vergani G, Vergani D. Pathogenesis of autoimmune hepatitis. Best Pract Res Clin Gastroenterol. 2011;25(6):653–64.

    Article  CAS  Google Scholar 

  114. Ayata G, Gordon FD, Lewis WD, Pomfret E, Pomposelli JJ, Jenkins RL, et al. Liver transplantation for autoimmune hepatitis: a long-term pathologic study. Hepatology. 2000;32:185–92.

    Article  CAS  Google Scholar 

  115. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2010;34(1):7–14.

    Article  CAS  Google Scholar 

  116. Montano-Loza AJ, Vargas-Vorackova F, Ma M, Bain VG, Burak K, Kumar T, et al. Incidence and risk factors associated with de novo autoimmune hepatitis after liver transplantation. Liver Int. 2012;32:1426–33.

    Article  Google Scholar 

  117. Mieli-Vergani G, Vergani D. De novo autoimmune hepatitis after liver transplantation. J Hepatol. 2004;40:3–7.

    Article  Google Scholar 

  118. Fiel MI, Agarwal K, Stanca C, Elhaji N, Kontorinis N, Thung S, et al. Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with HCV. Liver Transpl. 2008;14:861–71.

    Article  Google Scholar 

  119. Khettry U, Huang WY, Simpson MA, Pomfret EA, Pomposelli JJ, Lewis WD, et al. Patterns of recurrent hepatitis C after liver transplantation in a recent cohort of patients. Hum Pathol. 2007;38:443–52.

    Article  Google Scholar 

  120. Beal EW, Black SM, Michaels A. Autoimmune hepatitis in the liver transplant graft. Clin Liver Dis. 2017;21:381–401.

    Article  Google Scholar 

  121. Kerkar N, Vergani D. De novo autoimmune hepatitis – is this different in adults compared to children? J Autoimmun. 2018;95:26–33.

    Article  Google Scholar 

  122. Ekong UD, McKiernan P, Martinez M, Lobritto S, Kelly D, Ng VL, et al. Long-term outcomes of de novo autoimmune hepatitis in pediatric liver transplant recipients. Pediatr Transplant. 2017;21(6):e12945. https://doi.org/10.1111/petr.12945.

    Article  CAS  Google Scholar 

  123. Venick RS, McDiarmid SV, Farmer DG, Gornbein J, Martin MG, Vargas JH, et al. Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis. Am J Transplant. 2007;7:955–63.

    Article  CAS  Google Scholar 

  124. Aguilera I, Sousa JM, Gavilán F, Bernardos A, Wichmann I, Nuñez-Roldán A. Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation. Liver Transpl. 2004;10(9):1166–72.

    Article  Google Scholar 

  125. Aguilera I, Aguado-Dominguez E, Sousa JM, Nuñez-Roldan A. Rethinking de novo immune hepatitis, an old concept for liver allograft rejection: relevance of glutathione S-transferase T1 mismatch. World J Gastroenterol. 2018;24:3239–324.

    Article  Google Scholar 

  126. Clemente MG, Antonucci R, Mandato C, Cicotto L, Meloni A, Gridelli B, et al. Autoantibodies against CYP-2C19: a novel serum marker in pediatric De novo autoimmune hepatitis? Biomed Res Int. 2017;2017:3563278. https://doi.org/10.1155/2017/3563278.

    Article  CAS  Google Scholar 

  127. Covini G, Bredi E, Badalamenti S, Roncalli M, Aghemo A, Colombo M. Autoimmune hepatitis during ledipasvir/sofosbuvir treatment of hepatitis C: a case report. Hepatol Commun. 2018;2:1179–18.

    Article  Google Scholar 

  128. Vukotic R, Vitale G, D’Errico-Grigioni A, Muratori L, Andreone P. De novo autoimmune hepatitis in liver transplant: state-of-the-art review. World J Gastroenterol. 2016;22:2906–14.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Liver Studies, MRC Centre for Transplantation, Department of Inflammation Biology, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Julien Vionnet

  2. Transplantation Centre, University Hospital of Lausanne, Lausanne, Switzerland

    Julien Vionnet

  3. Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland

    Julien Vionnet

  4. Medical Research Council (MRC) Centre for Transplantation, Institute of Liver Studies, King’s College London, London, UK

    Alberto Sanchez-Fueyo

  5. Liver Unit, University Hospital Birmingham NHS Trust, Birmingham, UK

    James Neuberger

Authors
  1. Julien Vionnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberto Sanchez-Fueyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Neuberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, The University of California School of Medicine, Davis, CA, USA

    M. Eric Gershwin

  2. Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA

    John M. Vierling

  3. Department of Medicine, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

    Atsushi Tanaka

  4. President, Hannover Medical School, Hannover, Germany

    Michael P. Manns

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vionnet, J., Sanchez-Fueyo, A., Neuberger, J. (2020). Immune-Mediated Liver Disease in the Transplanted Liver. In: Gershwin, M.E., M. Vierling, J., Tanaka, A., P. Manns, M. (eds) Liver Immunology . Springer, Cham. https://doi.org/10.1007/978-3-030-51709-0_36

Download citation

Publish with us

Policies and ethics

Search

Navigation