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Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel Disease

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Abstract

Nearly one-third of patients with inflammatory bowel disease (IBD) have abnormal liver tests, which can be indicative of underlying hepatic disease. Primary sclerosing cholangitis has a clear association with ulcerative colitis, but other autoimmune disorders such as autoimmune hepatitis (AIH) have also been associated with IBD. AIH may also occur in the setting of an overlap syndrome or in the setting of medications, particularly tumor necrosis factor alpha inhibitors. Importantly, some studies have shown that IBD patients with AIH fail treatment more frequently than IBD patients without AIH. This review will focus on the clinical characteristics, diagnosis, and management of autoimmune hepatitis in inflammatory bowel disease patients.

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References

  1. Rojas-Feria M, Castro M, Suárez E, Ampuero J, Romero-Gómez M. Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver. World J Gastroenterol. 2013;19:7327–7340.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16:1598–1619.

    Article  PubMed  Google Scholar 

  3. Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol. 2008;14:331–337.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Perdigoto R, Carpenter HA, Czaja AJ. Frequency and significance of chronic ulcerative colitis in severe corticosteroid-treated autoimmune hepatitis. J Hepatol. 1992;14:325–331.

    Article  CAS  PubMed  Google Scholar 

  5. Bailey J, Sreepati G, Love J, et al. Autoimmune hepatitis with inflammatory bowel disease is distinct and may be more refractory to traditional treatment. Am J Gastroenterol. 2014;109:S149.

    Google Scholar 

  6. Trivedi PJ, Chapman RW. PSC, AIH and overlap syndrome in inflammatory bowel disease. Clin Res Hepatol Gastroenterol. 2012;36:420–436.

    Article  CAS  PubMed  Google Scholar 

  7. Knight C, Murray KF. Hepatobiliary associations with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2009;3:681–691.

    Article  PubMed  Google Scholar 

  8. Liberal R, Grant CR, Longhi MS, Mieli-Vergani G, Vergani D. Diagnostic criteria of autoimmune hepatitis. Autoimmun Rev. 2014;13:435–440.

    Article  CAS  PubMed  Google Scholar 

  9. Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48:169–176.

    Article  PubMed  Google Scholar 

  10. Ordonez F, Lacaille F, Canioni D, et al. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis. 2012;18:1809–1817.

    Article  PubMed  Google Scholar 

  11. Chassaing B, Etienne-Mesmin L, Gewirtz AT. Microbiota-liver axis in hepatic disease. Hepatology. 2014;59:328–339.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Trivedi PP, Jena GB. Ulcerative colitis-induced hepatic damage in mice: studies on inflammation, fibrosis, oxidative DNA damage and GST-P expression. Chem Biol Interact. 2013;201:19–30.

    Article  CAS  PubMed  Google Scholar 

  13. Celaj S, Gleeson MW, Deng J, et al. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury. Lab Invest. 2014;94:938–949.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Czaja AJ. Diagnosis and management of the overlap syndromes of autoimmune hepatitis. Can J Gastroenterol. 2013;27:417–423.

    PubMed Central  PubMed  Google Scholar 

  15. Boberg KM, Chapman RW, Hirschfield GM, et al. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol. 2011;54:374–385.

    Article  PubMed  Google Scholar 

  16. Rojas CP, Bodicharla R, Campuzano-Zuluaga G, Hernandez L, Rodriguez MM. Autoimmune hepatitis and primary sclerosing cholangitis in children and adolescents. Fetal Pediatr Pathol. 2014;33:202–209.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Deneau M, Jensen MK, Holmen J, Williams MS, Book LS, Guthery SL. Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history. Hepatology. 2013;58:1392–1400.

    Article  PubMed  Google Scholar 

  18. Czaja AJ. The overlap syndromes of autoimmune hepatitis. Dig Dis Sci. 2013;58:326–343.

    CAS  PubMed  Google Scholar 

  19. Malik TA, Gutierrez AM, McGuire B, Zarzour JG, Mukhtar F, Bloomer J. Autoimmune hepatitis-primary sclerosing cholangitis overlap syndrome complicated by Crohn’s disease. Digestion. 2010;82:24–26.

    Article  PubMed  Google Scholar 

  20. Durazzo M, Premoli A, Paschetta E, Belci P, Spandre M, Bo S. Overlap syndromes of autoimmune hepatitis: an open question. Dig Dis Sci. 2013;58:344–348.

    Article  CAS  PubMed  Google Scholar 

  21. Floreani A, Rizzotto ER, Ferrara F, et al. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol. 2005;100:1516–1522.

    Article  PubMed  Google Scholar 

  22. Rabinovitz M, Demetris AJ, Bou-Abboud CF, Van Thiel DH. Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. Dig Dis Sci. 1992;37:1606–1611.

    Article  CAS  PubMed  Google Scholar 

  23. Lawrence SP, Sherman KE, Lawson JM, Goodman ZD. A 39 year old man with chronic hepatitis. Semin Liver Dis. 1994;14:97–105.

    Article  CAS  PubMed  Google Scholar 

  24. Wurbs D, Klein R, Terracciano LM, Berg PA, Bianchi L. A 28-year-old woman with a combined hepatitic/cholestatic syndrome. Hepatology. 1995;22:1598–1605.

    Article  CAS  PubMed  Google Scholar 

  25. Boberg KM, Fausa O, Haaland T, et al. Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology. 1996;23:1369–1376.

    Article  CAS  PubMed  Google Scholar 

  26. Protzer U, Dienes HP, Bianchi L, et al. Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis. Liver. 1996;16:274–282.

    Article  CAS  PubMed  Google Scholar 

  27. Luketic VA, Gomez DA, Sanyal AJ, Shiffman ML. An atypical presentation for primary sclerosing cholangitis. Dig Dis Sci. 1997;42:2009–2016.

    Article  CAS  PubMed  Google Scholar 

  28. McNair AN, Moloney M, Portmann BC, Williams R, McFarlane IG. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol. 1998;93:777–784.

    Article  CAS  PubMed  Google Scholar 

  29. Abdo AA, Bain VG, Kichian K, Lee SS. Evolution of autoimmune hepatitis to primary sclerosing cholangitis: a sequential syndrome. Hepatology. 2002;36:1393–1399.

    Article  PubMed  Google Scholar 

  30. Van Buuren HR, van Hoogstraten HJE, Terkivatan T, Schalm SW, Vleggaar FP. High prevalence of autoimmune hepatitis among patients with primary sclerosing cholangitis. J Hepatol.. 2000;33:543–548.

    Article  PubMed  Google Scholar 

  31. Hatzis GS, Vassiliou VA, Delladetsima JK. Overlap syndrome of primary sclerosing cholangitis and autoimmune hepatitis. Eur J Gastroenterol Hepatol. 2001;13:203–206.

    Article  CAS  PubMed  Google Scholar 

  32. Czaja AJ. Frequency and nature of the variant syndromes of autoimmune liver disease. Hepatology. 1998;28:360–365.

    Article  CAS  PubMed  Google Scholar 

  33. Rupp C, Mummelthei A, Sauer P, et al. Non-IBD immunological diseases are a risk factor for reduced survival in PSC. Liver Int. 2013;33:86–93.

    Article  CAS  PubMed  Google Scholar 

  34. Lüth S, Kanzler S, Frenzel C, et al. Characteristics and long-term prognosis of the autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. J Clin Gastroenterol. 2009;43:75–80.

    Article  PubMed  Google Scholar 

  35. Dang LJ, Lubel JS, Gunatheesan S, Hosking P, Su J. Drug-induced lupus and autoimmune hepatitis secondary to infliximab for psoriasis. Australas J Dermatol. 2014;55:75–79.

    Article  PubMed  Google Scholar 

  36. Yilmaz B, Roach EC, Koklu S. Infliximab leading to autoimmune hepatitis: an increasingly recognized side effect. Dig Dis Sci. 2014;59:2602–2603.

    Article  PubMed  Google Scholar 

  37. Doyle A, Forbes G, Kontorinis N. Autoimmune hepatitis during infliximab therapy for Crohn’s disease: a case report. J Crohns Colitis. 2011;5:253–255.

    Article  PubMed  Google Scholar 

  38. Goldfeld DA, Verna EC, Lefkowitch J, Swaminath A. Infliximab-induced autoimmune hepatitis with successful switch to adalimumab in a patient with Crohn’s disease: the index case. Dig Dis Sci. 2011;56:3386–3388.

    Article  PubMed  Google Scholar 

  39. Cravo M, Silva R, Serrano M. Autoimmune hepatitis induced by infliximab in a patient with Crohn’s disease with no relapse after switching to adalimumab. BioDrugs Clin Immunother Biopharm Gene Therapy. 2010;24:25–27.

    Article  Google Scholar 

  40. Van Casteren-Messidoro C, Prins G, van Tilburg A, Zelinkova Z, Schouten J, de Man R. Autoimmune hepatitis following treatment with infliximab for inflammatory bowel disease. J Crohns Colitis. 2012;6:630–631.

    Article  PubMed  Google Scholar 

  41. Subramaniam K, Chitturi S, Brown M, Pavli P. Infliximab-induced autoimmune hepatitis in Crohn’s disease treated with budesonide and mycophenolate. Inflamm Bowel Dis. 2011;17:E149–E150.

    Article  CAS  PubMed  Google Scholar 

  42. Ozorio G, McGarity B, Bak H, Jordan AS, Lau H, Marshall C. Autoimmune hepatitis following infliximab therapy for ankylosing spondylitis. Med J Aust. 2007;187:524–526.

    PubMed  Google Scholar 

  43. Marques M, Magro F, Cardoso H, et al. Infliximab-induced lupus-like syndrome associated with autoimmune hepatitis. Inflamm Bowel Dis. 2008;14:723–725.

    Article  CAS  PubMed  Google Scholar 

  44. Germano V, Picchianti Diamanti A, Baccano G, et al. Autoimmune hepatitis associated with infliximab in a patient with psoriatic arthritis. Ann Rheum Dis. 2005;64:1519–1520.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Fairhurst DA, Sheehan-Dare R. Autoimmune hepatitis associated with infliximab in a patient with palmoplantar pustular psoriasis. Clin Exp Dermatol. 2009;34:421–422.

    Article  CAS  PubMed  Google Scholar 

  46. Perez-Alvarez R, Pérez-de-Lis M, Ramos-Casals M. BIOGEAS study group: biologics-induced autoimmune diseases. Curr Opin Rheumatol. 2013;25:56–64.

    Article  CAS  PubMed  Google Scholar 

  47. Efe C. Drug induced autoimmune hepatitis and TNF-α blocking agents: is there a real relationship? Autoimmun Rev. 2013;12:337–339.

    Article  CAS  PubMed  Google Scholar 

  48. Harada K, Akai Y, Koyama S, Ikenaka Y, Saito Y. A case of autoimmune hepatitis exacerbated by the administration of etanercept in the patient with rheumatoid arthritis. Clin Rheumatol. 2008;27:1063–1066.

    Article  PubMed  Google Scholar 

  49. Parekh R, Kaur N. Liver injury secondary to anti-TNF-alpha therapy in inflammatory bowel disease: a case series and review of the literature. Case Rep Gastrointest Med. 2014;2014:1–5.

    Article  Google Scholar 

  50. Adar T, Mizrahi M, Pappo O, Scheiman-Elazary A, Shibolet O. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol. 2010;44:e20–e22.

    Article  PubMed  Google Scholar 

  51. Eriksson C, Engstrand S, Sundqvist K-G, Rantapää-Dahlqvist S. Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha. Ann Rheum Dis. 2005;64:403–407.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Tobon GJ, Cañas C, Jaller J-J, Restrepo J-C, Anaya J-M. Serious liver disease induced by infliximab. Clin Rheumatol. 2007;26:578–581.

    Article  PubMed  Google Scholar 

  53. Diehl AM. Cytokine regulation of liver injury and repair. Immunol Rev. 2000;174:160–171.

    Article  CAS  PubMed  Google Scholar 

  54. Rajanayagam J, Lewindon PJ. Infliximab as rescue therapy in paediatric autoimmune hepatitis. J Hepatol. 2013;59:908–909.

    Article  CAS  PubMed  Google Scholar 

  55. Vallejo Senra N, Fernández Castroagudín J, Molina Pérez E, Domínguez-Muñoz JE. Onset of severe acute autoimmune hepatitis refractory to conventional treatment, rescued with infliximab. Gastroenterol Hepatol. 2014. doi:10.1016/j.gastrohep.2014.02.012.

  56. Weiler-Normann C, Schramm C, Quaas A, et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol. 2013;58:529–534.

    Article  CAS  PubMed  Google Scholar 

  57. Diamantis I, Boumpas DT. Autoimmune hepatitis: evolving concepts. Autoimmun Rev. 2004;3:207–214.

    Article  CAS  PubMed  Google Scholar 

  58. Tanaka T, Sugawara Y, Kokudo N. Liver transplantation and autoimmune hepatitis. Intractable Rare Dis Res. 2015;4:33–38.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Seaberg EC, Belle SH, Beringer KC, Schivins JL, Detre KM. Liver transplantation in the United States from 1987–1998: updated results from the Pitt-UNOS Liver Transplant Registry. Clin Transpl. 1998;17–37.

  60. Molmenti EP, Netto GJ, Murray NG, et al. Incidence and recurrence of autoimmune/alloimmune hepatitis in liver transplant recipients. Liver Transplant. 2002;8:519–526.

    Article  Google Scholar 

  61. Lohse AW, Weiler-Norman C, Burdelski M. De novo autoimmune hepatitis after liver transplantation. Hepatol Res. 2007;37:S462.

    Article  PubMed  Google Scholar 

  62. Prados E, Cuervas-Mons V, de la Mata M, et al. Outcome of autoimmune hepatitis after liver transplantation. Transplantation. 1998;66:1645–1650.

    Article  CAS  PubMed  Google Scholar 

  63. Milkiewicz P, Hubscher SG, Skiba G, Hathaway M, Elias E. Recurrence of autoimmune hepatitis after liver transplantation. Transplantation. 1999;68:253–256.

    Article  CAS  PubMed  Google Scholar 

  64. Aguilera I, Sousa JM, Praena JM, Gómez-Bravo MA, Núñez-Roldan A. Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation. Clin Transplant. 2011;25:207–212.

    Article  CAS  PubMed  Google Scholar 

  65. Venick RS, McDiarmid SV, Farmer DG, et al. Rejection and steroid dependence: unique risk factors in the development of pediatric posttransplant de novo autoimmune hepatitis. Am J Transplant. 2007;7:955–963.

    Article  CAS  PubMed  Google Scholar 

  66. Salcedo M, Vaquero J, Bañares R, et al. Response to steroids in de novo autoimmune hepatitis after liver transplantation. Hepatology. 2002;35:349–356.

    Article  CAS  PubMed  Google Scholar 

  67. Kerkar N, Hadzić N, Davies ET, et al. De-novo autoimmune hepatitis after liver transplantation. Lancet. 1998;351:409–413.

    Article  CAS  PubMed  Google Scholar 

  68. Campsen J, Zimmerman MA, Trotter JF, et al. Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal. Liver Transplant. 2008;14:1281–1286.

    Article  Google Scholar 

  69. Sandhu A, Alameel T, Dale CH, Levstik M, Chande N. The safety and efficacy of antitumour necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series. Aliment Pharmacol Ther. 2012;36:159–165.

    Article  CAS  PubMed  Google Scholar 

  70. Verdonk RC, Dijkstra G, Haagsma EB, et al. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant. 2006;6:1422–1429.

    Article  CAS  PubMed  Google Scholar 

  71. Papatheodoridis GV, Hamilton M, Mistry PK, Davidson B, Rolles K, Burroughs AK. Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis. Gut.. 1998;43:639–644.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Riley TR, Schoen RE, Lee RG, Rakela J. A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease. Am J Gastroenterol. 1997;92:279–282.

    CAS  PubMed  Google Scholar 

  73. McDonald JWD, Feagan BG, Jewell DP, Brynskov J, Stange EF, Macdonald JK. Cyclosporine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2005. doi:10.1002/14651858.CD000297.pub2.

  74. Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005. doi:10.1002/14651858.CD004277.pub2.

  75. Benson A, Barrett T, Sparberg M, Buchman AL. Efficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn’s disease: a single-center experience. Inflamm Bowel Dis. 2008;14:7–12.

    Article  PubMed  Google Scholar 

  76. Fellermann K, Steffen M, Stein J, et al. Mycophenolate mofetil: lack of efficacy in chronic active inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14:171–176.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Gastroenterology and Hepatology, Weill Cornell Medical College/New York Presbyterian Hospital, 1305 York Avenue, 4th Floor, New York, NY, 10021, USA

    Ersilia M. DeFilippis & Sonal Kumar

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Correspondence to Sonal Kumar.

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DeFilippis, E.M., Kumar, S. Clinical Presentation and Outcomes of Autoimmune Hepatitis in Inflammatory Bowel Disease. Dig Dis Sci 60, 2873–2880 (2015). https://doi.org/10.1007/s10620-015-3699-4

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