Skip to main content
SpringerLink
Log in

Autoimmune hepatitis

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocytespecific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM. Diagnosis and management of autoimmune hepatitis. Hepatology 2010; 51(6): 2193–2213

    CAS  PubMed  Google Scholar 

  2. Strassburg CP. Autoimmune hepatitis. Dig Dis 2013; 31(1): 155–163

    PubMed  Google Scholar 

  3. Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. Lancet 2013; 382(9902): 1433–1444

    CAS  PubMed  Google Scholar 

  4. Ilyas JA, O’Mahony CA, Vierling JM. Liver transplantation in autoimmune liver diseases. Best Pract Res Clin Gastroenterol 2011; 25(6): 765–782

    PubMed  Google Scholar 

  5. Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology 2002; 36(2): 479–497

    PubMed  Google Scholar 

  6. Vierling JM. Diagnosis and treatment of autoimmune hepatitis. Curr Gastroenterol Rep 2012; 14(1): 25–36

    PubMed  Google Scholar 

  7. Boberg KM. Prevalence and epidemiology of autoimmune hepatitis. Clin Liver Dis 2002; 6(3): 635–647

    PubMed  Google Scholar 

  8. Primo J, Maroto N, Martínez M, Antón MD, Zaragoza A, Giner R, Devesa F, Merino C, del Olmo JA. Incidence of adult form of autoimmune hepatitis in Valencia (Spain). Acta Gastroenterol Belg 2009; 72(4): 402–406

    CAS  PubMed  Google Scholar 

  9. Delgado JS, Vodonos A, Malnick S, Kriger O, Wilkof-Segev R, Delgado B, Novack V, Rosenthal A, Menachem Y, Melzer E, Fich A. Autoimmune hepatitis in southern Israel: a 15-year multicenter study. J Dig Dis 2013; 14(11): 611–618

    CAS  PubMed  Google Scholar 

  10. Hurlburt KJ, McMahon BJ, Deubner H, Hsu-Trawinski B, Williams JL, Kowdley KV. Prevalence of autoimmune liver disease in Alaska Natives. Am J Gastroenterol 2002; 97(9): 2402–2407

    PubMed  Google Scholar 

  11. McFarlane IG. Autoimmune hepatitis: diagnostic criteria, subclassifications, and clinical features. Clin Liver Dis 2002; 6(3): 605–621

    PubMed  Google Scholar 

  12. Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, Mowat AP, Vergani D, Mieli-Vergani G. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25(3): 541–547

    CAS  PubMed  Google Scholar 

  13. Czaja AJ, Donaldson PT. Gender effects and synergisms with histocompatibility leukocyte antigens in type 1 autoimmune hepatitis. Am J Gastroenterol 2002; 97(8): 2051–2057

    CAS  PubMed  Google Scholar 

  14. Seki T, Ota M, Furuta S, Fukushima H, Kondo T, Hino K, Mizuki N, Ando A, Tsuji K, Inoko H, et al. HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients. Gastroenterology 1992; 103(3): 1041–1047

    CAS  PubMed  Google Scholar 

  15. Ngu JH, Bechly K, Chapman BA, Burt MJ, Barclay ML, Gearry RB, Stedman CA. Population-based epidemiology study of autoimmune hepatitis: a disease of older women? J Gastroenterol Hepatol 2010; 25(10): 1681–1686

    PubMed  Google Scholar 

  16. Czaja AJ. Autoimmune hepatitis in diverse ethnic populations and geographical regions. Expert Rev Gastroenterol Hepatol 2013; 7(4): 365–385

    CAS  PubMed  Google Scholar 

  17. Zolfino T, Heneghan MA, Norris S, Harrison PM, Portmann BC, McFarlane IG. Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin. Gut 2002; 50(5): 713–717

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Lim KN, Casanova RL, Boyer TD, Bruno CJ. Autoimmune hepatitis in African Americans: presenting features and response to therapy. Am J Gastroenterol 2001; 96(12): 3390–3394

    CAS  PubMed  Google Scholar 

  19. Verma S, Torbenson M, Thuluvath PJ. The impact of ethnicity on the natural history of autoimmune hepatitis. Hepatology 2007; 46(6): 1828–1835

    PubMed  Google Scholar 

  20. Nakamura K, Yoneda M, Yokohama S, Tamori K, Sato Y, Aso K, Aoshima M, Hasegawa T, Makino I. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J Gastroenterol Hepatol 1998; 13(5): 490–495

    CAS  PubMed  Google Scholar 

  21. Liberal R, Vergani D. Effect of ethnicity on the clinical presentation and outcome of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol 2012; 6(3): 267–269

    CAS  PubMed  Google Scholar 

  22. Peng M, Li Y, Zhang M, Jiang Y, Xu Y, Tian Y, Peng F, Gong G. Clinical features in different age groups of patients with autoimmune hepatitis. Exp Ther Med 2014; 7(1): 145–148

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Chen J, Eslick GD, Weltman M. Systematic review with metaanalysis: clinical manifestations and management of autoimmune hepatitis in the elderly. Aliment Pharmacol Ther 2014; 39(2): 117–124

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Liberal R, Grant CR, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: a comprehensive review. J Autoimmun 2013; 41: 126–139

    CAS  PubMed  Google Scholar 

  26. Ichiki Y, Aoki CA, Bowlus CL, Shimoda S, Ishibashi H, Gershwin ME. T cell immunity in autoimmune hepatitis. Autoimmun Rev 2005; 4(5): 315–321

    CAS  PubMed  Google Scholar 

  27. Vierling JM. The pathogenesis of autoimmune hepatitis. In: Hirschfield GM, Heathcote EJ. Autoimmune Hepatitis: A Guide for Practicing Clinicians. New York: Humana Press, 2012

    Google Scholar 

  28. Liberal R, Longhi MS, Mieli-Vergani G, Vergani D. Pathogenesis of autoimmune hepatitis. Best Pract Res Clin Gastroenterol 2011; 25(6): 653–664

    CAS  PubMed  Google Scholar 

  29. Czaja AJ. Drug-induced autoimmune-like hepatitis. Dig Dis Sci 2011; 56(4): 958–976

    CAS  PubMed  Google Scholar 

  30. Björnsson E, Talwalkar J, Treeprasertsuk S, Kamath PS, Takahashi N, Sanderson S, Neuhauser M, Lindor K. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology 2010; 51(6): 2040–2048

    PubMed  Google Scholar 

  31. Suzuki A, Brunt EM, Kleiner DE, Miquel R, Smyrk TC, Andrade RJ, Lucena MI, Castiella A, Lindor K, Björnsson E. The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology 2011; 54(3): 931–939

    PubMed Central  PubMed  Google Scholar 

  32. Lucena MI, Kaplowitz N, Hallal H, Castiella A, García-Bengoechea M, Otazua P, Berenguer M, Fernandez MC, Planas R, Andrade RJ. Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis. J Hepatol 2011; 55(4): 820–827

    CAS  PubMed  Google Scholar 

  33. Ju HY, Jang JY, Jeong SW, Woo SA, Kong MG, Jang HY, Lee SH, Kim SG, Cha SW, Kim YS, Cho YD, Jin SY, Kim HS, Kim BS. The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis. Clin Mol Hepatol 2012; 18(2): 213–218

    PubMed Central  PubMed  Google Scholar 

  34. de Boer YS, van Gerven NM, Zwiers A, Verwer BJ, van Hoek B, van Erpecum KJ, Beuers U, van Buuren HR, Drenth JP, den Ouden JW, Verdonk RC, Koek GH, Brouwer JT, Guichelaar MM, Vrolijk JM, Kraal G, Mulder CJ, van Nieuwkerk CM, Fischer J, Berg T, Stickel F, Sarrazin C, Schramm C, Lohse AW, Weiler-Normann C, Lerch MM, Nauck M, Völzke H, Homuth G, Bloemena E, Verspaget HW, Kumar V, Zhernakova A, Wijmenga C, Franke L, Bouma G. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1. Gastroenterology 2014; 147(2): 443–452, e5

    PubMed  Google Scholar 

  35. Duarte-Rey C, Pardo AL, Rodríguez-Velosa Y, Mantilla RD, Anaya JM, Rojas-Villarraga A. HLA class II association with autoimmune hepatitis in Latin America: a meta-analysis. Autoimmun Rev 2009; 8(4): 325–331

    CAS  PubMed  Google Scholar 

  36. Longhi MS, Ma Y, Grant CR, Samyn M, Gordon P, Mieli-Vergani G, Vergani D. T-regs in autoimmune hepatitis-systemic lupus erythematosus/mixed connective tissue disease overlap syndrome are functionally defective and display a Th1 cytokine profile. J Autoimmun 2013; 41: 146–151

    CAS  PubMed  Google Scholar 

  37. Muratori L, Longhi MS. The interplay between regulatory and effector T cells in autoimmune hepatitis: Implications for innovative treatment strategies. J Autoimmun 2013; 46: 74–80

    CAS  PubMed  Google Scholar 

  38. Grant CR, Liberal R, Holder BS, Cardone J, Ma Y, Robson SC, Mieli-Vergani G, Vergani D, Longhi MS. Dysfunctional CD39 (POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis. Hepatology 2014; 59(3): 1007–1015

    CAS  PubMed  Google Scholar 

  39. Peiseler M, Sebode M, Franke B, Wortmann F, Schwinge D, Quaas A, Baron U, Olek S, Wiegard C, Lohse AW, Weiler-Normann C, Schramm C, Herkel J. FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency. J Hepatol 2012; 57(1): 125–132

    CAS  PubMed  Google Scholar 

  40. Vierling JM. Autoimmune hepatitis and antigen-specific T regulatory cells: when can we send in the regulators? Hepatology 2011; 53(2): 385–388

    CAS  PubMed  Google Scholar 

  41. Stravitz RT, Lefkowitch JH, Fontana RJ, Gershwin ME, Leung PS, Sterling RK, Manns MP, Norman GL, Lee WM. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011; 53(2): 517–526

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Tanaka A. Acute presentation of autoimmune hepatitis: how to find and manage still remains unsolved. Hepatol Res 2013; 43(6): 577–579

    PubMed  Google Scholar 

  43. Czaja AJ. Acute and acute severe (fulminant) autoimmune hepatitis. Dig Dis Sci 2013; 58(4): 897–914

    CAS  PubMed  Google Scholar 

  44. Scott J, Gollan JL, Samourian S, Sherlock S. Wilson’s disease, presenting as chronic active hepatitis. Gastroenterology 1978; 74(4): 645–651

    CAS  PubMed  Google Scholar 

  45. Milkiewicz P, Saksena S, Hubscher SG, Elias E. Wilson’s disease with superimposed autoimmune features: report of two cases and review. J Gastroenterol Hepatol 2000; 15(5): 570–574

    CAS  PubMed  Google Scholar 

  46. Deutsch M, Emmanuel T, Koskinas J. Autoimmune hepatitis or Wilson’s disease, a clinical dilemma. Hepat Mon 2013; 13(5): e7872

    PubMed Central  PubMed  Google Scholar 

  47. Santos RG, Alissa F, Reyes J, Teot L, Ameen N. Fulminant hepatic failure:Wilson’s disease or autoimmune hepatitis? Implications for transplantation. Pediatr Transplant 2005; 9(1): 112–116

    CAS  PubMed  Google Scholar 

  48. Kaymakoğlu S. Drug-induced hepatitis, drug-induced autoimmunity or classical autoimmune hepatitis: how can we differentiate? Turk J Gastroenterol 2004; 15(3): 123–125

    PubMed  Google Scholar 

  49. Fujiwara K, Yokosuka O. Histological discrimination between autoimmune hepatitis and drug-induced liver injury. Hepatology 2012; 55(2): 657

    PubMed  Google Scholar 

  50. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, Donaldson PT, Eddleston AL, Fainboim L, Heathcote J, Homberg JC, Hoofnagle JH, Kakumu S, Krawitt EL, Mackay IR, MacSween RN, Maddrey WC, Manns MP, McFarlane IG, Meyer zum Büschenfelde KH, Zeniya M, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999; 31(5): 929–938

    CAS  PubMed  Google Scholar 

  51. Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL, Bittencourt PL, Porta G, Boberg KM, Hofer H, Bianchi FB, Shibata M, Schramm C, Eisenmann de Torres B, Galle PR, McFarlane I, Dienes HP, Lohse AW. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 2008; 48(1): 169–176

    PubMed  Google Scholar 

  52. Liberal R, Grant CR, Longhi MS, Mieli-Vergani G, Vergani D. Diagnostic criteria of autoimmune hepatitis. Autoimmun Rev 2014; 13(4–5): 435–440

    CAS  PubMed  Google Scholar 

  53. Gatselis NK, Zachou K, Papamichalis P, Koukoulis GK, Gabeta S, Dalekos GN, Rigopoulou EI. Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: a new or a complementary diagnostic score? Dig Liver Dis 2010; 42(11): 807–812

    PubMed  Google Scholar 

  54. Czaja AJ. Comparability of probable and definite autoimmune hepatitis by international diagnostic scoring criteria. Gastroenterology 2011; 140(5): 1472–1480

    PubMed  Google Scholar 

  55. Abdollahi MR, Somi MH, Faraji E. Role of international criteria in the diagnosis of autoimmune hepatitis. World J Gastroenterol 2013; 19(23): 3629–3633

    PubMed Central  PubMed  Google Scholar 

  56. Li Y, Peng M, Gong G. Evaluation of the revised versus the simplified scoring system in patients with autoimmune hepatitis. Exp Ther Med 2014; 7(1): 131–136

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Qiu D, Wang Q, Wang H, Xie Q, Zang G, Jiang H, Tu C, Guo J, Zhang S, Wang J, Lu Y, Han Y, Shen L, Chen X, Hu X, Wang X, Chen C, Fu Q, Ma X. Validation of the simplified criteria for diagnosis of autoimmune hepatitis in Chinese patients. J Hepatol 2011; 54(2): 340–347

    PubMed  Google Scholar 

  58. Lohse AW. Recognizing autoimmune hepatitis: scores help, but no more. J Hepatol 2011; 54(2): 193–194

    PubMed  Google Scholar 

  59. Wang QX, Jiang WJ, Miao Q, Xiao X, Zhang HY, Huang SS, Shen L, Hua J, Li H, Li S, Qiu K, Ma X. Clinical and histological features of autoantibody-negative autoimmune hepatitis in Chinese patients: a single center experience. J Dig Dis 2013; 14(4): 175–180

    CAS  PubMed  Google Scholar 

  60. Czaja AJ. The overlap syndromes of autoimmune hepatitis. Dig Dis Sci 2013; 58(2): 326–343

    CAS  PubMed  Google Scholar 

  61. Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol 2011; 54(2): 374–385

    PubMed  Google Scholar 

  62. Krawitt EL. Discrimination of autoimmune hepatitis: autoantibody typing and beyond. J Gastroenterol 2011; 46(S1): 39–41

    CAS  PubMed  Google Scholar 

  63. Couto CA, Bittencourt PL, Porta G, Abrantes-Lemos CP, Carrilho FJ, Guardia BD, Cançado EL. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis. Hepatology 2014; 59(2): 592–600

    CAS  PubMed  Google Scholar 

  64. Czaja AJ. Autoantibody-negative autoimmune hepatitis. Dig Dis Sci 2012; 57(3): 610–624

    CAS  PubMed  Google Scholar 

  65. Czaja AJ. Performance parameters of the conventional serological markers for autoimmune hepatitis. Dig Dis Sci 2011; 56(2): 545–554

    CAS  PubMed  Google Scholar 

  66. Vergani D, Alvarez F, Bianchi FB, Cançado EL, Mackay IR, Manns MP, Nishioka M, Penner E. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 2004; 41(4): 677–683

    PubMed  Google Scholar 

  67. Liu H, Norman GL, Shums Z, Worman HJ, Krawitt EL, Bizzaro N, Vergani D, Bogdanos DP, Dalekos GN, Milkiewicz P, Czaja AJ, Heathcote EJ, Hirschfield GM, Tan EM, Miyachi K, Bignotto M, Battezzati PM, Lleo A, Leung PS, Podda M, Gershwin ME, Invernizzi P. PBC screen: an IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J Autoimmun 2010; 35(4): 436–442

    CAS  PubMed  Google Scholar 

  68. Czaja AJ. Autoantibodies as prognostic markers in autoimmune liver disease. Dig Dis Sci 2010; 55(8): 2144–2161

    CAS  PubMed  Google Scholar 

  69. Oikonomou KG, Zachou K, Dalekos GN. Alpha-actinin: a multidisciplinary protein with important role in B-cell driven autoimmunity. Autoimmun Rev 2011; 10(7): 389–396

    CAS  PubMed  Google Scholar 

  70. Kanno Y, Watanabe H, Takahashi A, Abe K, Ohira H. Antiphosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis. Hepatol Res 2014; 44(9): 1019–1025

    CAS  PubMed  Google Scholar 

  71. Calich AL, Viana VS, Cancado E, Tustumi F, Terrabuio DR, Leon EP, Silva CA, Borba EF, Bonfa E. Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis. Liver Int 2013; 33(6): 909–913

    PubMed  Google Scholar 

  72. Yokokawa J, Kanno Y, Abe K, Saito H, Monoe K, Katsushima F, Sakamoto N, Takahashi A, Yokokawa H, Ohira H. Antinucleosome autoantibodies as markers for autoimmune hepatitis and their correlation with disease activity. Hepatol Res 2013 [Epub ahead of print] doi: 10.1111/hepr.12130

    Google Scholar 

  73. Matsumoto K, Miyake Y, Matsushita H, Ohnishi A, Ikeda F, Shiraha H, Takaki A, Nouso K, Yamamoto K. Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis. J Gastroenterol Hepatol 2014; 29(1): 110–115

    CAS  PubMed  Google Scholar 

  74. Zingaretti C, Arigò M, Cardaci A, Moro M, Crosti M, Sinisi A, Sugliano E, Cheroni C, Marabita F, Nogarotto R, Bonnal RJ, Marcatili P, Marconi M, Zignego A, Muratori P, Invernizzi P, Colombatto P, Brunetto M, Bonino F, De Francesco R, Geginat J, Pagani M, Muratori L, Abrignani S, Bombaci M. Identification of new autoantigens by protein array indicates a role for IL4 neutralization in autoimmune hepatitis. Mol Cell Proteomics 2012; 11(12): 1885–1897

    PubMed Central  PubMed  Google Scholar 

  75. Guindi M. Histology of autoimmune hepatitis and its variants. Clin Liver Dis 2010; 14(4): 577–590

    PubMed  Google Scholar 

  76. Efe C, Wahlin S, Ozaslan E, Purnak T, Muratori L, Quarneti C, Tatar G, Simsek H, Muratori P, Schiano TD. Diagnostic difficulties, therapeutic strategies, and performance of scoring systems in patients with autoimmune hepatitis and concurrent hepatitis B/C. Scand J Gastroenterol 2013; 48(4): 504–508

    PubMed  Google Scholar 

  77. Pischke S, Gisa A, Suneetha PV, Wiegand SB, Taubert R, Schlue J, Wursthorn K, Bantel H, Raupach R, Bremer B, Zacher BJ, Schmidt RE, Manns MP, Rifai K, Witte T, Wedemeyer H. Increased HEV seroprevalence in patients with autoimmune hepatitis. PLoS ONE 2014; 9(1): e85330

    PubMed Central  PubMed  Google Scholar 

  78. Te HS, Koukoulis G, Ganger DR. Autoimmune hepatitis: a histological variant associated with prominent centrilobular necrosis. Gut 1997; 41(2): 269–271

    CAS  PubMed  Google Scholar 

  79. Hofer H, Oesterreicher C, Wrba F, Ferenci P, Penner E. Centrilobular necrosis in autoimmune hepatitis: a histological feature associated with acute clinical presentation. J Clin Pathol 2006; 59(3): 246–249

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Björnsson E, Talwalkar J, Treeprasertsuk S, Neuhauser M, Lindor K. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol 2011; 9(1): 57–63

    PubMed  Google Scholar 

  81. Yasui S, Fujiwara K, Yonemitsu Y, Oda S, Nakano M, Yokosuka O. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol 2011; 46(3): 378–390

    PubMed  Google Scholar 

  82. Czaja AJ. Corticosteroids or not in severe acute or fulminant autoimmune hepatitis: therapeutic brinksmanship and the point beyond salvation. Liver Transpl 2007; 13(7): 953–955

    PubMed  Google Scholar 

  83. Ichai P, Duclos-Vallée JC, Guettier C, Hamida SB, Antonini T, Delvart V, Saliba F, Azoulay D, Castaing D, Samuel D. Usefulness of corticosteroids for the treatment of severe and fulminant forms of autoimmune hepatitis. Liver Transpl 2007; 13(7): 996–1003

    PubMed  Google Scholar 

  84. Kessler WR, Cummings OW, Eckert G, Chalasani N, Lumeng L, Kwo PY. Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis. Clin Gastroenterol Hepatol 2004; 2(7): 625–631

    PubMed  Google Scholar 

  85. Verma S, Maheshwari A, Thuluvath P. Liver failure as initial presentation of autoimmune hepatitis: clinical characteristics, predictors of response to steroid therapy, and outcomes. Hepatology 2009; 49(4): 1396–1397

    PubMed  Google Scholar 

  86. Villamil AG, Casciato P, Eduardo M, et al. Fulminant autoimmune hepatitis type 1: clinical presentation, outcome and prognostic factors(Abstract 480). AJT 5(suppl 11): 2011

  87. Efe C, Ozaslan E, Nasiroglu N, Tunca H, Purnak T, Altiparmak E. The development of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome during the course of connective tissue diseases: report of three cases and review of the literature. Dig Dis Sci 2010; 55(8): 2417–2421

    PubMed  Google Scholar 

  88. Loria P, Lonardo A, Leonardi F, Fontana C, Carulli L, Verrone AM, Borsatti A, Bertolotti M, Cassani F, Bagni A, Muratori P, Ganazzi D, Bianchi FB, Carulli N. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci 2003; 48(11): 2173–2181

    PubMed  Google Scholar 

  89. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2004; 38(9): 801–804

    PubMed  Google Scholar 

  90. Badiani RG, Becker V, Perez RM, Matos CA, Lemos LB, Lanzoni VP, Andrade LE, Dellavance A, Silva AE, Ferraz ML. Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis? World J Gastroenterol 2010; 16(29): 3704–3708

    PubMed Central  PubMed  Google Scholar 

  91. Zellos A, Boitnott JK, Schwarz KB. New-onset autoimmune hepatitis in young patients with preexisting liver disease. Dig Liver Dis 2010; 42(9): 657–660

    PubMed  Google Scholar 

  92. Unzueta A, Rakela J. Hepatitis E infection in liver transplant recipients. Liver Transpl 2014; 20(1): 15–24

    PubMed  Google Scholar 

  93. Moal V, Legris T, Burtey S, Morange S, Purgus R, Dussol B, Garcia S, Motte A, Gérolami R, Berland Y, Colson P. Infection with hepatitis E virus in kidney transplant recipients in southeastern France. J Med Virol 2013; 85(3): 462–471

    PubMed  Google Scholar 

  94. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53(3): 1020–1022

    PubMed Central  PubMed  Google Scholar 

  95. Sherman M, Bruix J, Porayko M, Tran T. Screening for hepatocellular carcinoma: the rationale for the American Association for the Study of Liver Diseases recommendations. Hepatology 2012; 56(3): 793–796

    PubMed  Google Scholar 

  96. Czaja AJ. Hepatocellular carcinoma and other malignancies in autoimmune hepatitis. Dig Dis Sci 2013; 58(6): 1459–1476

    CAS  PubMed  Google Scholar 

  97. Ohira H, Abe K, Takahashi A, Zeniya M, Ichida T. Clinical features of hepatocellular carcinoma in patients with autoimmune hepatitis in Japan. J Gastroenterol 2013; 48(1): 109–114

    PubMed  Google Scholar 

  98. Yeoman AD, Al-Chalabi T, Karani JB, Quaglia A, Devlin J, Mieli-Vergani G, Bomford A, O’Grady JG, Harrison PM, Heneghan MA. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: implications for follow-up and screening. Hepatology 2008; 48(3): 863–870

    PubMed  Google Scholar 

  99. Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12(9): 1430–1438

    CAS  PubMed  Google Scholar 

  100. Czaja AJ. Diagnosis and management of the overlap syndromes of autoimmune hepatitis. Can J Gastroenterol 2013; 27(7): 417–423

    PubMed Central  PubMed  Google Scholar 

  101. Gossard AA, Lindor KD. Development of autoimmune hepatitis in primary biliary cirrhosis. Liver Int 2007; 27(8): 1086–1090

    PubMed  Google Scholar 

  102. Czaja AJ. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a foray across diagnostic boundaries. J Hepatol 2006; 44(2): 251–252

    PubMed  Google Scholar 

  103. Neuhauser M, Bjornsson E, Treeprasertsuk S, Enders F, Silveira M, Talwalkar J, Lindor K. Autoimmune hepatitis-PBC overlap syndrome: a simplified scoring system may assist in the diagnosis. Am J Gastroenterol 2010; 105(2): 345–353

    CAS  PubMed  Google Scholar 

  104. Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 1998; 28(2): 296–301

    PubMed  Google Scholar 

  105. Kuiper EM, Zondervan PE, van Buuren HR. Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome. Clin Gastroenterol Hepatol 2010; 8(6): 530–534

    PubMed  Google Scholar 

  106. Yokokawa J, Saito H, Kanno Y, Honma F, Monoe K, Sakamoto N, Abe K, Takahashi A, Yokokawa H, Ohira H. Overlap of primary biliary cirrhosis and autoimmune hepatitis: characteristics, therapy, and long term outcomes. J Gastroenterol Hepatol 2010; 25(2): 376–382

    CAS  PubMed  Google Scholar 

  107. Heurgué A, Vitry F, Diebold MD, Yaziji N, Bernard-Chabert B, Pennaforte JL, Picot R, Louvet H, Frémond L, Geoffroy P, Schmit JL, Cadiot G, Thiéfin G. Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis: a retrospective study of 115 cases of autoimmune liver disease. Gastroenterol Clin Biol 2007; 31(1): 17–25

    PubMed  Google Scholar 

  108. Yoshioka Y, Taniai M, Hashimoto E, Haruta I, Shiratori K. Clinical profile of primary biliary cirrhosis with features of autoimmune hepatitis: importance of corticosteroid therapy. Hepatol Res 2014; 44(9): 947–955

    CAS  PubMed  Google Scholar 

  109. Ozaslan E, Efe C, Akbulut S, Purnak T, Savas B, Erden E, Altiparmak E. Therapy response and outcome of overlap syndromes: autoimmune hepatitis and primary biliary cirrhosis compared to autoimmune hepatitis and autoimmune cholangitis. Hepatogastroenterology 2010; 57(99–100): 441–446

    PubMed  Google Scholar 

  110. Silveira MG, Talwalkar JA, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes. Am J Gastroenterol 2007; 102(6): 1244–1250

    PubMed  Google Scholar 

  111. Efe C, Wahlin S, Ozaslan E, Berlot AH, Purnak T, Muratori L, Quarneti C, Yüksel O, Thiéfin G, Muratori P. Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases. Eur J Gastroenterol Hepatol 2012; 24(5): 531–534

    PubMed  Google Scholar 

  112. Coss Adame E, Granados J, Uribe M, Torre A. Does HLA-DR7 differentiate the overlap syndrome of auto-immune hepatitisprimary biliary cirrhosis (AIH-PBC) from those with auto-immune hepatitis type 1? Ann Hepatol 2011; 10(1): 28–32

    PubMed  Google Scholar 

  113. Levy C, Naik J, Giordano C, Mandalia A, O’Brien C, Bhamidimarri KR, Schiff ER, Martin P. Hispanics with primary biliary cirrhosis are more likely to have features of autoimmune hepatitis and reduced response to ursodeoxycholic acid than non-Hispanics. Clin Gastroenterol Hepatol 2014; 12(8): 1398–1405

    CAS  PubMed  Google Scholar 

  114. Lee H, Stapp RT, Ormsby AH, Shah VV. The usefulness of IgG and IgM immunostaining of periportal inflammatory cells (plasma cells and lymphocytes) for the distinction of autoimmune hepatitis and primary biliary cirrhosis and their staining pattern in autoimmune hepatitis-primary biliary cirrhosis overlap syndrome. Am J Clin Pathol 2010; 133(3): 430–437

    PubMed  Google Scholar 

  115. Cabibi D, Tarantino G, Barbaria F, Campione M, CraxÌ A, Di Marco V. Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver diseases. Dig Liver Dis 2010; 42(8): 585–592

    CAS  PubMed  Google Scholar 

  116. Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol 2000; 33(4): 537–542

    CAS  PubMed  Google Scholar 

  117. Hunter M, Loughrey MB, Gray M, Ellis P, McDougall N, Callender M. Evaluating distinctive features for early diagnosis of primary sclerosing cholangitis overlap syndrome in adults with autoimmune hepatitis. Ulster Med J 2011; 80(1): 15–18

    PubMed Central  PubMed  Google Scholar 

  118. Floreani A, Rizzotto ER, Ferrara F, Carderi I, Caroli D, Blasone L, Baldo V. Clinical course and outcome of autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Am J Gastroenterol 2005; 100(7): 1516–1522

    PubMed  Google Scholar 

  119. Czaja AJ. Variant forms of autoimmune hepatitis. Curr Gastroenterol Rep 1999; 1(1): 63–70

    CAS  PubMed  Google Scholar 

  120. Czaja AJ. Review article: the management of autoimmune hepatitis beyond consensus guidelines. Aliment Pharmacol Ther 2013; 38(4): 343–364

    CAS  PubMed  Google Scholar 

  121. Culver EL, Chapman RW. Systematic review: management options for primary sclerosing cholangitis and its variant forms-IgG4-associated cholangitis and overlap with autoimmune hepatitis. Aliment Pharmacol Ther 2011; 33(12): 1273–1291

    CAS  PubMed  Google Scholar 

  122. Umemura T, Zen Y, Hamano H, Joshita S, Ichijo T, Yoshizawa K, Kiyosawa K, Ota M, Kawa S, Nakanuma Y, Tanaka E. Clinical significance of immunoglobulin G4-associated autoimmune hepatitis. J Gastroenterol 2011; 46(S1 Suppl 1): 48–55

    CAS  PubMed  Google Scholar 

  123. Peedikayil MC, Dahhan TI, Al Ashgar HI. Nitrofurantoin-induced fulminant hepatitis mimicking autoimmune hepatitis. Ann Pharmacother 2006; 40(10): 1888–1889

    PubMed  Google Scholar 

  124. Alla V, Abraham J, Siddiqui J, Raina D, Wu GY, Chalasani NP, Bonkovsky HL. Autoimmune hepatitis triggered by statins. J Clin Gastroenterol 2006; 40(8): 757–761

    CAS  PubMed  Google Scholar 

  125. von Felden J, Montani M, Kessebohm K, Stickel F. Drug-induced acute liver injury mimicking autoimmune hepatitis after intake of dietary supplements containing glucosamine and chondroitin sulfate. Int J Clin Pharmacol Ther 2013; 51(3): 219–223

    Google Scholar 

  126. Oh HJ, Mok YM, Baek MS, Lee JK, Seo BS, Kim TH, Choi KH, Hwang IK, Ra JE, Oh YR, Kim YS, Cho EY, Kim HC, Sohn YW. Co-development of autoimmune hepatitis and Sjögren’s syndrome triggered by the administration of herbal medicines. Clin Mol Hepatol 2013; 19(3): 305–308

    PubMed Central  PubMed  Google Scholar 

  127. Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 2011; 89(6): 806–815

    CAS  PubMed  Google Scholar 

  128. Yeoman AD, Westbrook RH, Zen Y, Maninchedda P, Portmann BC, Devlin J, O’Grady JG, Harrison PM, Heneghan MA. Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis. Hepatology 2011; 53(3): 926–934

    PubMed  Google Scholar 

  129. Muratori L, Muratori P, Lanzoni G, Ferri S, Lenzi M. Application of the 2010 American Association for the study of liver diseases criteria of remission to a cohort of Italian patients with autoimmune hepatitis. Hepatology 2010; 52(5): 1857–1858, author reply 1857–1858

    PubMed  Google Scholar 

  130. Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Günther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Färkkilä M, Pröls M, Strassburg CP. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology 2010; 139(4): 1198–1206

    CAS  PubMed  Google Scholar 

  131. Lamers MM, van Oijen MG, Pronk M, Drenth JP. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol 2010; 53(1): 191–198

    CAS  PubMed  Google Scholar 

  132. Czaja AJ. Drug choices in autoimmune hepatitis: part A-steroids. Expert Rev Gastroenterol Hepatol 2012; 6(5): 603–615

    CAS  PubMed  Google Scholar 

  133. Strassburg CP. Therapeutic options to treat autoimmune hepatitis in 2009. Dig Dis 2010; 28(1): 93–98

    PubMed  Google Scholar 

  134. Geier A, Gartung C, Dietrich CG, Wasmuth HE, Reinartz P, Matern S. Side effects of budesonide in liver cirrhosis due to chronic autoimmune hepatitis: influence of hepatic metabolism versus portosystemic shunts on a patient complicated with HCC. World J Gastroenterol 2003; 9(12): 2681–2685

    PubMed  Google Scholar 

  135. Lohse AW, Gil H. Reactivation of autoimmune hepatitis during budesonide monotherapy, and response to standard treatment. J Hepatol 2011; 54(4): 837–839

    PubMed  Google Scholar 

  136. van Gerven NM, Verwer BJ, Witte BI, van Hoek B, Coenraad MJ, van Erpecum KJ, Beuers U, van Buuren HR, de Man RA, Drenth JP, den Ouden JW, Verdonk RC, Koek GH, Brouwer JT, Guichelaar MM, Mulder CJ, van Nieuwkerk KM, Bouma G. Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission. J Hepatol 2013; 58(1): 141–147

    PubMed  Google Scholar 

  137. Czaja AJ. Review article: permanent drug withdrawal is desirable and achievable for autoimmune hepatitis. Aliment Pharmacol Ther 2014; 39(10): 1043–1058

    CAS  PubMed  Google Scholar 

  138. Montano-Loza AJ, Carpenter HA, Czaja AJ. Consequences of treatment withdrawal in type 1 autoimmune hepatitis. Liver Int 2007; 27(4): 507–515

    CAS  PubMed  Google Scholar 

  139. Czaja AJ, Carpenter HA. Thiopurine methyltransferase deficiency and azathioprine intolerance in autoimmune hepatitis. Dig Dis Sci 2006; 51(5): 968–975

    CAS  PubMed  Google Scholar 

  140. Gisbert JP, Gomollón F, Cara C, Luna M, González-Lama Y, Pajares JM, Maté J, Guijarro LG. Thiopurine methyltransferase activity in Spain: a study of 14,545 patients. Dig Dis Sci 2007; 52(5): 1262–1269

    CAS  PubMed  Google Scholar 

  141. Heneghan MA, Allan ML, Bornstein JD, Muir AJ, Tendler DA. Utility of thiopurine methyltransferase genotyping and phenotyping, and measurement of azathioprine metabolites in the management of patients with autoimmune hepatitis. J Hepatol 2006; 45(4): 584–591

    CAS  PubMed  Google Scholar 

  142. Heneghan MA, Allan ML, Bornstein JD, Muir AJ, Tendler DA. Utility of thiopurine methyltransferase genotyping and phenotyping, and measurement of azathioprine metabolites in the management of patients with autoimmune hepatitis. J Hepatol 2006; 45(4): 584–591

    CAS  PubMed  Google Scholar 

  143. Nguyen TM, Daubard M, Le Gall C, Larger M, Lachaux A, Boulieu R. Monitoring of azathioprine metabolites in pediatric patients with autoimmune hepatitis. Ther Drug Monit 2010; 32(4): 433–437

    CAS  PubMed  Google Scholar 

  144. Hindorf U, Jahed K, Bergquist A, Verbaan H, Prytz H, Wallerstedt S, Werner M, Olsson R, Björnsson E, Peterson C, Almer SH. Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis. J Hepatol 2010; 52(1): 106–111

    CAS  PubMed  Google Scholar 

  145. de Boer YS, van Gerven NM, de Boer NK, Mulder CJ, Bouma G, van Nieuwkerk CM. Allopurinol safely and effectively optimises thiopurine metabolites in patients with autoimmune hepatitis. Aliment Pharmacol Ther 2013; 37(6): 640–646

    PubMed  Google Scholar 

  146. Ferucci ED, Hurlburt KJ, Mayo MJ, Livingston S, Deubner H, Gove J, Plotnik J, McMahon BJ. Azathioprine metabolite measurements are not useful in following treatment of autoimmune hepatitis in Alaska Native and other non-Caucasian people. Can J Gastroenterol 2011; 25(1): 21–27

    PubMed Central  PubMed  Google Scholar 

  147. Jothimani D, Cramp ME, Mitchell JD, Cross TJ. Treatment of autoimmune hepatitis: a review of current and evolving therapies. J Gastroenterol Hepatol 2011; 26(4): 619–627

    CAS  PubMed  Google Scholar 

  148. Wang SB, Wang JH, Zheng RH, Zhong BH, Chen MH. Deep cholestatic jaundice as the predominant manifestation in autoimmune hepatitis. Hepatogastroenterology 2010; 57(98): 326–329

    PubMed  Google Scholar 

  149. Roll J, Boyer JL, Barry D, Klatskin G. The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis. N Engl J Med 1983; 308(1): 1–7

    CAS  PubMed  Google Scholar 

  150. Christensen E, Neuberger J, Crowe J, Altman DG, Popper H, Portmann B, Doniach D, Ranek L, Tygstrup N, Williams R. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial. Gastroenterology 1985; 89(5): 1084–1091

    CAS  PubMed  Google Scholar 

  151. Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. J Hepatol 1992; 15(3): 336–344

    CAS  PubMed  Google Scholar 

  152. Heathcote J, Ross A, Sherlock S. A prospective controlled trial of azathioprine in primary biliary cirrhosis. Gastroenterology 1976; 70(5 PT.1): 656–660

    CAS  PubMed  Google Scholar 

  153. Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig Dis Sci 2009; 54(11): 2519–2522

    CAS  PubMed  Google Scholar 

  154. Baven-Pronk AM, Coenraad MJ, van Buuren HR, de Man RA, van Erpecum KJ, Lamers MM, Drenth JP, van den Berg AP, Beuers UH, den Ouden J, Koek GH, van Nieuwkerk CM, Bouma G, Brouwer JT, van Hoek B. The role of mycophenolate mofetil in the management of autoimmune hepatitis and overlap syndromes. Aliment Pharmacol Ther 2011; 34(3): 335–343

    CAS  PubMed  Google Scholar 

  155. Schramm C, Herkel J, Beuers U, Kanzler S, Galle PR, Lohse AW. Pregnancy in autoimmune hepatitis: outcome and risk factors. Am J Gastroenterol 2006; 101(3): 556–560

    CAS  PubMed  Google Scholar 

  156. Werner M, Björnsson E, Prytz H, Lindgren S, Almer S, Broomé U, Wallerstedt S, Sandberg-Gertzén H, Hultcrantz R, Sangfeldt P, Nilsson J, Danielsson A. Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding? Scand J Gastroenterol 2007; 42(8): 986–991

    PubMed  Google Scholar 

  157. Westbrook RH, Yeoman AD, Kriese S, Heneghan MA. Outcomes of pregnancy in women with autoimmune hepatitis. J Autoimmun 2012; 38(2–3): J239–J244

    PubMed  Google Scholar 

  158. Terrabuio DR, Abrantes-Lemos CP, Carrilho FJ, Cançado EL. Follow-up of pregnant women with autoimmune hepatitis: the disease behavior along with maternal and fetal outcomes. J Clin Gastroenterol 2009; 43(4): 350–356

    PubMed  Google Scholar 

  159. de Boer NK, Jarbandhan SV, de Graaf P, Mulder CJ, van Elburg RM, van Bodegraven AA. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am J Gastroenterol 2006; 101(6): 1390–1392

    PubMed  Google Scholar 

  160. Muratori P, Loffreda S, Muratori L, Ferrari R, Afandi K, Cassani F, Pappas G, Lenzi M, Bianchi FB. Spontaneous remission of autoimmune hepatitis during pregnancy. Dig Liver Dis 2002; 34(8): 608–609

    CAS  PubMed  Google Scholar 

  161. Samuel D, Riordan S, Strasser S, Kurtovic J, Singh-Grewel I, Koorey D. Severe autoimmune hepatitis first presenting in the early post partum period. Clin Gastroenterol Hepatol 2004; 2(7): 622–624

    PubMed  Google Scholar 

  162. Strassburg CP. Autoimmune hepatitis: new guidelines, new therapies. Dig Dis 2012; 30(S1): 11–19

    PubMed  Google Scholar 

  163. Czaja AJ. Current and future treatments of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol 2009; 3(3): 269–291

    CAS  PubMed  Google Scholar 

  164. Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology 2010; 139(1): 58–72, e4

    CAS  PubMed  Google Scholar 

  165. Czaja AJ. Difficult treatment decisions in autoimmune hepatitis. World J Gastroenterol 2010; 16(8): 934–947

    PubMed Central  CAS  PubMed  Google Scholar 

  166. Mayo MJ. Management of autoimmune hepatitis. Curr Opin Gastroenterol 2011; 27(3): 224–230

    CAS  PubMed  Google Scholar 

  167. Yeoman AD, Longhi MS, Heneghan MA. Review article: the modern management of autoimmune hepatitis. Aliment Pharmacol Ther 2010; 31(8): 771–787

    CAS  PubMed  Google Scholar 

  168. Vergani D, Mieli-Vergani G. Pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother 2011; 12(4): 607–613

    PubMed  Google Scholar 

  169. Czaja AJ. Drug choices in autoimmune hepatitis: part B-Nonsteroids. Expert Rev Gastroenterol Hepatol 2012; 6(5): 617–635

    CAS  PubMed  Google Scholar 

  170. Selvarajah V, Montano-Loza AJ, Czaja AJ. Systematic review: managing suboptimal treatment responses in autoimmune hepatitis with conventional and nonstandard drugs. Aliment Pharmacol Ther 2012; 36(8): 691–707

    CAS  PubMed  Google Scholar 

  171. Czaja AJ. Nonstandard drugs and feasible new interventions for autoimmune hepatitis: part I. Inflamm Allergy Drug Targets 2012; 11(5): 337–350

    CAS  PubMed  Google Scholar 

  172. D’Agostino D, Costaguta A, Álvarez F. Successful treatment of refractory autoimmune hepatitis with rituximab. Pediatrics 2013; 132(2): e526–e530

    PubMed  Google Scholar 

  173. Burak KW, Swain MG, Santodomingo-Garzon T, Lee SS, Urbanski SJ, Aspinall AI, Coffin CS, Myers RP. Rituximab for the treatment of patients with autoimmune hepatitis who are refractory or intolerant to standard therapy. Can J Gastroenterol 2013; 27(5): 273–280

    PubMed Central  PubMed  Google Scholar 

  174. Grasland A, Sterpu R, Boussoukaya S, Mahe I. Autoimmune hepatitis induced by adalimumab with successful switch to abatacept. Eur J Clin Pharmacol 2012; 68(5): 895–898

    CAS  PubMed  Google Scholar 

  175. Weiler-Normann C, Sebode M, Lohse AW. Autoimmune hepatitis 2013 and beyond. Minerva Gastroenterol Dietol 2013; 59(2): 133–141

    CAS  PubMed  Google Scholar 

  176. Kurowski J, Melin-Aldana H, Bass L, Alonso EM, Ekong UD. Sirolimus as rescue therapy in pediatric autoimmune hepatitis. J Pediatr Gastroenterol Nutr 2014; 58(1): e4–e6

    PubMed  Google Scholar 

  177. Czaja AJ, Carpenter HA, Lindor KD. Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: a randomized placebo-controlled treatment trial. Hepatology 1999; 30(6): 1381–1386

    CAS  PubMed  Google Scholar 

  178. Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology 2000; 119(5): 1312–1316

    CAS  PubMed  Google Scholar 

  179. Sharzehi K, Huang MA, Schreibman IR, Brown KA. Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory or intolerant to conventional therapy. Can J Gastroenterol 2010; 24(10): 588–592

    PubMed Central  PubMed  Google Scholar 

  180. Hlivko JT, Shiffman ML, Stravitz RT, Luketic VA, Sanyal AJ, Fuchs M, Sterling RK. A single center review of the use of mycophenolate mofetil in the treatment of autoimmune hepatitis. Clin Gastroenterol Hepatol 2008; 6(9): 1036–1040

    CAS  PubMed  Google Scholar 

  181. Czaja AJ, Carpenter HA. Empiric therapy of autoimmune hepatitis with mycophenolate mofetil: comparison with conventional treatment for refractory disease. J Clin Gastroenterol 2005; 39(9): 819–825

    CAS  PubMed  Google Scholar 

  182. Chatur N, Ramji A, Bain VG, Ma MM, Marotta PJ, Ghent CN, Lilly LB, Heathcote EJ, Deschenes M, Lee SS, Steinbrecher UP, Yoshida EM. Transplant immunosuppressive agents in nontransplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with mycophenolate mofetil and tacrolimus. Liver Int 2005; 25(4): 723–727

    CAS  PubMed  Google Scholar 

  183. Inductivo-Yu I, Adams A, Gish RG, Wakil A, Bzowej NH, Frederick RT, Bonacini M. Mycophenolate mofetil in autoimmune hepatitis patients not responsive or intolerant to standard immunosuppressive therapy. Clin Gastroenterol Hepatol 2007; 5(7): 799–802

    CAS  PubMed  Google Scholar 

  184. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J Hepatol 1994; 21(6): 1040–1047

    CAS  PubMed  Google Scholar 

  185. Fernandes NF, Redeker AG, Vierling JM, Villamil FG, Fong TL. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am J Gastroenterol 1999; 94(1): 241–248

    CAS  PubMed  Google Scholar 

  186. Sciveres M, Caprai S, Palla G, Ughi C, Maggiore G. Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents. Aliment Pharmacol Ther 2004; 19(2): 209–217

    CAS  PubMed  Google Scholar 

  187. Malekzadeh R, Nasseri-Moghaddam S, Kaviani MJ, Taheri H, Kamalian N, Sotoudeh M. Cyclosporin A is a promising alternative to corticosteroids in autoimmune hepatitis. Dig Dis Sci 2001; 46(6): 1321–1327

    CAS  PubMed  Google Scholar 

  188. Czaja AJ. Emerging treatments for autoimmune hepatitis. Curr Drug Targets Inflamm Allergy 2002; 1(4): 317–326

    CAS  PubMed  Google Scholar 

  189. Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002; 35(1): 7–13

    CAS  PubMed  Google Scholar 

  190. Vierling JM, Flores PA. Evolving new therapies of autoimmune hepatitis. Clin Liver Dis 2002; 6: 825–50, ix

    PubMed  Google Scholar 

  191. Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des 2011; 17(29): 3120–3140

    CAS  PubMed  Google Scholar 

  192. Czaja AJ. Autoimmune hepatitis: focusing on treatments other than steroids. Can J Gastroenterol 2012; 26(9): 615–620

    PubMed Central  PubMed  Google Scholar 

  193. Van Thiel DH, Wright H, Carroll P, Abu-Elmagd K, Rodriguez-Rilo H, McMichael J, Irish W, Starzl TE. Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. Am J Gastroenterol 1995; 90(5): 771–776

    PubMed Central  PubMed  Google Scholar 

  194. Aqel BA, Machicao V, Rosser B, Satyanarayana R, Harnois DM, Dickson RC. Efficacy of tacrolimus in the treatment of steroid refractory autoimmune hepatitis. J Clin Gastroenterol 2004; 38(9): 805–809

    CAS  PubMed  Google Scholar 

  195. Tannous MM, Cheng J, Muniyappa K, Farooq I, Bharara A, Kappus M, Luketic V, Stravtiz RT, Fuchs M, Puri P, Sanyal A, Sterling R. Use of tacrolimus in the treatment of autoimmune hepatitis: a single centre experience. Aliment Pharmacol Ther 2011; 34(3): 405–407

    CAS  PubMed  Google Scholar 

  196. Kerkar N, Dugan C, Rumbo C, Morotti RA, Gondolesi G, Shneider BL, Emre S. Rapamycin successfully treats post-transplant autoimmune hepatitis. Am J Transplant 2005; 5(5): 1085–1089

    PubMed  Google Scholar 

  197. Casanovas T, Argudo A, Peña-Cala MC. Effectiveness and safety of everolimus in the treatment of autoimmune hepatitis related to anti-hepatitis C virus therapy after liver transplant: three case reports. Transplant Proc 2011; 43(6): 2233–2236

    CAS  PubMed  Google Scholar 

  198. Moreno-Otero R, García-Buey L, García-Sanchez A, Trapero-Marugán M. Autoimmune hepatitis after long-term methotrexate therapy for rheumatoid arthritis. Curr Drug Saf 2011; 6(3): 197–200

    CAS  PubMed  Google Scholar 

  199. Khokhar OS, Lewis JH. Hepatotoxicity of agents used in the management of inflammatory bowel disease. Dig Dis 2010; 28(3): 508–518

    PubMed  Google Scholar 

  200. Carey EJ, Somaratne K, Rakela J. Successful rituximab therapy in refractory autoimmune hepatitis and Evans syndrome. Rev Med Chil 2011; 139(11): 1484–1487

    PubMed  Google Scholar 

  201. Santos ES, Arosemena LR, Raez LE, O’Brien C, Regev A. Successful treatment of autoimmune hepatitis and idiopathic thrombocytopenic purpura with the monoclonal antibody, rituximab: case report and review of literature. Liver Int 2006; 26(5): 625–629

    CAS  PubMed  Google Scholar 

  202. Barth E, Clawson J. A case of autoimmune hepatitis treated with rituximab. Case Rep Gastroenterol 2010; 4(3): 502–509

    PubMed Central  PubMed  Google Scholar 

  203. Al-Busafi SA, Michel RP, Deschenes M. Rituximab for refractory autoimmune hepatitis: a case report. Arab J Gastroenterol 2013; 14(3): 135–138

    PubMed  Google Scholar 

  204. Weiler-Normann C, Schramm C, Quaas A, Wiegard C, Glaubke C, Pannicke N, Möller S, Lohse AW. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol 2013; 58(3): 529–534

    CAS  PubMed  Google Scholar 

  205. Fujii K, Rokutanda R, Osugi Y, Koyama Y, Ota T. Adult-onset Still’s disease complicated by autoimmune hepatitis: successful treatment with infliximab. Intern Med 2012; 51(9): 1125–1128

    CAS  PubMed  Google Scholar 

  206. Mancini S, Amorotti E, Vecchio S, Ponz de Leon M, Roncucci L. Infliximab-related hepatitis: discussion of a case and review of the literature. Intern Emerg Med 2010; 5(3): 193–200

    PubMed  Google Scholar 

  207. 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 Crohn’s Colitis 2012; 6(5): 630–631

    Google Scholar 

  208. 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(1): 75–79

    PubMed  Google Scholar 

  209. Efe C. Drug induced autoimmune hepatitis and TNF-α blocking agents: is there a real relationship? Autoimmun Rev 2013; 12(3): 337–339

    CAS  PubMed  Google Scholar 

  210. Schramm C, Bubenheim M, Adam R, Karam V, Buckels J, O’Grady JG, Jamieson N, Pollard S, Neuhaus P, Manns MM, Porte R, Castaing D, Paul A, Traynor O, Garden J, Friman S, Ericzon BG, Fischer L, Vitko S, Krawczyk M, Metselaar HJ, Foss A, Kilic M, Rolles K, Burra P, Rogiers X, Lohse AW. Primary liver transplantation for autoimmune hepatitis: a comparative analysis of the European Liver Transplant Registry. Liver Transpl 2010; 16(4): 461–469

    PubMed  Google Scholar 

  211. Czaja AJ. Diagnosis, pathogenesis, and treatment of autoimmune hepatitis after liver transplantation. Dig Dis Sci 2012; 57(9): 2248–2266

    CAS  PubMed  Google Scholar 

  212. Dbouk N, Parekh S. Impact of pretransplant antinuclear antibody and antismooth muscle antibody titers on disease recurrence and graft survival following liver transplantation in autoimmune hepatitis patients. J Gastroenterol Hepatol 2013; 28(3): 537–542

    PubMed Central  PubMed  Google Scholar 

  213. Manns MP, Bahr MJ. Recurrent autoimmune hepatitis after liver transplantation-when non-self becomes self. Hepatology 2000; 32(4 Pt 1): 868–870

    CAS  PubMed  Google Scholar 

  214. Czaja AJ. Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance. Liver Transpl 2002; 8(6): 505–513

    PubMed  Google Scholar 

  215. Rosen HR, Hinrichs DJ, Leistikow RL, Callender G, Wertheimer AM, Nishimura MI, Lewinsohn DM. Cutting edge: identification of hepatitis C virus-specific CD8+ T cells restricted by donor HLA alleles following liver transplantation. J Immunol 2004; 173(9): 5355–5359

    CAS  PubMed  Google Scholar 

  216. Ratziu V, Samuel D, Sebagh M, Farges O, Saliba F, Ichai P, Farahmand H, Gigou M, Féray C, Reynès M, Bismuth H. Longterm follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease. J Hepatol 1999; 30(1): 131–141

    CAS  PubMed  Google Scholar 

  217. Schreuder TC, Hübscher SG, Neuberger J. Autoimmune liver diseases and recurrence after orthotopic liver transplantation: what have we learned so far? Transpl Int 2009; 22(2): 144–152

    PubMed  Google Scholar 

  218. Duclos-Vallée JC, Sebagh M, Rifai K, Johanet C, Ballot E, Guettier C, Karam V, Hurtova M, Feray C, Reynes M, Bismuth H, Samuel D. A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence. Gut 2003; 52(6): 893–897

    PubMed Central  PubMed  Google Scholar 

  219. Ayata G, Gordon FD, Lewis WD, Pomfret E, Pomposelli JJ, Jenkins RL, Khettry U. Liver transplantation for autoimmune hepatitis: a long-term pathologic study. Hepatology 2000; 32(2): 185–192

    CAS  PubMed  Google Scholar 

  220. Gautam M, Cheruvattath R, Balan V. Recurrence of autoimmune liver disease after liver transplantation: a systematic review. Liver Transpl 2006; 12(12): 1813–1824

    PubMed  Google Scholar 

  221. Milkiewicz P, Hubscher SG, Skiba G, Hathaway M, Elias E. Recurrence of autoimmune hepatitis after liver transplantation. Transplantation 1999; 68(2): 253–256

    CAS  PubMed  Google Scholar 

  222. Hurtova M, Duclos-Vallée JC, Johanet C, Emile JF, Roque-Afonso AM, Feray C, Bismuth H, Samuel D. Successful tacrolimus therapy for a severe recurrence of type 1 autoimmune hepatitis in a liver graft recipient. Liver Transpl 2001; 7(6): 556–558

    CAS  PubMed  Google Scholar 

  223. González-Koch A, Czaja AJ, Carpenter HA, Roberts SK, Charlton MR, Porayko MK, Rosen CB, Wiesner RH. Recurrent autoimmune hepatitis after orthotopic liver transplantation. Liver Transpl 2001; 7(4): 302–310

    PubMed  Google Scholar 

  224. 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): 459–465

    PubMed  Google Scholar 

  225. Ilyas JA, O’Mahony CA, Vierling JM. Liver transplantation in autoimmune liver diseases. Best Pract Res Clin Gastroenterol 2011; 25(6): 765–782

    PubMed  Google Scholar 

  226. Guido M, Burra P. De novo autoimmune hepatitis after liver transplantation. Semin Liver Dis 2011; 31(1): 71–81

    PubMed  Google Scholar 

  227. Kerkar N, Hadzić N, Davies ET, Portmann B, Donaldson PT, Rela M, Heaton ND, Vergani D, Mieli-Vergani G. De-novo autoimmune hepatitis after liver transplantation. Lancet 1998; 351(9100): 409–413

    CAS  PubMed  Google Scholar 

  228. Heneghan MA, Portmann BC, Norris SM, Williams R, Muiesan P, Rela M, Heaton ND, O’Grady JG. Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults. Hepatology 2001; 34(3): 464–470

    CAS  PubMed  Google Scholar 

  229. Verdonk RC, Dijkstra G, Haagsma EB, Shostrom VK, Van den Berg AP, Kleibeuker JH, Langnas AN, Sudan DL. Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease. Am J Transplant 2006; 6(6): 1422–1429

    CAS  PubMed  Google Scholar 

  230. Hampton DD, Poleski MH, Onken JE. Inflammatory bowel disease following solid organ transplantation. Clin Immunol 2008; 128(3): 287–293

    CAS  PubMed  Google Scholar 

  231. Ferri S, Longhi MS, De Molo C, Lalanne C, Muratori P, Granito A, Hussain MJ, Ma Y, Lenzi M, Mieli-Vergani G, Bianchi FB, Vergani D, Muratori L. A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis. Hepatology 2010; 52(3): 999–1007

    CAS  PubMed  Google Scholar 

  232. Longhi MS, Hussain M, Mieli-Vergani G, Kwok W, Ma Y, Vergani D. Auto-antigen-specific regulatory T-cells, a potential tool for immune-tolerance reconstitution in type-2 autoimmune hepatitis. Hepatology 2011; 53: 001–002

    Google Scholar 

  233. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 2010; 10(7): 490–500

    CAS  PubMed  Google Scholar 

  234. Schulze-Koops H, Skapenko A. Inflammation: TREG cell control of autoimmune inflammation: a matter of timing? Nat Rev Rheumatol 2010; 6(11): 620–621

    PubMed  Google Scholar 

  235. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 2010; 11(1): 7–13

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Surgery, Baylor College of Medicine, Baylor-St. Luke’s Medical Center, Houston, TX, 77030, USA

    Farhad Sahebjam & John M. Vierling

Authors
  1. Farhad Sahebjam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John M. Vierling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John M. Vierling.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahebjam, F., Vierling, J.M. Autoimmune hepatitis. Front. Med. 9, 187–219 (2015). https://doi.org/10.1007/s11684-015-0386-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-015-0386-y

Keywords

Search

Navigation