Treatment of autoimmune hepatitis: A review of current and evolving therapies

Journal of Gastroenterology and Hepatology (Australia)

Volumn 26, Issue 4, 2011, Pages 619-627

  Jothimani, Dinesh ^a   Cramp, Matthew E ^a   Mitchell, Jonathon D ^a   Cross, Tim J S ^a  

^a DERRIFORD HOSPITAL   (United Kingdom)

Author keywords

Autoimmune hepatitis; Azathioprine; Corticosteroid; Diagnosis; Immunosuppression

Indexed keywords

ASPARTATE AMINOTRANSFERASE; AZATHIOPRINE; BUDESONIDE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; CYCLOSPORIN; CYCLOSPORIN A; IMMUNOGLOBULIN G4; INFLIXIMAB; MERCAPTOPURINE; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PENICILLAMINE; PREDNISOLONE; RAPAMYCIN; RITUXIMAB; TACROLIMUS; TIOGUANINE; URSODEOXYCHOLIC ACID;

ABDOMINAL PAIN; ACNE; ACUTE PANCREATITIS; ALOPECIA; AUTOIMMUNE HEPATITIS; BILE DUCT DISEASE; BODY FAT DISTRIBUTION; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; CATARACT; COMBINATION CHEMOTHERAPY; CYTOMEGALOVIRUS INFECTION; CYTOPENIA; DIABETES MELLITUS; DIARRHEA; DISEASE COURSE; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG MECHANISM; DRUG MEGADOSE; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ECHOGRAPHY; ENTERITIS; ESOPHAGITIS; FLU LIKE SYNDROME; FULMINANT HEPATIC FAILURE; GASTRITIS; GENOTYPE; GINGIVA HYPERTROPHY; HAIR LOSS; HIRSUTISM; HISTOPATHOLOGY; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; IMMUNOSUPPRESSIVE TREATMENT; LIVER FUNCTION TEST; LIVER TOXICITY; LIVER TRANSPLANTATION; LOW DRUG DOSE; MENTAL DISEASE; MONOTHERAPY; MOON FACE; MUSCLE ATROPHY; NAUSEA; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; OPPORTUNISTIC INFECTION; ORGAN TRANSPLANTATION; OSTEOPOROSIS; PANCREATITIS; PANCYTOPENIA; PRIORITY JOURNAL; PSORIASIS; REMISSION; REVIEW; RHEUMATOID ARTHRITIS; SEIZURE; SENSITIVITY AND SPECIFICITY; SIDE EFFECT; TREATMENT RESPONSE; TREMOR; VOMITING; WEIGHT GAIN;

EID: 79952853189     PISSN: 08159319     EISSN: 14401746     Source Type: Journal    
DOI: 10.1111/j.1440-1746.2010.06579.x     Document Type: Review

References (95)

1. Ngu JH, Bechly K, Chapman BA etal. Population-based epidemiology study autoimmune hepatitis-a disease of older women? J. Gastroenterol. Hepatol. 2010;25: 1681-6.
2. 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: 713-7.
3. Nakamura K, Yoneda M, Yokohama S etal. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J. Gastroenterol. Hepatol. 1998; 13: 490-5.
4. Newton JL, Burt AD, Park JB, Mathew J, Bassendine MF, James OF. Autoimmune hepatitis in older patients. Age Ageing. 1997; 26: 441-4.
5. Donaldson PT, Doherty DG, Hayllar KM, McFarlane IG, Johnson PJ, Williams R. Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology. 1991; 13: 701-6.
6. Miyake Y, Iwasaki Y, Takaki A etal. Human leukocyte antigen DR status and clinical features in Japanese patients with type 1 autoimmune hepatitis. Hepatol. Res. 2008; 38: 96-102.
7. Manns MP, Vogel A. Autoimmune hepatitis, from mechanisms to therapy. Hepatology. 2006; 43: S132-44.
8. Schlaak JF, Lohr H, Gallati H, Meyer zum Buschenfelde KH, Fleischer B. Analysis of the in vitro cytokine production by liver-infiltrating T cells of patients with autoimmune hepatitis. Clin. Exp. Immunol. 1993; 94: 168-73.
9. Derkow K, Loddenkemper C, Mintern J etal. Differential priming of CD8 and CD4 T-cells in animal models of autoimmune hepatitis and cholangitis. Hepatology. 2007; 46: 1155-65.
10. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J. Autoimmun. 2010; 34: 7-14.
11. Silveira MG, Lindor KD. Overlap syndromes with autoimmune hepatitis in chronic cholestatic liver diseases. Expert Rev. Gastroenterol. Hepatol. 2007; 1: 329-40.
12. Baeres M, Herkel J, Czaja AJ etal. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut. 2002; 51: 259-64.
13. Manns M, Gerken G, Kyriatsoulis A, Staritz M, Meyer zum Buschenfelde KH. Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet. 1987; 1: 292-4.
14. Czaja A, Manns M. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology. 2010; 139: 58-72.
15. Miyake Y, Iwasaki Y, Kobashi H etal. Autoimmune hepatitis with acute presentation in Japan. Dig. Liver Dis. 2010; 42: 51-4.
16. Alvarez F, Berg PA, Bianchi FB etal. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J. Hepatol. 1999; 31: 929-38.
17. Toda G, Zeniya M, Watanabe F etal. Present status of autoimmune hepatitis in Japan-correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis. J. Hepatol. 1997; 26: 1207-12.
18. Hennes EM, Zeniya M, Czaja AJ etal. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008; 48: 169-76.
19. Czaja AJ. Performance parameters of the diagnostic scoring systems for autoimmune hepatitis. Hepatology. 2008; 48: 1540-8.
20. Miyake Y, Iwasaki Y, Kobashi H etal. Clinical features of autoimmune hepatitis diagnosed based on simplified criteria of the International Autoimmune Hepatitis Group. Dig. Liver Dis. 2010; 42: 210-5.
21. Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002; 36: 479-97.
22. Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology. 2002; 35: 7-13.
23. Montano Loza AJ, Czaja AJ. Current therapy for autoimmune hepatitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 2007; 4: 202-14.
24. Feld JJ, Dinh H, Arenovich T, Marcus VA, Wanless IR, Heathcote EJ. Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology. 2005; 42: 53-62.
25. Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q. J. Med. 1971; 40: 159-85.
26. Manns MP, Czaja AJ, Gorham JD etal. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010; 51: 2193-213.
27. Murray-Lyon IM, Stern RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet. 1973; 1: 735-7.
28. Last PM. The treatment of active chronic infectious hepatitis with ACTH (corticotrophin) and cortisone. Med. J. Aust. 1957; 44: 672-6.
29. Czaja AJ, Carpenter HA. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J. Hepatol. 2004; 40: 646-52.
30. Bluth MH, Kohlhoff S, Norowitz KB etal. Immune responses in autoimmune hepatitis: effect of prednisone and azathioprine treatment: case report. Int. J. Med. Sci. 2009; 6: 177-83.
31. Cotler SJ, Jakate S, Jensen DM. Resolution of cirrhosis in autoimmune hepatitis with corticosteroid therapy. J. Clin. Gastroenterol. 2001; 32: 428-30.
32. Montano-Loza AJ, Carpenter HA, Czaja AJ. Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse. Am. J. Gastroenterol. 2007; 102: 1005-12.
33. Coverdale SA, Field J, Farrell GC. How reversible is hepatic functional impairment in autoimmune hepatitis? J. Gastroenterol. Hepatol. 2003; 18: 371-5.
34. Czaja AJ, Carpenter HA. Empiric therapy of autoimmune hepatitis with mycophenolate mofetil: comparison with conventional treatment for refractory disease. J. Clin. Gastroenterol. 2005; 39: 819-25.
35. Hoes JN, Jacobs JW, Verstappen SM, Bijlsma JW, Van der Heijden GJ. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann. Rheum. Dis. 2009; 68: 1833-8.
36. Elion GB. The George Hitchings and Gertrude Elion Lecture. The pharmacology of azathioprine. Ann. N. Y. Acad. Sci. 1993; 685: 400-7.
37. Banerjee S, Rahhal R, Bishop WP. Azathioprine monotherapy for maintenance of remission in pediatric patients with autoimmune hepatitis. J. Pediatr. Gastroenterol. Nutr. 2006; 43: 353-6.
38. Stellon AJ, Hegarty JE, Portmann B, Williams R. Randomized controlled trial of azathioprine withdrawal in autoimmune chronic active hepatitis. Lancet. 1985; 1: 668-70.
39. Hindorf U, Jahed K, Bergquist A etal. Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis. J. Hepatol. 2010; 52: 106-11.
40. 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: 584-91.
41. Miyake Y, Yamamoto K. Current status of autoimmune hepatitis in Japan. Acta Med. Okayama. 2008; 62: 217-26.
42. Montano-Loza AJ, Carpenter HA, Czaja AJ. Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease. Hepatology. 2007; 46: 1138-45.
43. Hino T, Kumashiro R, Ide T etal. Predictive factors for remission and death in 73 patients with autoimmune hepatitis in Japan. Int. J. Mol. Med. 2003; 11: 749-55.
44. Hegarty JE, Nouri Aria KT, Portmann B, Eddleston AL, Williams R. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology. 1983; 3: 685-9.
45. Verma S, Gunuwan B, Mendler M, Govindrajan S, Redeker A. Factors predicting relapse and poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy. Am. J. Gastroenterol. 2004; 99: 1510-6.
46. Golshayan D, Pascual M, Vogt B. Mycophenolic acid formulations in adult renal transplantation-update on efficacy and tolerability. Ther. Clin. Risk Manag. 2009; 5: 341-51.
47. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000; 47: 85-118.
48. Schuppan D, Schneider HT, Hahn EG. Successful treatment of therapy-refractory autoimmune hepatitis with mycophenolate mofetil. Hepatology. 1998; 28: A1960.
49. Richardson PD, James PD, Ryder SD. Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J. Hepatol. 2000; 33: 371-5.
50. Devlin SM, Swain MG, Urbanski SJ, Burak KW. Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory to standard therapy. Can. J. Gastroenterol. 2004; 18: 321-6.
51. Brunt EM, Di Bisceglie AM. Histological changes after the use of mycophenolate mofetil in autoimmune hepatitis. Hum. Pathol. 2004; 35: 509-12.
52. Chatur N, Ramji A, Bain VG etal. Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with mycophenolate mofetil and tacrolimus. Liver Int. 2005; 25: 723-7.
53. Inductivo-Yu I, Adams A, Gish RG etal. Mycophenolate mofetil in autoimmune hepatitis patients not responsive or intolerant to standard immunosuppressive therapy. Clin. Gastroenterol. Hepatol. 2007; 5: 799-802.
54. Hlivko JT, Shiffman ML, Stravitz RT etal. A single center review of the use of mycophenolate mofetil in the treatment of autoimmune hepatitis. Clin. Gastroenterol. Hepatol. 2008; 6: 1036-40.
55. Hennes EM, Oo YH, Schramm C etal. Mycophenolate mofetil as second line therapy in autoimmune hepatitis? Am. J. Gastroenterol. 2008; 103: 3063-70.
56. Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig. Dis. Sci. 2009; 54: 2519-22.
57. Hamedani R, Feldman RD, Feagan BG. Review article: Drug development in inflammatory bowel disease: budesonide-a model of targeted therapy. Aliment. Pharmacol. Ther. 1997; 11 (Suppl. 3): 98-107. discussion -8.
58. Danielsson A, Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment. Pharmacol. Ther. 1994; 8: 585-90.
59. Zandieh I, Krygier D, Wong V etal. The use of budesonide in the treatment of autoimmune hepatitis in Canada. Can. J. Gastroenterol. 2008; 22: 388-92.
60. Csepregi A, Rocken C, Treiber G, Malfertheiner P. Budesonide induces complete remission in autoimmune hepatitis. World J. Gastroenterol. 2006; 12: 1362-6.
61. Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology. 2000; 119: 1312-6.
62. Manns MP, Woynarowski M, Kreisel W etal. Azathioprine with budesonide induces remission more effectively than with prednisone in patients with autoimmune hepatitis. Gastroenterology. 2010; 139: 1198-206.
63. 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: 1381-6.
64. Miyake Y, Iwasaki Y, Kobashi H etal. Efficacy of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis. Dig. Liver Dis. 2010; 42: 210-5.
65. Beuers U, Rust C. Overlap syndromes. Semin. Liver Dis. 2005; 25: 311-20.
66. 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: 1321-7.
67. Fernandes NF, Redeker AG, Vierling JM, Villamil FG, Fong TL. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am. J. Gastroenterol. 1999; 94: 241-8.
68. Alvarez F, Ciocca M, Canero-Velasco C etal. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J. Hepatol. 1999; 30: 222-7.
69. Fagiuoli S, Bruni F, Bravi M etal. Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver diseases. Dig. Liver Dis. 2007; 39 (Suppl. 3): S379-85.
70. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J. Hepatol. 1994; 21: 1040-7.
71. Larsen FS, Vainer B, Eefsen M, Bjerring PN, Adel Hansen B. Low-dose tacrolimus ameliorates liver inflammation and fibrosis in steroid refractory autoimmune hepatitis. World J. Gastroenterol. 2007; 13: 3232-6.
72. 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: 805-9.
73. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology. 1996; 110: 271-4.
74. de Boer NK, van Nieuwkerk CM, Aparicio Pages MN, de Boer SY, Derijks LJ, Mulder CJ. Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine. Eur. J. Gastroenterol. Hepatol. 2005; 17: 457-61.
75. de Jong DJ, Derijks LJ, Naber AH, Hooymans PM, Mulder CJ. Safety of thiopurines in the treatment of inflammatory bowel disease. Scand. J. Gastroenterol. Suppl. 2003; 69-72.
76. Santos ESAL, 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: 625-9.
77. Evans JT, Oates JC, Self SE, Reuben A. Rituximab-responsive cryoglobulinemic glomerulonephritis in a patient with autoimmune hepatitis. J. Clin. Gastroenterol. 2008; 42: 862-3.
78. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003; 22: 7359-68.
79. Burak K, Williamson-Coffey S, Swain M etal. Rituximab for refractory autoimmune hepatitis: interim results of a phase 1 study. Canadian Digestive Disease Week. 2009.
80. Kerkar N, Dugan C, Rumbo C etal. Rapamycin successfully treats post-transplant autoimmune hepatitis. Am. J. Transplant. 2005; 5: 1085-9.
81. Burak KW, Urbanski SJ, Swain MG. Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate. J. Hepatol. 1998; 29: 990-3.
82. Kanzler S, Gerken G, Dienes HP, Meyer zum Buschenfelde KH, Lohse AW. Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis-report of three cases. Z Gastroenterol. 1997; 35: 571-8.
83. Weiler-Normann C, Wiegard C, Schramm C, Lohse AW. A case of difficult-to-treat autoimmune hepatitis successfully managed by TNF-alpha blockade. Am. J. Gastroenterol. 2009; 104: 2877-8.
84. Ghazale A, Chari ST, Zhang L etal. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008; 134: 706-15.
85. Alderlieste YA, van den Elzen BD, Rauws EA, Beuers U. Immunoglobulin G4-associated cholangitis: one variant of immunoglobulin G4-related systemic disease. Digestion. 2009; 79: 220-8.
86. Toruner M, Loftus EV, Jr., Harmsen WS etal. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008; 134: 929-36.
87. Seksik P, Cosnes J, Sokol H, Nion-Larmurier I, Gendre JP, Beaugerie L. Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine. Aliment. Pharmacol. Ther. 2009; 29: 1106-13.
88. Vijayan VK. Parasitic lung infections. Curr. Opin. Pulm. Med. 2009; 15: 274-82.
89. O'Neill BP, Vernino S, Dogan A, Giannini C. EBV-associated lymphoproliferative disorder of CNS associated with the use of mycophenolate mofetil. Neuro-Oncol. 2007; 9: 364-9.
90. Vernino S, Salomao DR, Habermann TM, O'Neill BP. Primary CNS lymphoma complicating treatment of myasthenia gravis with mycophenolate mofetil. Neurology. 2005; 65: 639-41.
91. Pourfarziani V, Taheri S, Lessan-Pezeshki M etal. Lymphoma after living donor kidney transplantation: an Iranian multicenter experience. Int. Urol. Nephrol. 2008; 40: 1089-94.
92. Bichari W, Bartiromo M, Mohey H etal. Significant risk factors for occurrence of cancer after renal transplantation: a single center cohort study of 1265 cases. Transplant. Proc. 2009; 41: 672-3.
93. Hofbauer GF, Anliker M, Arnold A etal. Swiss clinical practice guidelines for skin cancer in organ transplant recipients. Swiss Med. Wkly. 2009; 139: 407-15.
94. Teufel A, Weinmann A, Centner C etal. Hepatocellular carcinoma in patients with autoimmune hepatitis. World J. Gastroenterol. 2009; 15: 578-82.
95. Michitaka K, Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M. Etiology of liver cirrhosis in Japan: a nationwide survey. J. Gastroenterol. 2010; 45: 86-94.