Advances in the current treatment of autoimmune hepatitis

Digestive Diseases and Sciences

Volumn 57, Issue 8, 2012, Pages 1996-2010

  Czaja, Albert J ^a  

^a MAYO CLINIC   (United States)

Author keywords

Advances; Autoimmune hepatitis; Nonstandard medications; Treatment

Indexed keywords

AZATHIOPRINE; BUDESONIDE; CYCLOSPORIN; CYCLOSPORIN A; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PREDNISONE; TACROLIMUS;

AUTOIMMUNE HEPATITIS; CONGENITAL MALFORMATION; CUSHINGOID SYNDROME; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG INDICATION; DRUG MECHANISM; DRUG SAFETY; HUMAN; LEUKOPENIA; LYMPHOPROLIFERATIVE DISEASE; MAINTENANCE THERAPY; MATHEMATICAL MODEL; NAUSEA; PARESTHESIA; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; RELAPSE; REVIEW; TREATMENT DURATION; TREATMENT OUTCOME;

GASTROENTEROLOGY; HEPATITIS, AUTOIMMUNE; HUMANS; RECURRENCE;

EID: 84866391821     PISSN: 01632116     EISSN: 15732568     Source Type: Journal    
DOI: 10.1007/s10620-012-2151-2     Document Type: Review

References (197)

1. Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med. 1971;40:159-185.
2. Soloway RD, Summerskill WH, Baggenstoss AH, et al. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology. 1972;63:820-833.
3. Murray-Lyon IM, Stern RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet. 1973;1:735-737.
4. Czaja AJ, Carpenter HA. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol. 2004;40: 646-652.
5. Mohamadnejad M, Malekzadeh R, Nasseri-Moghaddam S, et al. Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis. Dig Dis Sci. 2005;50:547-551.
6. Roberts SK, Therneau TM, Czaja AJ. Prognosis of histological cirrhosis in type 1 autoimmune hepatitis. Gastroenterology. 1996;110:848-857.
7. Floreani A, Niro G. Rosa Rizzotto E, et al. Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study. Aliment Pharmacol Ther. 2006;24:1051-1057.
8. Seo S, Toutounjian R, Conrad A, Blatt L, Tong MJ. Favorable outcomes of autoimmune hepatitis in a community clinic setting. J Gastroenterol Hepatol. 2008;23:1410-1414.
9. Manns MP, Czaja AJ, Gorham JD, et al. Practice guidelines of the American association for the study of liver diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193-2213.
10. Czaja AJ, Bianchi FB, Carpenter HA, et al. Treatment challenges and investigational opportunities in autoimmune hepatitis. Hepatology. 2005;41:207-215.
11. 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;46:1138-1145.
12. Czaja AJ, Davis GL, Ludwig J, Taswell HF. Complete resolution of inflammatory activity following corticosteroid treatment of HBsAg-negative chronic active hepatitis. Hepatology. 1984; 4:622-627.
13. Czaja AJ. Safety issues in the management of autoimmune hepatitis. Expert Opin Drug Saf. 2008;7:319-333.
14. Czaja AJ, Ammon HV, Summerskill WH. Clinical features and prognosis of severe chronic active liver disease (CALD) after corticosteroid-induced remission. Gastroenterology. 1980;78: 518-523.
15. Hegarty JE, Nouri Aria KT, Portmann B, Eddleston AL, Williams R. Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis. Hepatology. 1983; 3:685-689.
16. Czaja AJ, Menon KV, Carpenter HA. Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis: a retrospective analysis. Hepatology. 2002;35:890-897.
17. Czaja AJ. Current and future treatments of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol. 2009;3:269-291.
18. Czaja AJ. Emerging opportunities for site-specific molecular and cellular interventions in autoimmune hepatitis. Dig Dis Sci. 2010;55:2712-2726.
19. Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Design. 2011; 17:3120-3140.
20. Alvarez F, Berg PA, Bianchi FB, et al. International autoimmune hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929-938.
21. Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology. 2010;139:58-72.
22. Hyams JS, Ballow M, Leichtner AM. Cyclosporine treatment of autoimmune chronic active hepatitis. Gastroenterology. 1987; 93:890-893.
23. Person JL, McHutchison JG, Fong TL, Redeker AG. A case of cyclosporine-sensitive, steroid-resistant, autoimmune chronic active hepatitis. J Clin Gastroenterol. 1993;17:317-320.
24. Van Thiel DH, Wright H, Carroll P, et al. Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. Am J Gastroenterol. 1995;90:771-776.
25. Jackson LD, Song E. Cyclosporin in the treatment of corticosteroid resistant autoimmune chronic active hepatitis. Gut. 1995;36:459-461.
26. Debray D, Maggiore G, Girardet JP, Mallet E, Bernard O. Efficacy of cyclosporin A in children with type 2 autoimmune hepatitis. J Pediatr. 1999;135:111-114.
27. Fernandes NF, Redeker AG, Vierling JM, Villamil FG, Fong TL. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am J Gastroenterol. 1999;94:241-248.
28. Malekzadeh R, Nasseri-Moghaddam S, Kaviani MJ, et al. Cyclosporin A is a promising alternative to corticosteroids in autoimmune hepatitis. Dig Dis Sci. 2001;46:1321-1327.
29. Hurtova M, Duclos-Vallee JC, Johanet C, et al. Successful tacrolimus therapy for a severe recurrence of type 1 autoimmune hepatitis in a liver graft recipient. Liver Transpl. 2001;7: 556-558.
30. Aqel BA, Machicao V, Rosser B, et al. Efficacy of tacrolimus in the treatment of steroid refractory autoimmune hepatitis. J Clin Gastroenterol. 2004;38:805-809.
31. 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;13:3232-3236.
32. Tannous MM, Cheng J, Muniyappa K, et al. Use of tacrolimus in the treatment of autoimmune hepatitis: a single centre experience. Aliment Pharmacol Ther. 2011;34:405-407.
33. Danielsson A, Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther. 1994;8:585-590.
34. Wiegand J, Schuler A, Kanzler S, et al. Budesonide in previously untreated autoimmune hepatitis. Liver Int. 2005;25:927-934.
35. Csepregi A, Rocken C, Treiber G, Malfertheiner P. Budesonide induces complete remission in autoimmune hepatitis. World J Gastroenterol. 2006;12:1362-1366.
36. Zandieh I, Krygier D, Wong V, et al. The use of budesonide in the treatment of autoimmune hepatitis in Canada. Can J Gastroenterol. 2008;22:388-392.
37. Manns MP, Woynarowski M, Kreisel W, et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010;139:1198-1206.
38. Snider KR, Potter TG. Budesonide for the treatment of autoimmune hepatitis. Ann Pharmacother. 2011;45:1144-1150.
39. 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;33:371-375.
40. 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: 321-326.
41. Czaja AJ, Carpenter HA. Empiric therapy of autoimmune hepatitis with mycophenolate mofetil: comparison with conventional treatment for refractory disease. J Clin Gastroenterol. 2005;39:819-825.
42. Inductivo-Yu I, Adams A, Gish RG, et al. Mycophenolate mofetil in autoimmune hepatitis patients not responsive or intolerant to standard immunosuppressive therapy. Clin Gastroen terol Hepatol. 2007;5:799-802.
43. Hennes EM, Oo YH, Schramm C, et al. Mycophenolate mofetil as second line therapy in autoimmune hepatitis? Am J Gastroenterol. 2008;103:3063-3070.
44. Hlivko JT, Shiffman ML, Stravitz RT, et al. A single center review of the use of mycophenolate mofetil in the treatment of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2008;6: 1036-1040.
45. Aw MM, Dhawan A, Samyn M, Bargiota A, Mieli-Vergani G. Mycophenolate mofetil as rescue treatment for autoimmune liver disease in children: a 5-year follow-up. J Hepatol. 2009; 51:156-160.
46. Wolf DC, Bojito L, Facciuto M, Lebovics E. Mycophenolate mofetil for autoimmune hepatitis: a single practice experience. Dig Dis Sci. 2009;54:2519-2522.
47. 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;24:588-592.
48. Zachou K, Gatselis N, Papadamou G, Rigopoulou EI, Dalekos GN. Mycophenolate for the treatment of autoimmune hepatitis: prospective assessment of its efficacy and safety for induction and maintenance of remission in a large cohort of treatmentnaive patients. J Hepatol. 2011;55:636-646.
49. Baven-Pronk AM, Coenraad MJ, van Buuren HR, et al. The role of mycophenolate mofetil in the management of autoimmune hepatitis and overlap syndromes. Aliment Pharmacol Ther. 2011;34:335-343.
50. Fallatah HI, Akbar HO. Mycophenolate mofetil as a rescue therapy for autoimmune hepatitis patients who are not responsive to standard therapy. Expert Rev Gastroenterol Hepatol. 2011;5:517-522.
51. Czaja AJ, Beaver SJ, Shiels MT. Sustained remission after corticosteroid therapy of severe hepatitis B surface antigennegative chronic active hepatitis. Gastroenterology. 1987;92: 215-219.
52. 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: 1005-1012.
53. Kanzler S, Lohr H, Gerken G, Galle PR, Lohse AW. Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience. Z Gastroenterol. 2001;39:339-341, 344-338.
54. Kanzler S, Gerken G, Lohr H, et al. Duration of immunosuppressive therapy in autoimmune hepatitis. J Hepatol. 2001;34: 354-355.
55. Czaja AJ, Wolf AM, Baggenstoss AH. Laboratory assessment of severe chronic active liver disease during and after corticosteroid therapy: correlation of serum transaminase and gamma globulin levels with histologic features. Gastroenterology. 1981; 80:687-692.
56. Luth S, Herkel J, Kanzler S, et al. Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis. J Clin Gastroenterol. 2008;42:926-930.
57. Czaja AJ, Ludwig J, Baggenstoss AH, Wolf A. Corticosteroidtreated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis. N Engl J Med. 1981;304: 5-9.
58. Czaja AJ. Late relapse of type 1 autoimmune hepatitis after corticosteroid withdrawal. Dig Dis Sci. 2010;55:1761-1769.
59. 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;99:1510-1516.
60. Davis GL, Czaja AJ, Ludwig J. Development and prognosis of histologic cirrhosis in corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis. Gastroenterology. 1984;87:1222-1227.
61. Schalm SW, Korman MG, Summerskill WH, Czaja AJ, Baggenstoss AH. Severe chronic active liver disease. Prognostic significance of initial morphologic patterns. Am J Dig Dis. 1977;22:973-980.
62. Baggenstoss AH, Soloway RD, Summerskill WH, Elveback LR, Schoenfield LJ. Chronic active liver disease. The range of histologic lesions, their response to treatment, and evolution. Hum Pathol. 1972;3:183-198.
63. Czaja AJ, Carpenter HA. Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis. Liver Int. 2003;23:116-123.
64. Soloway RD, Baggenstoss AH, Schoenfield LJ, Summerskill WH. Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy. Am J Dig Dis. 1971;16:1082-1086.
65. Theodossi A, Skene AM, Portmann B, et al. Observer variation in assessment of liver biopsies including analysis by kappa statistics. Gastroenterology. 1980;79:232-241.
66. Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36:479-497.
67. 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;52:1857; author reply 1857-1858.
68. Miyake Y, Iwasaki Y, Terada R, et al. Persistent normalization of serum alanine aminotransferase levels improves the prognosis of type 1 autoimmune hepatitis. J Hepatol. 2005;43:951-957.
69. Vergani D, Choudhuri K, Bogdanos DP, Mieli-Vergani G. Pathogenesis of autoimmune hepatitis. Clin Liver Dis. 2002;6: 727-737.
70. Czaja AJ. Autoimmune hepatitis. Part A: Pathogenesis. Expert Rev Gastroenterol Hepatol. 2007;1:113-128.
71. Montano-Loza AJ, Carpenter HA, Czaja AJ. Consequences of treatment withdrawal in type 1 autoimmune hepatitis. Liver Int. 2007;27:507-515.
72. Stellon AJ, Keating JJ, Johnson PJ, McFarlane IG, Williams R. Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal. Hepatology. 1988;8:781-784.
73. Johnson PJ, McFarlane IG, Williams R. Azathioprine for longterm maintenance of remission in autoimmune hepatitis. N Engl J Med. 1995;333:958-963.
74. Czaja AJ. Low-dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis. Hepatology. 1990;11:1044-1049.
75. Seela S, Sheela H, Boyer JL. Autoimmune hepatitis type 1: safety and efficacy of prolonged medical therapy. Liver Int. 2005;25:734-739.
76. Schalm SW, Ammon HV, Summerskill WH. Failure of customary treatment in chronic active liver disease: causes and management. Ann Clin Res. 1976;8:221-227.
77. Czaja AJ, Davis GL, Ludwig J, Baggenstoss AH, Taswell HF. Autoimmune features as determinants of prognosis in steroidtreated chronic active hepatitis of uncertain etiology. Gastroenterology. 1983;85:713-717.
78. Yeoman AD, Westbrook RH, Zen Y, et al. Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis. Hepatology. 2011;53:926-934.
79. Sanchez-Urdazpal L, Czaja AJ, van Hoek B, Krom RA, Wiesner RH. Prognostic features and role of liver transplantation in severe corticosteroid-treated autoimmune chronic active hepatitis. Hepatology. 1992;15:215-221.
80. Czaja AJ, Rakela J, Ludwig J. Features reflective of early prognosis in corticosteroid-treated severe autoimmune chronic active hepatitis. Gastroenterology. 1988;95:448-453.
81. Czaja AJ. Autoantibodies as prognostic markers in autoimmune liver disease. Dig Dis Sci. 2010;55:2144-2161.
82. Czaja AJ. Rapidity of treatment response and outcome in type 1 autoimmune hepatitis. J Hepatol. 2009;51:161-167.
83. Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology. 1993;105:1502-1507.
84. Czaja AJ, Strettell MD, Thomson LJ, et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology. 1997;25:317-323.
85. Czaja AJ, Carpenter HA. Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. Hepatology. 2006;43:532-538.
86. De Paoli P, Battistin S, Santini GF. Age-related changes in human lymphocyte subsets: progressive reduction of the CD4 CD45R (suppressor inducer) population. Clin Immunol Immunopathol. 1988;48:290-296.
87. Murasko DM, Goonewardene IM. T-cell function in aging: mechanisms of decline. Annu Rev Gerontol Geriatr. 1990;10: 71-96.
88. Talor E, Rose NR. Hypothesis: the aging paradox and autoimmune disease. Autoimmunity. 1991;8:245-249.
89. Schwab R, Russo C, Weksler ME. Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans. Eur J Immunol. 1992;22:2989-2993.
90. Rowley MJ, Buchanan H, Mackay IR. Reciprocal change with age in antibody to extrinsic and intrinsic antigens. Lancet. 1968;2:24-26.
91. Czaja AJ. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2008;6:379-388.
92. 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;1:292-294.
93. Stechemesser E, Klein R, Berg PA. Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology. 1993;18:1-9.
94. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet. 2000;355:1510-1515.
95. Volkmann M, Luithle D, Zentgraf H, et al. SLA/LP/tRNP((Ser)Sec) antigen in autoimmune hepatitis: identification of the native protein in human hepatic cell extract. J Autoimmun. 2010;34:59-65.
96. Volkmann M, Martin L, Baurle A, et al. Soluble liver antigen: isolation of a 35-kd recombinant protein (SLA-p35) specifically recognizing sera from patients with autoimmune hepatitis. Hepatology. 2001;33:591-596.
97. Costa M, Rodriguez-Sanchez JL, Czaja AJ, Gelpi C. Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1 autoimmune hepatitis. Clin Exp Immunol. 2000;121:364-374.
98. Gelpi C, Sontheimer EJ, Rodriguez-Sanchez JL. Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion. Proc Natl Acad Sci USA. 1992;89:9739-9743.
99. Baeres M, Herkel J, Czaja AJ, et al. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut. 2002;51:259-264.
100. Czaja AJ, Shums Z, Norman GL. Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis. Autoimmunity. 2002;35:475-483.
101. Ma Y, Okamoto M, Thomas MG, et al. Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology. 2002;35:658-664.
102. Czaja AJ, Donaldson PT, Lohse AW. Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis. Am J Gastroenterol. 2002;97:413-419.
103. Liaskos C, Bogdanos DP, Rigopoulou EI, et al. Antibody responses specific for soluble liver antigen co-occur with Ro-52 autoantibodies in patients with autoimmune hepatitis (abstract). J Hepatol. 2007;46:S250.
104. Eyraud V, Chazouilleres O, Ballot E, et al. Significance of antibodies to soluble liver antigen/liver pancreas: a large French study. Liver Int. 2009;29:857-864.
105. Montano-Loza AJ, Shums Z, Norman GL, Czaja AJ. Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis. Liver Int. 2012;32:85-92.
106. Mix H, Weiler-Normann C, Thimme R, et al. Identification of CD4 T-cell epitopes in soluble liver antigen/liver pancreas autoantigen in autoimmune hepatitis. Gastroenterology. 2008;135: 2107-2118.
107. Czaja AJ. Diverse manifestations and evolving treatments of autoimmune hepatitis. Minerva Gastroenterol Dietol. 2005;51:313-333.
108. Czaja AJ. Special clinical challenges in autoimmune hepatitis: the elderly, males, pregnancy, mild disease, fulminant onset, and nonwhite patients. Semin Liver Dis. 2009;29:315-330.
109. Czaja AJ, Bayraktar Y. Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment. World J Gastroenterol. 2009;15:2314-2328.
110. Czaja AJ. Autoimmune hepatitis in special patient populations. Best Pract Res Clin Gastroenterol. 2011;25:689-700.
111. Lim KN, Casanova RL, Boyer TD, Bruno CJ. Autoimmune hepatitis in African Americans: presenting features and response to therapy. Am J Gastroenterol. 2001;96:3390-3394.
112. Verma S, Torbenson M, Thuluvath PJ. The impact of ethnicity on the natural history of autoimmune hepatitis. Hepatology. 2007;46:1828-1835.
113. Hurlburt KJ, McMahon BJ, Deubner H, et al. Prevalence of autoimmune liver disease in Alaska Natives. Am J Gastroenterol. 2002;97:2402-2407.
114. Minuk GY, Liu S, Kaita K, et al. Autoimmune hepatitis in a North American Aboriginal/First Nations population. Can J Gastroenterol. 2008;22:829-834.
115. Zolfino T, Heneghan MA, Norris S, et al. Characteristics of autoimmune hepatitis in patients who are not of European Caucasoid ethnic origin. Gut. 2002;50:713-717.
116. Nakamura K, Yoneda M, Yokohama S, et al. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J Gastroenterol Hepatol. 1998;13:490-495.
117. Miyakawa H, Kawashima Y, Kitazawa E, et al. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay. J Autoimmun. 2003;21:77-82.
118. Bittencourt PL, Goldberg AC, Cancado EL, et al. Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2. Am J Gastroenterol. 1999;94:1906-1913.
119. Czaja AJ, Souto EO, Bittencourt PL, et al. Clinical distinctions and pathogenic implications of type 1 autoimmune hepatitis in Brazil and the United States. J Hepatol. 2002;37:302-308.
120. Fainboim L, Marcos Y, Pando M, et al. Chronic active autoimmune hepatitis in children. Strong association with a particular HLA-DR6 (DRB1*1301) haplotype. Hum Immunol. 1994;41:146-150.
121. PandoM, Larriba J, Fernandez GC, et al. Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. Hepatology. 1999;30:1374-1380.
122. D'Souza R, Sinnott P, Glynn MJ, Sabin CA, Foster GR. An unusual form of autoimmune hepatitis in young Somalian men. Liver Int. 2005;25:325-330.
123. Nguyen GC, Segev DL, Thuluvath PJ. Racial disparities in the management of hospitalized patients with cirrhosis and complications of portal hypertension: a national study. Hepatology. 2007;45:1282-1289.
124. Nguyen GC, Thuluvath PJ. Racial disparity in liver disease: biological, cultural, or socioeconomic factors. Hepatology. 2008;47:1058-1066.
125. Flores YN, Yee HF Jr, Leng M, et al. Risk factors for chronic liver disease in Blacks, Mexican Americans, and Whites in the United States: results from NHANES IV, 1999-2004. Am J Gastroenterol. 2008;103:2231-2238.
126. Vento S, Garofano T, Di Perri G, et al. Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals. Lancet. 1991;337:1183-1187.
127. Huppertz HI, Treichel U, Gassel AM, Jeschke R. Meyer zum Buschenfelde KH. Autoimmune hepatitis following hepatitis A virus infection. J Hepatol. 1995;23:204-208.
128. Fainboim L, Canero Velasco MC, Marcos CY, et al. Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB*1301, a marker for pediatric autoimmune hepatitis. Hepatology. 2001;33:1512-1517.
129. Muratori P, Czaja AJ, Muratori L, et al. Genetic distinctions between autoimmune hepatitis in Italy and North America. World J Gastroenterol. 2005;11:1862-1866.
130. Muratori P, Czaja AJ, Muratori L, et al. Evidence of a genetic basis for the different geographic occurrences of liver/kidney microsomal antibody type 1 in hepatitis C. Dig Dis Sci. 2007;52:179-184.
131. Manns MP. Autoimmune hepatitis: the dilemma of rare diseases. Gastroenterology. 2011;140:1874-1876.
132. Manns MP, Strassburg CP. Therapeutic strategies for autoimmune hepatitis. Dig Dis. 2011;29:411-415.
133. Turner JD, Thomas AP, Reeves JP, Hantash BM. Calcineurin activation by slow calcium release from intracellular stores suppresses protein kinase C regulation of L-type calcium channels in L6 cells. Cell Calcium. 2009;46:242-247.
134. Martinez-Martinez S, Redondo JM. Inhibitors of the calcineurin/NFAT pathway. Curr Med Chem. 2004;11:997-1007.
135. Serfling E, Berberich-Siebelt F, Avots A, et al. NFAT and NFkappaB factors-the distant relatives. Int J Biochem Cell Biol. 2004;36:1166-1170.
136. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5:472-484.
137. de Jonge H, Naesens M, Kuypers DR. New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit. 2009;31:416-435.
138. Canafax DM, Ascher NL. Cyclosporine immunosuppression. Clin Pharm. 1983;2:515-524.
139. Allison AC. Immunosuppressive drugs: the first 50 years and a glance forward. Immunopharmacology. 2000;47:63-83.
140. Almawi WY, Assi JW, Chudzik DM, Jaoude MM, Rieder MJ. Inhibition of cytokine production and cytokine-stimulated T-cell activation by FK506 (tacrolimus)1. Cell Transplant. 2001;10: 615-623.
141. Iwasaki K. Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet. 2007;22:328-335.
142. Liu J, Farmer JD Jr, Lane WS, et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991;66:807-815.
143. Galat A, Bua J. Molecular aspects of cyclophilins mediating therapeutic actions of their ligands. Cell Mol Life Sci. 2010; 67:3467-3488.
144. Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH. A cytosolic binding protein for the immunosuppressant FK506 has peptidylprolyl isomerase activity but is distinct from cyclophilin. Nature. 1989;341:755-757.
145. Wang T, Donahoe PK, Zervos AS. Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP- 12. Science. 1994;265:674-676.
146. Jorgensen KA, Koefoed-Nielsen PB, Karamperis N. Calcineurin phosphatase activity and immunosuppression. A review on the role of calcineurin phosphatase activity and the immunosuppressive effect of cyclosporin A and tacrolimus. Scand J Immunol. 2003;57:93-98.
147. Pissaia A, Jr, Aoudjehane L, Ben Othman S, et al. Cyclosporine inhibits profibrotic effects of interleukin-4 and transforming growth factor beta on human intrahepatic fibroblasts cultured in vitro. Transplant Proc. 2010;42:4343-4346.
148. Mistilis SP, Vickers CR, Darroch MH, McCarthy SW. Cyclosporin, a new treatment for autoimmune chronic active hepatitis. Med J Aust. 1985;143:463-465.
149. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J Hepatol. 1994;21:1040-1047.
150. Alvarez F, Ciocca M, Canero-Velasco C, et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol. 1999;30:222-227.
151. Cuarterolo M, Ciocca M, Velasco CC, et al. Follow-up of children with autoimmune hepatitis treated with cyclosporine. J Pediatr Gastroenterol Nutr. 2006;43:635-639.
152. Cuarterolo ML, Ciocca ME, Lopez SI, de Davila MT, Alvarez F. Immunosuppressive therapy allows recovery from liver failure in children with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2011;9:145-149.
153. Chatur N, Ramji A, Bain VG, et al. 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;25:723-727.
154. Winkler M, Christians U. A risk-benefit assessment of tacrolimus in transplantation. Drug Saf. 1995;12:348-357.
155. Lohse AW, Weiler-Norman C, Burdelski M. De novo autoimmune hepatitis after liver transplantation. Hepatol Res. 2007;37:S462.
156. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47:85-118.
157. Allison AC. Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14:s2-s8.
158. Morath C, Schwenger V, Beimler J, et al. Antifibrotic actions of mycophenolic acid. Clin Transpl. 2006;20:25-29.
159. Czaja AJ. Mycophenolate mofetil to the rescue in autoimmune hepatitis: a fresh sprout on the decision tree. J Hepatol. 2009;51: 8-10.
160. Adams B, Lazarchick J, Medina AM, et al. Iatrogenic immunodeficiency- associated lymphoproliferative disease of the Hodgkin lymphoma-like variant in a patient treated with mycophenolate mofetil for autoimmune hepatitis. Am J Hematol. 2010;85:627-629.
161. Perez-Aytes A, Ledo A, Boso V, et al. In utero exposure to mycophenolate mofetil: a characteristic phenotype? Am J Med Genet A. 2008;146A:1-7.
162. Anderka MT, Lin AE, Abuelo DN, Mitchell AA, Rasmussen SA. Reviewing the evidence for mycophenolate mofetil as a new teratogen: case report and review of the literature. Am J Med Genet A. 2009;149A:1241-1248.
163. Klieger-Grossmann C, Chitayat D, Lavign S, et al. Prenatal exposure to mycophenolate mofetil: an updated estimate. J Obstet Gynaecol Can. 2010;32:794-797.
164. Lin AE, Singh KE, Strauss A, et al. An additional patient with mycophenolate mofetil embryopathy: cardiac and facial analyses. Am J Med Genet A. 2011;155A:748-756.
165. Seikaly MG. Mycophenolate mofetil - is it worth the cost? The in-favor opinion. Pediatr Transplant. 1999;3:79-82.
166. Heneghan MA, Al-Chalabi T, McFarlane IG. Cost-effectiveness of pharmacotherapy for autoimmune hepatitis. Expert Opin Pharmacother. 2006;7:145-156.
167. Clissold SP, Heel RC. Budesonide. A preliminary review of its pharmacodynamic properties and therapeutic efficacy in asthma and rhinitis. Drugs. 1984;28:485-518.
168. Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology. 2000;119:1312-1316.
169. Geier A, Gartung C, Dietrich CG, et al. 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;9:2681-2685.
170. Efe C, Ozaslan E, Kav T, et al. Liver fibrosis may reduce the efficacy of budesonide in the treatment of autoimmune hepatitis and overlap syndrome. Autoimmun Rev. Epub. 10/06/2011.
171. Lohse AW, Gil H. Reactivation of autoimmune hepatitis during budesonide monotherapy, and response to standard treatment. J Hepatol. 2011;54:837-839.
172. Czaja AJ. Features and consequences of untreated type 1 autoimmune hepatitis. Liver Int. 2009;29:816-823.
173. Feld JJ, Dinh H, Arenovich T, et al. Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology. 2005;42:53-62.
174. Czaja AJ. Difficult treatment decisions in autoimmune hepatitis. World J Gastroenterol. 2010;16:934-947.
175. de Boer NK, van Nieuwkerk CM, Aparicio Pages MN, et al. Promising treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine. Eur J Gastroenterol Hepatol. 2005;17:457-461.
176. Nikolaeva N, Bemelman FJ, Yong SL, van Lier RA, ten Berge IJ. Rapamycin does not induce anergy but inhibits expansion and differentiation of alloreactive human T cells. Transplantation. 2006;81:445-454.
177. Ronis MJ, Butura A, Sampey BP, et al. Effects of N-acetylcysteine on ethanol-induced hepatotoxicity in rats fed via total enteral nutrition. Free Radic Biol Med. 2005;39:619-630.
178. Bemeur C, Vaquero J, Desjardins P, Butterworth RF. N-acetylcysteine attenuates cerebral complications of non-acetaminophen- induced acute liver failure in mice: antioxidant and anti-inflammatory mechanisms. Metab Brain Dis. 2010;25: 241-249.
179. Baumgardner JN, Shankar K, Hennings L, et al. N-acetylcysteine attenuates progression of liver pathology in a rat model of nonalcoholic steatohepatitis. J Nutr. 2008;138:1872-1879.
180. Setshedi M, Longato L, Petersen DR, et al. Limited therapeutic effect of N-acetylcysteine on hepatic insulin resistance in an experimental model of alcohol-induced steatohepatitis. Alcohol Clin Exp Res. Epub. 07/28/2011.
181. Desai D, Kaushal N, Gandhi UH, et al. Synthesis and evaluation of the anti-inflammatory properties of selenium-derivatives of celecoxib. Chem Biol Interact. 2010;188:446-456.
182. Smith CA, Williams GT, Kingston R, Jenkinson EJ, Owen JJ. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989;337:181-184.
183. von Herrath MG, Coon B, Wolfe T, Chatenoud L. Nonmitogenic CD3 antibody reverses virally induced (rat insulin promoterlymphocytic choriomeningitis virus) autoimmune diabetes without impeding viral clearance. J Immunol. 2002;168: 933-941.
184. Chatenoud L. Anti-CD3 antibodies: towards clinical antigenspecific immunomodulation. Curr Opin Pharmacol. 2004;4: 403-407.
185. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces
186. Herold KC, Hagopian W, Auger JA, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002;346:1692-1698.
187. Herold KC, Gitelman SE, Masharani U, et al. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005;54:1763-1769.
188. Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC. Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature. 2001;410:604-608.
189. Scalapino KJ, Daikh DI. CTLA-4: a key regulatory point in the control of autoimmune disease. Immunol Rev. 2008;223: 143-155.
190. Weyand CM, Goronzy JJ. T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2:201-210.
191. Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009:CD007277.
192. Chen W, Perruche S, Li J. CD4+ CD25+ T regulatory cells and TGF-beta in mucosal immune system: the good and the bad. Curr Med Chem. 2007;14:2245-2249.
193. Longhi MS, Ma Y, Bogdanos DP, et al. Impairment of CD4(?)CD25(?) regulatory T-cells in autoimmune liver disease. J Hepatol. 2004;41:31-37.
194. Longhi MS, Hussain MJ, Mitry RR, et al. Functional study of CD4? CD25? regulatory T cells in health and autoimmune hepatitis. J Immunol. 2006;176:4484-4491.
195. Longhi MS, Meda F, Wang P, et al. Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis. Hepatology. 2008;47: 581-591.
196. Jacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997;84:223-243.
197. Kim WR, Brown RS Jr, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology. 2002;36:227-242.