Liver Failure and Liver Disease

You have full text access to this OnlineOpen article

Autoimmune hepatitis, from mechanisms to therapy†

  1. Michael P. Manns*,
  2. Arndt Vogel

Article first published online: 30 JAN 2006

DOI: 10.1002/hep.21059

Issue

Hepatology

Hepatology

Special Issue: 25th Anniversary Issue

Volume 43, Issue S1, pages S132–S144, February 2006

Additional Information

How to Cite

Manns, M. P. and Vogel, A. (2006), Autoimmune hepatitis, from mechanisms to therapy. Hepatology, 43: S132–S144. doi: 10.1002/hep.21059

Author Information

  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany

*Professor and Chairman, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neubergstr. 1, 30625 Hannover, Germany

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 30 JAN 2006
  2. Article first published online: 30 JAN 2006

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (336K)

References

  • 1
    Desmet VJ, Gerber M, Hoofnaagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513–1520.
    Direct Link:
  • 2
    Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999; 31: 929–938.
  • 3
    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.
    Direct Link:
  • 4
    Gregorio GV, Portman B, Reid F, Donaldson PT, Doherty DG, McCartney M, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25: 541–547.
    Direct Link:
  • 5
    Czaja AJ, Muratori P, Muratori L, Carpenter HA, Bianchi FB. Diagnostic and therapeutic implications of bile duct injury in autoimmune hepatitis. Liver Int 2004; 24: 322–329.
    Direct Link:
  • 6
    Donaldson PT. Genetics in autoimmune hepatitis. Semin Liver Dis 2002; 22: 353–364.
  • 7
    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: 537–542.
  • 8
    Talwalkar JA, Keach JC, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system. Am J Gastroenterol 2002; 97: 1191–1197.
    Direct Link:
  • 9
    Kirk AP, Jain S, Pocock S, Thomas HC, Sherlock S. Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut 1980; 21: 7893.
  • 10
    Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. Q J Med 1971; 40: 159–185.
  • 11
    Murray- Lyon IM, Stern RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet 1973; I: 735–737.
  • 12
    Read AE, Sherlock S, Harrison CV. Active juvenile cirrhosis considered as part of a systemic disease associated and the effect of corticosteroid therapy. Gut 1963; 4: 378–393.
  • 13
    Roberts SK, Therneau TM, Czaja AJ. Prognosis of histological cirrhosis in type 1 autoimmune hepatitis. Gastroenterology 1996; 110: 848–857.
  • 14
    Kogan J, Safadi R, Ashur Y, Shouval D, Ilan Y. Prognosis of symptomatic versus asymptomatic autoimmune hepatitis: a study of 68 patients. J Clin Gastroenterol 2002; 35: 75–81.
  • 15
    Czaja AJ, Carpenter HA. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol 2004; 40: 646–652.
  • 16
    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.
    Direct Link:
  • 17
    Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirth S. Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis. J Autoimmun 2005; 24: 79–84.
  • 18
    Homberg JC, Abuaf N, Bernard ON, Islam S, Alvarez F, Khalil SH, et al. Chronic active hepatitis associated with anti liver/kidney microsome type 1: a second type of “autoimmune” hepatitis. Hepatology 1987; 7: 1333–1339.
    Direct Link:
  • 19
    Schramm C, Kanzler S, zum Buschenfelde KH, Galle PR, Lohse AW. Autoimmune hepatitis in the elderly. Am J Gastroenterol 2001; 96: 1587–1591.
    Direct Link:
  • 20
    Granito A, Muratori L, Pappas G, Muratori P, Ferri S, Cassani F, et al. Clinical features of type 1 autoimmune hepatitis in elderly Italian patients. Aliment Pharmacol Ther 2005; 21: 1273–1277.
    Direct Link:
  • 21
    Verslype C, George C, Buchel E, Nevens F, van Steenbergen W, Fevery J. Diagnosis and treatment of autoimmune hepatitis at age 65 and older. Aliment Pharmacol Ther 2005; 21: 695–699.
    Direct Link:
  • 22
    Newton JL, Burt AD, Park JB, Mathew J, Bassendine MF, James OF. Autoimmune hepatitis in older patients. Age Ageing 1997; 26: 441–444.
  • 23
    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.
    Direct Link:
  • 24
    Pando M, Larriba J, Fernandez GC, Fainboim H, Ciocca M, Ramonet M, et al. Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. Hepatology 1999; 30: 1374–1380.
    Direct Link:
  • 25
    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: 713–717.
  • 26
    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: 2402–2407.
    Direct Link:
  • 27
    Broome UO, Loof R, Bodemar L, Hultcrantz G, Danielsson R, Prytz A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 1996; 38: 610–615.
  • 28
    Park SZ, Nagorney DM, Czaja AJ. Hepatocellular carcinoma in autoimmune hepatitis. Dig Dis Sci 2000; 45: 1944–1948.
  • 29
    Gregorio GV, McFarlane B, Bracken P, Vergani D, Mieli-Vergani G. Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease. Autoimmunity 2002; 35: 515–519.
  • 30
    Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 2004; 41: 677–683.
  • 31
    Czaja AJ, Shums Z, Donaldson PT, Norman GL. Frequency and significance of antibodies to Saccharomyces cerevisiae in autoimmune hepatitis. Dig Dis Sci 2004; 49: 611–618.
  • 32
    Czaja AJ, Shums Z, Binder WL, Lewis SJ, Nelson VJ, Norman GL. Frequency and significance of antibodies to chromatin in autoimmune hepatitis. Dig Dis Sci 2003; 48: 1658–1664.
  • 33
    Liaskos C, Rigopoulou E, Zachou K, Georgiadou S, Gatselis N, Papamihali R, et al. Prevalence and clinical significance of anticardiolipin antibodies in patients with type 1 autoimmune hepatitis. J Autoimmun 2005; 24: 251–260.
  • 34
    Strassburg CP, Manns MP. Autoantibodies and autoantigens in autoimmune hepatitis. Semin Liver Dis 2002; 22: 339–352.
  • 35
    Adams LA, Lindor KD, Angulo P. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic Fatty liver disease. Am J Gastroenterol 2004; 99: 1316–1320.
    Direct Link:
  • 36
    Czaja AJ, Nishioka M, Morhed SA, Haciya T. Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis. Gastroenterology 1994; 107: 200–207.
  • 37
    Strassburg CP, Alex B, Zindy F, Gerken G, Luttig B, Meyer zum Buschenfelde KH, et al. Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune diseases. J Hepatol 1996; 25: 859–866.
  • 38
    Czaja AJ, Cassani F, Cataleta M, Valentini P, Bianchi FB. Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis. Hepatology 1996; 24: 1068–1073.
    Direct Link:
  • 39
    Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and other disorders. Clin. Exp. Immunol. 1973; 15: 331–344.
  • 40
    Zanger UM, Hauri HP, Loeper J, Homberg JC, Meyer UA. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type 2. Proc. Natl. Acad. Sci. USA 1988; 85: 8256–8260.
  • 41
    Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF. Major antigen of liver kidney microsomal antibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J. Clin. Invest. 1989; 83: 1066–1072.
  • 42
    Manns MP, Griffin KJ, Sullivan KF, Johnson EF. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. J. Clin. Invest. 1991; 88: 1370–1378.
  • 43
    Yamamoto AM, Cresteil D, Boniface O, Clerc FF, Alvarez F. Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (LKM1). Eur. J. Immunol. 1993; 23: 1105–1111.
    Direct Link:
  • 44
    Klein R, Zanger UM, Berg T, Hopf U, Berg PA. Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes. Clin Exp Immunol 1999; 118: 290–297.
    Direct Link:
  • 45
    Kerkar N, Choudhuri K, Ma Y, Mahmoud A, Bogdanos DP, Muratori L, et al. Cytochrome P4502D6(193-212): A New Immunodominant Epitope and Target of Virus/Self Cross-Reactivity in Liver Kidney Microsomal Autoantibody Type 1-Positive Liver Disease. J Immunol 2003; 170: 1481–1489.
  • 46
    Sugimura T, Obermayer-Straub P, Kayser A, Braun S, Loges S, Alex B, et al. A major CYP2D6 autoepitope in autoimmune hepatitis type 2 and chronic hepatitis C is a three-dimensional structure homologous to other cytochrome P450 autoantigens. Autoimmunity 2002; 35: 501–513.
  • 47
    Ma Y, Thomas MG, Okamoto M, Bogdanos DP, Nagl S, Kerkar N, et al. Key residues of a major cytochrome P4502D6 epitope are located on the surface of the molecule. J Immunol 2002; 169: 277–285.
  • 48
    Marceau G, Lapierre P, Beland K, Soudeyns H, Alvarez F. LKM1 autoantibodies in chronic hepatitis C infection: a case of molecular mimicry? Hepatology 2005; 42: 675–682.
    Direct Link:
  • 49
    Bogdanos DP, Lenzi M, Okamoto M, Rigopoulou EI, Muratori P, Ma Y, et al. Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus infected patients is associated with the possession of HLA B51. Int J Immunopathol Pharmacol 2004; 17: 83–92.
  • 50
    Lapierre P, Djilali-Saiah I, Vitozzi S, Alvarez F. A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens. Hepatology 2004; 39: 1066–1074.
    Direct Link:
  • 51
    Christen U, Rhode A, Johnson E, Manns MP, von Herrath MG. Development of an animal model for autoimmune hepatitis: Breaking of self-tolerance in the CYP2D6 humanized mouse by viral infection. Hepatology 2004; 38.
  • 52
    Ticrynafen recalled. FDA Drug Bull 1980; 10: 3-4.
  • 53
    Strassburg CP, Obermayer-Straub P, Alex B, Durazzo M, Rizzetto M, Tukey RH, et al. Autoantibodies against glucuronosyltransferases differ between viral hepatitis and autoimmune hepatitis. Gastroenterology 1996; 111: 1576–1586.
  • 54
    Obermayer-Straub P, Strassburg C, Clemente M-G, Philipp T, Tukey RH, Manns MP. Recognition of three different epitopes on UDP-glucuronosyltransferases by LKM-3 antibodies in patients with autoimmune hepatitis and hepatitis D. Gut 1995; 37(2): A100.
  • 55
    Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, Jet al. Recognition of uridine diphosphate glucuronosyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 1994; 344: 578–581.
  • 56
    Csepregi A, Nemesanszky E, Luettig B, Obermayer-Straub P, Manns MP. LKM3 autoantibodies in hepatitis C cirrhosis: a further phenomenon of the HCV-induced autoimmunity. Am J Gastroenterol 2001; 96: 910–911.
    Direct Link:
  • 57
    Gelpi C SE, Rodriguez-Sanchez JL. Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion. Proc Natl Acad Sci U S A 1992; 89: 9739–9743.
  • 58
    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.
  • 59
    Volkmann M, Martin L, Baurle A, Heid H, Strassburg CP, Trautwein C, 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.
    Direct Link:
  • 60
    Wies I, Brunner S, Henninger J, Herkel J, Kanzler S, Meyer zum Buschenfelde KH, Lohse AW. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis [see comments]. Lancet 2000; 355: 1510–1515.
  • 61
    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.
    Direct Link:
  • 62
    Vitozzi S, Lapierre P, Djilali-Saiah I, Marceau G, Beland K, Alvarez F. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection. Autoimmunity 2004; 37: 217–222.
  • 63
    Ma Y, Okamoto M, Thomas MG, Bogdanos DP, Lopes AR, Portmann B, et al. Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology 2002; 35: 658–664.
    Direct Link:
  • 64
    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.
    Direct Link:
  • 65
    Herkel J, Heidrich B, Nieraad N, Wies I, Rother M, Lohse AW. Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas. Hepatology 2002; 35: 403–408.
    Direct Link:
  • 66
    Han S, Tredger M, Gregorio GV, Mieli-Vergani G, Vergani D. Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease. Hepatology 1995; 21: 58–62.
  • 67
    Lenzi M, Manotti P, Muratori L, Cataleta M, Ballardini G, Cassani F, et al. Liver cytosolic 1 antigen-antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. Gut 1995; 36: 749–754.
  • 68
    Martini E, Abuaf N, Cavalli F, Durand V, Johanet C, Homberg JC. Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology 1988; 8: 1662–1666.
    Direct Link:
  • 69
    Lapierre P, Hajoui O, Homberg J-C, Alvarez F. Fomiminotransferase cyclodeaminase is an organ specific autoantigen recognized by sera of patients with autoimmune hepatitis. Gastroenterology 1999; 116: 643–649.
  • 70
    Kohls D, Sulea T, Purisima EO, MacKenzie RE, Vrielink A. The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme. Structure Fold Des 2000; 8: 35–46.
  • 71
    Lapierre P, Johanet C, Alvarez F. Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis. Eur J Immunol 2003; 33: 1869–1878.
    Direct Link:
  • 72
    Beland K, Lapierre P, Marceau G, Alvarez F. Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection. J Autoimmun 2004; 22: 159–166.
  • 73
    Muratori L, Cataleta M, Muratori P, Lenzi M, Bianchi FB. Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis. Gut 1998; 42: 721–726.
  • 74
    Treichel U, Gerken G, Rossol S, Rotthaue HW, Meyer zum Büschenfelde K-H, Portalla T. Autoantibodies against the human asialoglycoprotein receptor: Effects of therapy in autoimmune and virus-induced chronic active hepatitis. J. Hepatology 1993; 19: 55–63.
  • 75
    McFarlane IG, Hegarty JE, McSorley CG, McFarlane BM, Williams R. Antibodies to liver-specific protein predict outcome of treatment withdrawal in autoimmune chronic active hepatitis. Lancet 1984; 2: 954–956.
  • 76
    Treichel U, Poralla T, Hess G, Manns M, Meyer zum Buschenfelde KH. Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology 1990; 11: 606–612.
    Direct Link:
  • 77
    Czaja AJ, Pfeifer KD, Decker RH, Vallari AS. Frequency and significance of antibodies to asialoglycoprotein receptor in type 1 autoimmune hepatitis. Dig. Dis. Sci. 1996; 41: 1733–1740.
  • 78
    Czaja AJ, Manns MP, Homburger HA. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology 1992; 103: 1290–1295.
  • 79
    Czaja AJ. Behavior and significance of autoantibodies in type 1 autoimmune hepatitis. J Hepatol 1999; 30: 394–401.
  • 80
    Kanzler S, Weidemann C, Gerken G, Lohr HF, Galle PR, Meyer zum Buschenfelde KH, et al. Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis. J Hepatol 1999; 31: 635–640.
  • 81
    Czaja AJ, Shums Z, Norman GL. Nonstandard antibodies as prognostic markers in autoimmune hepatitis. Autoimmunity 2004; 37: 195–201.
  • 82
    Baeres M, Herkel J, Czaja AJ, Wies I, Kanzler S, Cancado EL, et al. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut 2002; 51: 259–264.
  • 83
    Regner M, Lambert PH. Autoimmunity through infection or immunization? Nat Immunol 2001; 2: 185–188.
  • 84
    Ermann J, Fathman CG. Autoimmune diseases: genes, bugs and failed regulation. Nat Immunol 2001; 2: 759–761.
  • 85
    Donaldson PT. Genetics of autoimmune and viral liver diseases; understanding the issues. J Hepatol 2004; 41: 327–332.
  • 86
    Donaldson PT. Genetics of liver disease: immunogenetics and disease pathogenesis. Gut 2004; 53: 599–608.
  • 87
    Klein J, Sato A. The HLA system. First of two parts. N Engl J Med 2000; 343: 702–709.
  • 88
    Klein J, Sato A. The HLA system. Second of two parts. N Engl J Med 2000; 343: 782–786.
  • 89
    Strettel MDJ, Donaldson PT, Thomson LJ, Santrach PJ, Brenndan Moore S, Czaja AJ, et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 1997; 112: 2028–2035.
  • 90
    Czaja AJ, Strettell M, Thomson LJ, Santrach P, Moore SB, Donaldson PT, et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology 1997; 25: 317–323.
    Direct Link:
  • 91
    Czaja AJ, Carpenter HA, Santrach PJ, Moore SB. Significance of HLA DR4 in type 1 autoimmune hepatitis. Gastroenterology 1993; 105: 1502–1507.
  • 92
    Donaldson P, Doherty D, Underhill J, Williams R. The molecular genetics of autoimmune liver disease. Hepatology 1994; 20: 225–229.
    Direct Link:
  • 93
    Scully LJ, Toze C, Sengar DPS, Goldstein R. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology 1993; 104: 1478–1484.
  • 94
    Czaja AJ, Cookson S, Constantini PK, Clare M, Underhill JA, Donaldson PT. Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis. Gastroenterology 1999; 117: 645–652.
  • 95
    Cookson S, Constantini PK, Clare M, Underhill JA, Bernal W, Czaja AJ, et al. Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis. Hepatology 1999; 30: 851–856.
    Direct Link:
  • 96
    Bittencourt PL, Palacios SA, Cancado EL, Porta G, Drigo S, Carrilho FJ, et al. Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor alpha polymorphisms at position -308. J Hepatol 2001; 35: 24–28.
  • 97
    Agarwal K, Czaja AJ, Jones DE, Donaldson PT. Cytotoxic T lymphocyteantigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis. Hepatology 2000; 31: 49–53.
    Direct Link:
  • 98
    Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506–511.
  • 99
    Djilali-Saiah I, Ouellette P, Zucman S, Caillat-Debray D, Kohn JI, Alvarez F. CTLA-4/CD 28 region polymorphisms in children from families with autoimmune hepatitis. Hum Immunol 2001; 62: 1356–1362.
  • 100
    Bittencourt PL, Palacios SA, Cancado EL, Porta G, Carrilho FJ, Laudanna AA, et al. Cytotoxic T lymphocyte antigen-4 gene polymorphisms do not confer susceptibility to autoimmune hepatitis types 1 and 2 in Brazil. Am J Gastroenterol 2003; 98: 1616–1620.
  • 101
    Hiraide A, Imazeki F, Yokosuka O, Kanda T, Kojima H, Fukai K, et al. Fas polymorphisms influence susceptibility to autoimmune hepatitis. Am J Gastroenterol 2005; 100: 1322–1329.
    Direct Link:
  • 102
    Fan LY, Tu XQ, Zhu Y, Pfeiffer T, Feltens R, Stoecker W, et al. Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. World J Gastroenterol 2005; 11: 2768–2772.
  • 103
    Fan L, Tu X, Zhu Y, Zhou L, Pfeiffer T, Feltens R, et al. Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese. J Gastroenterol Hepatol 2005; 20: 249–255.
    Direct Link:
  • 104
    Vogel A, Strassburg CP, Manns MP. Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 2002; 35: 126–131.
    Direct Link:
  • 105
    Vogel A, Strassburg CP, Manns MP. 77 C/G mutation in the tyrosine phosphatase CD45 gene and autoimmune hepatitis: evidence for a genetic link. Genes Immun 2003; 4: 79–81.
  • 106
    Esteghamat F, Noorinayer B, Sanati MH, Hekmatdoost A, Zafarghandi M, Shalmani HM, et al. C77G mutation in protein tyrosine phosphatase CD45 gene and autoimmune hepatitis. Hepatol Res 2005.
  • 107
    Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990; 322: 1829–1836.
  • 108
    Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nat Genet 1997; 17: 393–398.
  • 109
    Vogel A, Strassburg CP, Obermayer-Straub P, Brabant G, Manns MP. The genetic background of autoimmune polyendocrinopathy-candidiasis-Ectodermal dystrophy and its autoimmune disease components. J Mol Med 2002; 80: 201–210.
  • 110
    Podkrajsek KT, Bratanic N, Krzisnik C, Battelino T. AIRE-1 mRNA Analysis in a Novel Intronic Mutation and Two Additional Novel AIRE Gene Mutations in a Cohort of APECED Patients. J Clin Endocrinol Metab 2005.
  • 111
    Vogel A, Liermann H, Harms A, Strassburg CP, Manns MP, Obermayer-Straub P. Autoimmune regulator AIRE: Evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1. Hepatology 2001; 33: 1047–1052.
    Direct Link:
  • 112
    Djilali-Saiah I, Renous R, Caillat-Zucman S, Debray D, Alvarez F. Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients. J Hepatol 2004; 40: 904–909.
  • 113
    Clemente MG, Obermayer-Straub P, Meloni A, Strassburg CP, Arangino V, Tukey RH, et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1997; 82: 1353–1361.
  • 114
    Clemente MG, Meloni A, Obermayer-Straub P, Frau F, Manns MP, De Virgiliis S. Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1. Gastroenterology 1998; 114: 324–328.
  • 115
    Obermayer-Straub P, Perheentupa J, Braun S, Kayser A, Barut A, Loges S, et al. Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Gastroenterology 2001; 121: 668–677.
  • 116
    Soderbergh A, Myhre AG, Ekwall O, Gebre-Medhin G, Hedstrand H, Landgren E, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 2004; 89: 557–562.
  • 117
    Czaja AJ, Rakela J, Ludwig J. Features reflective of early prognosis in corticosteroid-treated severe autoimmune chronic active hepatitis. Gastroenterology 1988; 95: 448–453.
  • 118
    Cooksley WGE, Bradbear RA, Robinson W, Harrison M, Halliday JW, Powell LW, et al. The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis. Hepatology 1986; 6: 345–348.
    Direct Link:
  • 119
    Czaja AJ. Drug therapy in the management of type 1 autoimmune hepatitis. Drugs 1999; 57: 49–68.
  • 1120
    Manns MP, Strassburg CP: Autoimmune Hepatitis. In: O'GradyJG, LakeJR, HowdleDP, eds. Comprehensive Clinical Hepatology. London: Mosby, 2000; 16.11–14.
  • 121
    Sanchez-Urdazpal L, Czaja AJ, Van Holk B. Prognostic features and role of liver transplantation in severe corticoid-treated autoimmune chronic active hepatitis. Hepatology 1991; 15: 215–221.
    Direct Link:
  • 122
    Czaja AJ, Davis GL, Ludwig J, Baggenstoss AH, Taswell HF. Autoimmune features as determinants of prognosis in steroid-treated chronic active hepatitis of uncertain etiology. Gastroenterology 1983; 85: 713–717.
  • 123
    Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology 2002; 36: 479–497.
    Direct Link:
  • 124
    Czaja AJ. Treatment of autoimmune hepatitis. Semin Liver Dis 2002; 22: 365–378.
  • 125
    Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001; 120: 1502–1517.
  • 126
    Summerskill WHJ, Korman MG, Ammon HV, Baggenstoss AH. Prednisone for chronic active liver disease: dose titration, standard dose and combination with azathioprine compound. Gut 1975; 16: 876–883.
  • 127
    Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002; 35: 7–13.
    Direct Link:
  • 128
    Danielson A, Prytz H. Oral budesonide for treatment of autoimmune chronic hepatitis. Aliment. Pharmacol. Ther. 1994; 8: 585–590.
    Direct Link:
  • 129
    Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment-dependent autoimmune hepatitis. Gastroenterology 2000; 119: 1312–1316.
  • 130
    Rebollo Bernardez J, Cifuentes Mimoso C, Pinar Moreno A, Caunedo Alvarez A, Salas Herrero E, Jimenez-Saenz M, et al. Deflazacort for long-term maintenance of remission in type I autoimmune hepatitis. Rev Esp Enferm Dig 1999; 91: 630–638.
  • 131
    Alvarez F, Ciocca M, Canero-Velasco C, Ramonet M, de Davila.MTG, Cuarterolo M, et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J. Hepatol 1999; 30: 222–227.
  • 132
    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.
  • 133
    Kanzler S, Gerken G, Dienes HP, Meyer zum Büschenfelde K-H, Lohse AW. Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis - report of three cases. Z. Gastroenterol. 1996; 35: 571–578.
  • 134
    Calmus Y, Gane P, Rouger P, Poupon R. Hepatic expression of class I and class II major histocompatibility complex molecules in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology 1990; 11: 12–15.
    Direct Link:
  • 135
    Nakamura K, Yoneda M, Yokohama S, Tamori K, Sato Y, Aso K, et al. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis [see comments]. J Gastroenterol Hepatol 1998; 13: 490–495.
    Direct Link:
  • 136
    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: 1381–1386.
    Direct Link:
  • 137
    van Hoogstraten HJ, Vleggaar FP, Boland GJ, van Steenbergen W, Griffioen P, Hop WC, et al. Budesonide or prednisone in combination with ursodeoxycholic acid in primary sclerosing cholangitis: a randomized double-blind pilot study. Belgian-Dutch PSC Study Group [see comments]. Am J Gastroenterol 2000; 95: 2015–2022.
  • 138
    Wiegand J, Schuler A, Kanzler S, Lohse A, Beuers U, Kreisel W, et al. Budesonide in previously untreated autoimmune hepatitis. Liver Int 2005; 25: 927–934.
    Direct Link:
  • 139
    Samuel D, Figueiro J, Bismuth H. Liver transplantation: Indications and Patient Selection. London: Mosby, 2000: 34.31–34.17.
  • 140
    Tan P, Marotta P, Ghent C, Adams P. Early treatment response predicts the need for liver transplantation in autoimmune hepatitis. Liver Int 2005; 25: 728–733.
    Direct Link:
  • 141
    Vogel A, Heinrich E, Bahr MJ, Rifai K, Flemming P, Melter M, et al. Long-term outcome of liver transplantation for autoimmune hepatitis. Clin Transplant 2004; 18: 62–69.
    Direct Link:
  • 142
    Duclos-Vallee JC, Sebagh M, Rifai K, Johanet C, Ballot E, Guettier C, et al. A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence. Gut 2003; 52: 893–897.
  • 143
    Reich DJ, Fiel I, Guarrera JV, Emre S, Guy SR, Schwartz ME, et al. Liver transplantation for autoimmune hepatitis. Hepatology 2000; 32: 693–700.
    Direct Link:
  • 144
    Wright HL, Bou-Abboud CF, Hassanenstein T, Block GD, Demetris AJ, Starzl TE, et al. Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease. Transplantation 1992; 53: 136–139.
  • 145
    Prados E, Cuervas-Mons V, De La Mata M, Fraga E, Rimola A, Prieto M, et al. Outcome of autoimmune hepatitis after liver transplantation. Transplantation 1998; 66: 1645–1650.
  • 146
    Gonzalez-Koch A, Czaja AJ, Carpenter HA, Roberts SK, Charlton MR, Porayko MK, et al. Recurrent autoimmune hepatitis after orthotopic liver transplantation. Liver Transpl 2001; 7: 302–310.
    Direct Link:
  • 147
    Götz G, Neuhaus R, Bechstein WO, Lobeck H, Berg T, Hopf U, et al. Recurrence of autoimmune hepatitis after liver transplantation. Transplant. Proc. 1999; 31: 430–431.
  • 148
    Milkiewicz P, Hubscher SG, Skiba G, Hathaway M, Elias E. Recurrence of autoimmune hepatitis after liver transplantation. Transplantation 1999; 68: 253–256.
  • 149
    Ratziu V, Samuel D, Sebagh M, Farges O, Saliba F, Ichai P, et al. Long-term follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease. J Hepatol 1999; 30: 131–141.
  • 150
    Dmitrewski J, Hubscher SG, Mayer AD, Neuberger JM. Recurrence of primary biliary cirrhosis in the liver allograft: the effect of immunosuppression. J Hepatol 1996; 24: 253–257.
  • 151
    Andries S, Casamayou L, Sempoux C, Burlet M, Reding R, Bernard Otte J, et al. Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine. Transplantation 2001; 72: 267–272.
  • 152
    Salcedo M, Vaquero J, Banares R, Rodriguez-Mahou M, Alvarez E, Vicario JL, et al. Response to steroids in de novo autoimmune hepatitis after liver transplantation. Hepatology 2002; 35: 349–356.
    Direct Link:
  • 153
    Kerkar N, Dugan C, Rumbo C, Morotti RA, Gondolesi G, Shneider BL, et al. Rapamycin successfully treats post-transplant autoimmune hepatitis. Am J Transplant 2005; 5: 1085–1089.
    Direct Link:
  • 154
    Kerkar N, Hadzic N, Davies ET, Portmann B, Donaldson PT, Rela M, et al. De-novo autoimmune hepatitis after liver transplantation. Lancet 1998; 351: 409–413.
  • 155
    Miyagawa-Hayashino A, Haga H, Egawa H, Hayashino Y, Sakurai T, Minamiguchi S, et al. Outcome and risk factors of de novo autoimmune hepatitis in living-donor liver transplantation. Transplantation 2004; 78: 128–135.
  • 156
    Heneghan MA, Portmann BC, Norris SM, Williams R, Muiesan P, Rela M, et al. Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults. Hepatology 2001; 34: 464–470.
    Direct Link:
  • 157
    Mieli-Vergani G, Vergani D. De novo autoimmune hepatitis after liver transplantation. J Hepatol 2004; 40: 3–7.
  • 158
    Aguilera I, Sousa JM, Gavilan F, Bernardos A, Wichmann I, Nunez-Roldan A. Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation. Liver Transpl 2004; 10: 1166–1172.
    Direct Link:
  • 159
    Shankarkumar U, Pitchappan R, Pethaperumal S. Human leukocyte antigens in hypertrophic cardiomyopathy patients in South India. Asian Cardiovasc Thorac Ann 2004; 12: 107–110.
  • 160
    Vazquez-Garcia MN, Alaez C, Olivo A, Debaz H, Perez-Luque E, Burguete A, et al. MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis. J. Hepatol 1998; 28: 985–990.
  • 161
    Yoshizawa K, Ota M, Katsuyama Y, Ichijo T, Matsumoto A, Tanaka E, et al. Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis. J Hepatol 2005; 42: 578–584.
View Full Article (HTML) Get PDF (336K)