Autoimmune hepatitis

Česká verzia

Authors: Petr Urbánek
Authors place of work: Interní klinika 1. LF UK a ÚVN Praha
Published in the journal: Vnitř Lék 2020; 66(1): 36-43
Category:

Summary

Autoimmune hepatitis is a chronic inflammatory disease of hepatic tissue of unknown aetiology characterized by serological reactivity of various types of autoantibodies and hypergammaglobulinaemia. It predominantly affects younger or middle-aged women. If untreated, in the majority of cases there occurs gradual disease progression and development of liver cirrhosis with all its consequences. Clinical manifestations are not uniform, with several manifestation phenotypes having been identified: acute hepatocellular injury resembling acute viral hepatitis; more rarely, a manifestation in the form of fulminant hepatitis; most commonly, however, the disease has a silent clinical course, with a chronic mild elevation in serum hepatic transaminase activity being the only possible sign of liver disease. In clinically less obvious cases, recognition of the disease may be a diagnostic challenge. In these cases, several scoring systems can be used that effectively aid in diagnosing the condition. The therapeutic goal is to achieve a complete response defined as full normalization of the serum ALT and AST activities, as well as normalization of serum gamma globulin concentration. The treatment is divided into two phases: induction and maintenance. The administration of prednisone in monotherapy or in combination with azathioprine is the basic procedure in both phases. Relapses are very frequent when treatment is discontinued, with as many as 80% of the patients having a relapse within three years.

Keywords:

liver cirrhosis – autoimmune hepatitis – immunosuppressive therapy

Zdroje

1. Liberal R, Krawitt EL, Vierling JM, et al. Cutting edge issues in autoimmune hepatitis. J Autoimmun 2016; 75: 6–19.

2. Leber WJ. Blutproteine und Nahrungseiweiss (Liver, blood pro-teins and nutritive protein). Dtsch Z Verdau Stoffwechselkr 1953; 9: 113–119.

3. Cowling DC, Mackay IR, Taft LI. Lupoid hepatitis. Lancet 1956; 271: 1323–1326.

4. Mackay IR, Weiden S, Hasker J. Autoimmune hepatitis. Ann NY Acad Sci 1965; 124: 767–780.

5. Kirk AP, Jain S, Pocock S, et al. 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: 78–83.

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

7. Czaja AJ, Bayraktar Y. Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment. World J Gastroenterol 2009; 15: 2314–2328.

8. Al-Chalabi T, Underhill JA, Portmann BC, et al. Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis. J Hepatol 2008; 48: 140–147.

9. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010; 51: 2193–2213.

10. Stravitz RT, Lefkowitch JH, Fontana RJ, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011; 53: 517–526.

11. Fujiwara K, Fukuda Y, Yokosuka O. Precise histological evaluation of liver biopsy specimen is indispensable for diagnosis and treatment of acute-onset autoimmune hepatitis. J Gastroenterol 2008; 43: 951–958.

12. Yasui S, Fujiwara K, Yonemitsu Y, et al. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol 2011; 46: 378–390.

13. Kogan J, Safadi R, Ashur Y, et al. Prognosis of symptomatic versus asymptomatic autoimmune hepatitis: a study of 68 patients. J Clin Gastroenterol 2002; 35: 75–81.

14. Czaja AJ. Features and consequences of untreated type 1 autoimmune hepatitis. Liver Int 2009; 29: 816–823.

15. Czaja AJ, Carpenter HA, Santrach PJ, et al. The nature and prognosis of severe cryptogenic chronic active hepatitis. Gastroenterology 1993; 104: 1755–1761.

16. Heringlake S, Schütte A, Flemming P, et al. Presumed cryptogenic liver disease in Germany: high prevalence of autoantibody-negative autoimmune hepatitis, low prevalence of NASH, no evidence for occult viral etiology. Z Gastroenterol 2009; 47: 417–423.

17. Czaja AJ. Behavior and significance of autoantibodies in type 1autoimmune hepatitis. J Hepatol 1999; 30: 394–401.

18. Prasad KK, Debi U, Sinha SK, et al. Hepatobiliary disorders in celiac disease: an update. Int J Hepatol 2011; 2011: 438184.

19. Gassert DJ, Garcia H, Tanaka K, et al. Corticosteroid-responsive cryptogenic chronic hepatitis: evidence for seronegative autoimmune hepatitis. Dig Dis Sci 2007; 52: 2433–2437.

20. Miyake Y, Iwasaki Y, Terada R, et al. Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis. Hepatol Res 2007; 37: 801–805.

21. Kessler WR, Cummings OW, Eckert G, et al. Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis. Clin Gastroenterol Hepatol 2004; 2: 625–631.

22. Czaja AJ, Carpenter HA. Autoimmune hepatitis with incidental histologic features of bile duct injury. Hepatology 2001; 34: 659–665.

23. Angulo P, Maor-Kendler Y, Lindor KD. Small-duct primary sclerosing cholangitis: a long-term follow-up study. Hepatology 2002; 35: 1494–1500.

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

25. Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol 2014; 12: 1430–1438.

26. Kim WR, Ludwig J, Lindor KD. Variant forms of cholestatic diseases involving small bile ducts in adults. Am J Gastroenterol 2000; 95: 1130–1138.

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

28. Gatselis NK, Zachou K, Papamichalis P, et al. 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: 807–812.

29. Homberg JC, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of „autoimmune” hepatitis. Hepatology 1987; 7: 1333–1339.

30. Gleeson D, Heneghan MA. British Society of Gastroenterology. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut 2011; 60: 1611–1629.

31. Czaja AJ, Manns MP. The validity and importance of subtypes in autoimmune hepatitis: a point of view. Am J Gastroenterol 1995; 90: 1206–1211.

32. Muratori P, Lalanne C, Fabbri A, et al. Type 1 and type 2 autoimmune hepatitis in adults share the same clinical phenotype. Aliment Pharmacol Ther 2015; 41: 1281–1287

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

34. Czaja AJ, Nishioka M, Morshed SA, et al. Patterns of nuclear immunofluorescence and reactivities to recombinant nuclear antigens in autoimmune hepatitis. Gastroenterology 1994; 107: 200–207.

35. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology 2001; 33: 544–553.

36. Ma Y, Thomas MG, Okamoto M, et al. Key residues of a major cytochrome P4502D6 epitope are located on the surface of the molecule. J Immunol 2002; 169: 277–285.

37. Czaja AJ. The role of autoantibodies as diagnostic markers of autoimmune hepatitis. Expert Rev Clin Immunol 2006; 2: 33–48.

38. Czaja AJ, Norman GL. Autoantibodies in the diagnosis and management of liver disease. J Clin Gastroenterol 2003; 37: 315–329.

39. Chretien-Leprince P, Ballot E, Andre C, et al. Diagnostic value of anti-F-actin antibodies in a French multicenter study. Ann N Y Acad Sci 2005; 1050: 266–273.

40. Frenzel C, Herkel J, Lüth S, et al. Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis. Am J Gastroenterol 2006; 101: 2731–2736.

41. Couto CA, Bittencourt PL, Porta G, et al. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis. Hepatology 2014; 59: 592–600.

42. Martinez-Neira R, dos Remedios CG, Mackay IR. An actin-myosin functional assay for analysis of smooth muscle (anti-microfilament) autoantibodies in human plasma. J Immunol Methods 2008; 338: 63–66.

43. Soares A, Cunha R, Rodrigues F, et al. Smooth muscle autoantibodies with F-actin specificity. Autoimmun Rev 2009; 8: 713–716.

44. Chan Y, Tong HQ, Beggs AH, et al. Human skeletal musclespecific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo. Biochem Biophys Res Commun 1998; 248: 134–139.

45. Guéguen P, Dalekos G, Nousbaum JB, et al. Double reactivity against actin and alpha-actinin defines a severe form of autoimmune hepatitis type 1. J Clin Immunol 2006; 26: 495–505.

46. Ballot E, Homberg JC, Johanet C. Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis. J Hepatol 2000; 33: 208–215.

47. 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.

48. Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology 1993; 105: 1522–1528.

49. Efe C, Ozaslan E, Wahlin S, et al. Antibodies to soluble liver antigen in patients with various liver diseases: a multicentre study. Liver Int 2013; 33: 190–196.

50. 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.

51. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000; 355: 1510–1515.

52. Terjung B, Söhne J, Lechtenberg B, et al. p-ANCAs in autoimmune liver disorders recognise human beta-tubulin isotype 5 and cross-react with microbial protein FtsZ. Gut 2010; 59: 808–816.

53. Terjung B, Spengler U, Sauerbruch T, et al. “Atypical p-ANCA” in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterology 2000; 119: 310–322.

54. Roozendaal C, de Jong MA, van den Berg AP, et al. Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver diseases. J Hepatol 2000; 32: 734–741.

55. Czaja AJ, Pfeifer KD, Decker RH et al. Frequency and significance of antibodies to asialoglycoprotein receptor in type 1 autoimmune hepatitis. Dig Dis Sci 1996; 41: 1733–1740.

56. Yoshioka M, Mizuno M, Morisue Y, et al. Anti-asialoglycoprotein receptor autoantibodies, detected by a capture-immunoassay, are associated with autoimmune liver diseases. Acta Med Okayama 2002; 56: 99–105.

57. Johnson PJ, McFarlane IG, McFarlane BM, et al. Autoimmune features in patients with idiopathic chronic active hepatitis who are seronegative for conventional auto-antibodies. J Gastroenterol Hepatol 1990; 5: 244–251.

58. McFarlane IG, Hegarty JE, McSorley CG, et al. Antibodies to liver-specific protein predict outcome of treatment withdrawal in autoimmune chronic active hepatitis. Lancet 1984; 2: 954–956.

59. Roggenbuck D, Mytilinaiou MG, Lapin SV, et al. Asialoglycoprotein receptor (ASGPR): a peculiar target of liverspecific autoimmunity. Auto Immun Highlights 2012; 3: 119–125.

60. Martini E, Abuaf N, Cavalli F, et al. Antibody to liver cytosol (anti-LC1) in patients with autoimmune chronic active hepatitis type 2. Hepatology. 1988; 8: 1662–1666.

61. Abuaf N, Johanet C, Chretien P, et al. Characterization of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. Hepatology 1992; 16: 892–898.

62. Czaja AJ, Shums Z, Norman GL. Nonstandard antibodies as prognostic markers in autoimmune hepatitis. Autoimmunity 2004; 37: 195–201.

63. Renous R, Lapierre P, Djilali-Saiah I, et al. Characterization of the antigenicity of the formiminotransferasecyclodeaminase in type 2 autoimmune hepatitis. Exp Cell Res 2004; 292: 332–341.

64. Béland K, Lapierre P, Marceau G, et al. Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection. J Autoimmun 2004; 22: 159–166.

65. 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.

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

67. Czaja AJ. Performance parameters of the diagnostic scoring systems for autoimmune hepatitis. Hepatology 2008; 48: 1540–1548.

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

69. Lamers MMH, van Oijen MGH, Pronk M, et al. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol 2010; 53: 191–198.

70. EASL Clinical Practice Guidelines: autoimmune hepatitis. J Hepatol 2015; 63: 971–1004.

71. Manns MP, Woynarowski M, Kreisel W, et al. Budesonide inducesremission more effectively than prednisone in a controlledtrial of patients with autoimmune hepatitis. Gastroenterology 2010; 139: 1198–1206.

72. Liberal R, de Boer YS, Andrade RJ, et al. Expert clinical man-agement of autoimmune hepatitis in the real world. Aliment Pharmacol Ther 2017; 45: 723–732.

73. Peiseler M, Liebscher T, Sebode M, et al. Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis. Clin Gastroenterol Hepatol 2018; 16: 260–267.

74. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol 1996; 91: 423–433.

75. Akbari M, Shah S, Velayos FS, et al. Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 15–22.

76. Casanova MJ, Chaparro M, Domènech E, et al. Safety of thiopurines and anti-TNF-alpha drugs during pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol 2013; 108: 433–440.

77. van Gerven NMF, Verwer BJ, Witte BI, et al. Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission. J Hepatol 2013; 58: 141–147.

78. 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.