Focus
FEGATO: AUTOIMMUNITÅ, TRAPIANTO, INFEZIONE
Epatite autoimmune: cinquant’anni e non li dimostra!
GIUSEPPE MAGGIORE, MARCO SCIVERES
Dipartimento di Medicina della Procreazione e dell’Età Evolutiva, Scuola di Specialità in Pediatria, Università di Pisa
Maggio 2002 - pagg. 291 -310
Abstract
Autoimmune hepatitis (AIH) is an uncommon disease occurring mainly in women and characterised
by the morphological changes of interface hepatitis on liver biopsy, hypergammaglobulinemia,
elevated serum aminotransferases, and circulating autoantibodies. AIH is
thought to have a basis in aberrant autoreactivity to hepatocyte antigens in genetically predisposed
individuals. AIH is notably heterogeneous with respect to its clinical expression
and laboratory features and patients may present without obvious clinical evidence of liver
disease or with an acute hepatitis. Corticosteroids alone or in conjunction with azathioprine
are the treatment of choice and result in remission induction in over 90% of patients. Sustained
response to therapy may result in substantial regression of fibrosis even in advanced cases.
Rapid withdrawal of immunosuppression is associated with high risk of disease relapse
in many patients. Alternative strategies in patients who have failed to achieve remission on
“standard therapy” include the use of cyclosporine. Liver transplantation is the treatment of
choice in managing patients with decompensated disease unresponsive to “rescue” medical
treatment.
Suggerite dall'AI
Classificazione MeSH
Bibliografia
Nahrungseiweisse.
Dtsch Gesellsch Verd Stoffw
1950;15:113-9.
2. Mackay IR, Taft LI, Cowling DC. Lupoid hepatis. Lancet 1956;2:1323-6.
3. Odièvre M, Maggiore G, Homberg JC, et al. Seroimmunologic classification of chronic hepatitis in 57 children. Hepatology 1983;3:407- 9.
4. Maggiore G, Bernard O, Homberg JC, et al. Liver disease associated with anti-liver-kidney microsome antibody in children. J Pediatr 1986;108:399-401.
5. Alvarez F, Bernard O, Homberg JC, Kreibich G. Anti-liver-kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum. J Exp Med 1985;161:1231-6.
6. Gregorio GV, Portman B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25: 541-7.
7. Vegnente A, Larcher VF, Mowat AP, et al. Duration of chronic aggressive hepatitis and development of cirrhosis. Arch Dis Child 1984;59: 330-5.
8. Maggiore G, Alvarez F, Bernard O. Autoimmune chronic active hepatitis. In: Buts JP, Sokal E. Management of Digestive and Liver Disorders in Infants and Children. Amsterdam: Elsevier, 1993:567-75.
9. Maggiore G, Bernard O, Hadchouel M, Alagille D. Life saving immunosuppressive treatment in severe autoimmune chronic active hepatitis: a case report. J Pediatr Gastroenterol Nutr 1985;4:655-8.
10. Boberg KM, Aadland E, Jahnsen J, et al. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 1998;33:99-103.
11. Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001;120:1502-17.
12. Homberg JC, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with anti-liver/ kidney microsome antibody type 1: a “second” type of “autoimmune” hepatitis. Hepatology 1987;7:1333-9.
13. Maggiore G, Veber F, Bernard O, et al. Autoimmune hepatitis associated with anti-actin antibodies in children. J Pediatr Gastroenterol Nutr 1993;17: 376-81.
14. Manns M, Gerken G, Kriatsoulis A, et al. Characterization of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987;i:292-4.
15. Obermayer-Straub P, Strassburg C, Manns MP. Autoimmune hepatitis. J Hepatol 2002; 32(suppl)181-97.
16. Maggiore G, Porta G, Bernard O, et al. Autoimmune hepatitis with initial presentation as acute hepatic failure in young children. J Pediatr 1990;116:280-2.
17. Porta G, Da Costa Gayoto LC, Alvarez F. Anti-liver-kidney microsome antibody-positive autoimmune hepatitis presenting as fulminant liver failure. J Pediatr Gastroenterol Nutr 1990;11:138-40.
18. Maggiore G, De Benedetti F, Massa M, et al. Circulating levels of interleukin-6, interleukin- 8 and tumor necrosis factor-α in children with autoimmune hepatitis. J Pediatr Gastroenterol Nutr 1995;20:23-7.
19. Djilali-Saiah I, Oullette P, Caillat-Zucman S, et al. CTLA-4 /CD28 region polymorphism in children from families with autoimmune hepatitis. Hum Immunol 2001;12:1356-62.
20. Czaja AJ. Understanding the pathogenesis of autoimmune hepatitis. Am J Gastroenterol 2001;96:1224-31.
21. Czaja AJ, Donaldson PT. Genetic susceptibility for immune expression and liver cell injury in autoimmune hepatitis. Immunol Rev 2000;174:250-9.
22. Framboin 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; 41:146-50.
23. Dessen A, Lawrence CM, Cupo S, et al. Xray cristal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 1997;7:473-81.
24. Vergani D, Wells L, Larcher VF, et al. Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis. Lancet 1985;ii:294-7.
25. Scully LJ, Toze C, Sengar DPS, Gildstein R. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology 1993;104: 1478-84.
26. Agarwal K, Czaja AJ, Jones DEJ, et al. CTLA-4 gene polymorphism and susceptibility to type 1 autoimmune hepatitis. Hepatology 2000;31:49-53.
27. Cookson S, Constantini PK, Clare M, et al. Frequency and nature of citokyne gene polymorphism in type 1 autoimmune hepatitis. Hepatology 1999;30:851-6.
28. Faubion WA, Gores GJ. Death receptors in liver biology and pathobiology. Hepatology 1999;29:1-4.
29. Vogel A, Strassburg CP, Manns MP. Genetic association of vitamin D receptor polymorphism with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 2002;35: 126-31.
30. Beaune P, Dansette PM, Mansuy D, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cythocrome P-450 that hydroxylate the drug. Proc Natl Acad Sci USA 1987;84:551-5.
31. MacFarlane IG. Autoimmunity and hepatotropic viruses. Semin Liver Dis 1991;11: 223- 33.
32. 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;337:1183-6.
33. Laskus T, Slusarczyk J. Autoimmune chronic active hepatitis developing after acute type B hepatitis. Dig Dis Sci 1989;34:1294-7.
34. Loeper J, Descatoire V, Maurice M, et al. Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies. Gastroenterology 1993;104:203- 16.
35. Muratori L, Parola M, Ripalti A, et al. Liver/ kidney microsomial antibody type 1 targets CYP2D6 on hepatocyte plasma membrane. Gut 2000;46:553-61.
36. McFarlane IG. Lessons about antibodies in autoimmune hepatitis. Lancet 2000;355: 1475-6.
37. Gabbiani G, Ryan GB, Lamelin JP et al. Human smooth muscle autoantibody. Its identification as anti-actin antibody and a study of its binding to “non-muscular” cells. Amer J Pathol 1973;72:473-8.
38. Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and others disorders. Clin Exp Immunol 1973; 15:331-4.
39. Guegen M, Meunier-Rotival M, Bernard O, Alvarez F. Anti-liver kidney microsome antibody recognize a cytochrome P450 from the IID subfamily. J Exp Med 1988;168:801-6.
40. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000;355:1510-5.
41. Hajoui O, Debray D, Martin S, Alvarez F. Auto-antibodies to asialoglycoprotein receptor in sera of children with autoimmune hepatitis. Eur J Pediatr 2000;159:310-3.
42. Sasaki M, Yamauchi K, Tokushige K, et al. Clinical significance of autoantibody to hepatocyte membrane antigen in type 1 autoimmune hepatitis. Am J Gastroenterol 2001;96: 846- 51.
43. Abuaf N, Johanney C, Chretien P, et al. Characterisation of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. Hepatology 1992;16:892-8.
44. Lapierre P, Hajoui O, Homberg JC, Alvarez F. Formiminotransferase cyclodeaminase is an organ specific autoantigen recognized by sera of patients with autoimmune hepatitis. Gastroenterology 1999;116:643-9.
45. 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;8:1662-6.
46. Han S, Tredger M, Gregorio GV, et al. Anti- liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease. Hepatology 1995;21:58-62.
47. Senaldi G, Portmann B, Mowat AP, et al. Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis. Arch Dis Child 1992;7:1447- 53.
48. Alvarez F, et al. International Autoimmune Hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-38.
49. Arasu TS, Wyllie R, Hach TF, Fitzgerald JF. Management of chronic aggressive hepatitis in children and adolescents. J Pediatr 1979; 95:514-22.
50. Maggiore G, Bernard O, Hadchouel M, et al. Treatment of autoimmune chronic active hepatitis in childhood. J Pediatr 1984;104:839- 44.
51. Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmmune hepatitis. N Engl J Med 1995;333:958-63.
52. Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002;35:7-13.
53. Hyams JS, Ballow M, Leichtner AM. Cyclosporin treatment of autoimmune chronic active hepatitis. Gastroenterology 1987;93:890-3.
54. Alvarez F, Ciocca M, Canero-Velasco C, et al. Short term cyclosporine induces remission of autoimmune hepatitis in children. J Hepatol 1999;30:222-7.
55. Debray D, Maggiore G, Girardet JP, et al. Efficacy of cyclosporin A in children with type 2 autoimmune hepatitis. J Pediatr 1999;135: 111-4.
2. Mackay IR, Taft LI, Cowling DC. Lupoid hepatis. Lancet 1956;2:1323-6.
3. Odièvre M, Maggiore G, Homberg JC, et al. Seroimmunologic classification of chronic hepatitis in 57 children. Hepatology 1983;3:407- 9.
4. Maggiore G, Bernard O, Homberg JC, et al. Liver disease associated with anti-liver-kidney microsome antibody in children. J Pediatr 1986;108:399-401.
5. Alvarez F, Bernard O, Homberg JC, Kreibich G. Anti-liver-kidney microsome antibody recognizes a 50,000 molecular weight protein of the endoplasmic reticulum. J Exp Med 1985;161:1231-6.
6. Gregorio GV, Portman B, Reid F, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997; 25: 541-7.
7. Vegnente A, Larcher VF, Mowat AP, et al. Duration of chronic aggressive hepatitis and development of cirrhosis. Arch Dis Child 1984;59: 330-5.
8. Maggiore G, Alvarez F, Bernard O. Autoimmune chronic active hepatitis. In: Buts JP, Sokal E. Management of Digestive and Liver Disorders in Infants and Children. Amsterdam: Elsevier, 1993:567-75.
9. Maggiore G, Bernard O, Hadchouel M, Alagille D. Life saving immunosuppressive treatment in severe autoimmune chronic active hepatitis: a case report. J Pediatr Gastroenterol Nutr 1985;4:655-8.
10. Boberg KM, Aadland E, Jahnsen J, et al. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 1998;33:99-103.
11. Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001;120:1502-17.
12. Homberg JC, Abuaf N, Bernard O, et al. Chronic active hepatitis associated with anti-liver/ kidney microsome antibody type 1: a “second” type of “autoimmune” hepatitis. Hepatology 1987;7:1333-9.
13. Maggiore G, Veber F, Bernard O, et al. Autoimmune hepatitis associated with anti-actin antibodies in children. J Pediatr Gastroenterol Nutr 1993;17: 376-81.
14. Manns M, Gerken G, Kriatsoulis A, et al. Characterization of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987;i:292-4.
15. Obermayer-Straub P, Strassburg C, Manns MP. Autoimmune hepatitis. J Hepatol 2002; 32(suppl)181-97.
16. Maggiore G, Porta G, Bernard O, et al. Autoimmune hepatitis with initial presentation as acute hepatic failure in young children. J Pediatr 1990;116:280-2.
17. Porta G, Da Costa Gayoto LC, Alvarez F. Anti-liver-kidney microsome antibody-positive autoimmune hepatitis presenting as fulminant liver failure. J Pediatr Gastroenterol Nutr 1990;11:138-40.
18. Maggiore G, De Benedetti F, Massa M, et al. Circulating levels of interleukin-6, interleukin- 8 and tumor necrosis factor-α in children with autoimmune hepatitis. J Pediatr Gastroenterol Nutr 1995;20:23-7.
19. Djilali-Saiah I, Oullette P, Caillat-Zucman S, et al. CTLA-4 /CD28 region polymorphism in children from families with autoimmune hepatitis. Hum Immunol 2001;12:1356-62.
20. Czaja AJ. Understanding the pathogenesis of autoimmune hepatitis. Am J Gastroenterol 2001;96:1224-31.
21. Czaja AJ, Donaldson PT. Genetic susceptibility for immune expression and liver cell injury in autoimmune hepatitis. Immunol Rev 2000;174:250-9.
22. Framboin 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; 41:146-50.
23. Dessen A, Lawrence CM, Cupo S, et al. Xray cristal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 1997;7:473-81.
24. Vergani D, Wells L, Larcher VF, et al. Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis. Lancet 1985;ii:294-7.
25. Scully LJ, Toze C, Sengar DPS, Gildstein R. Early-onset autoimmune hepatitis is associated with a C4A gene deletion. Gastroenterology 1993;104: 1478-84.
26. Agarwal K, Czaja AJ, Jones DEJ, et al. CTLA-4 gene polymorphism and susceptibility to type 1 autoimmune hepatitis. Hepatology 2000;31:49-53.
27. Cookson S, Constantini PK, Clare M, et al. Frequency and nature of citokyne gene polymorphism in type 1 autoimmune hepatitis. Hepatology 1999;30:851-6.
28. Faubion WA, Gores GJ. Death receptors in liver biology and pathobiology. Hepatology 1999;29:1-4.
29. Vogel A, Strassburg CP, Manns MP. Genetic association of vitamin D receptor polymorphism with primary biliary cirrhosis and autoimmune hepatitis. Hepatology 2002;35: 126-31.
30. Beaune P, Dansette PM, Mansuy D, et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cythocrome P-450 that hydroxylate the drug. Proc Natl Acad Sci USA 1987;84:551-5.
31. MacFarlane IG. Autoimmunity and hepatotropic viruses. Semin Liver Dis 1991;11: 223- 33.
32. 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;337:1183-6.
33. Laskus T, Slusarczyk J. Autoimmune chronic active hepatitis developing after acute type B hepatitis. Dig Dis Sci 1989;34:1294-7.
34. Loeper J, Descatoire V, Maurice M, et al. Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies. Gastroenterology 1993;104:203- 16.
35. Muratori L, Parola M, Ripalti A, et al. Liver/ kidney microsomial antibody type 1 targets CYP2D6 on hepatocyte plasma membrane. Gut 2000;46:553-61.
36. McFarlane IG. Lessons about antibodies in autoimmune hepatitis. Lancet 2000;355: 1475-6.
37. Gabbiani G, Ryan GB, Lamelin JP et al. Human smooth muscle autoantibody. Its identification as anti-actin antibody and a study of its binding to “non-muscular” cells. Amer J Pathol 1973;72:473-8.
38. Rizzetto M, Swana G, Doniach D. Microsomal antibodies in active chronic hepatitis and others disorders. Clin Exp Immunol 1973; 15:331-4.
39. Guegen M, Meunier-Rotival M, Bernard O, Alvarez F. Anti-liver kidney microsome antibody recognize a cytochrome P450 from the IID subfamily. J Exp Med 1988;168:801-6.
40. Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000;355:1510-5.
41. Hajoui O, Debray D, Martin S, Alvarez F. Auto-antibodies to asialoglycoprotein receptor in sera of children with autoimmune hepatitis. Eur J Pediatr 2000;159:310-3.
42. Sasaki M, Yamauchi K, Tokushige K, et al. Clinical significance of autoantibody to hepatocyte membrane antigen in type 1 autoimmune hepatitis. Am J Gastroenterol 2001;96: 846- 51.
43. Abuaf N, Johanney C, Chretien P, et al. Characterisation of the liver cytosol antigen type 1 reacting with autoantibodies in chronic active hepatitis. Hepatology 1992;16:892-8.
44. Lapierre P, Hajoui O, Homberg JC, Alvarez F. Formiminotransferase cyclodeaminase is an organ specific autoantigen recognized by sera of patients with autoimmune hepatitis. Gastroenterology 1999;116:643-9.
45. 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;8:1662-6.
46. Han S, Tredger M, Gregorio GV, et al. Anti- liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease. Hepatology 1995;21:58-62.
47. Senaldi G, Portmann B, Mowat AP, et al. Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis. Arch Dis Child 1992;7:1447- 53.
48. Alvarez F, et al. International Autoimmune Hepatitis group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-38.
49. Arasu TS, Wyllie R, Hach TF, Fitzgerald JF. Management of chronic aggressive hepatitis in children and adolescents. J Pediatr 1979; 95:514-22.
50. Maggiore G, Bernard O, Hadchouel M, et al. Treatment of autoimmune chronic active hepatitis in childhood. J Pediatr 1984;104:839- 44.
51. Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmmune hepatitis. N Engl J Med 1995;333:958-63.
52. Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002;35:7-13.
53. Hyams JS, Ballow M, Leichtner AM. Cyclosporin treatment of autoimmune chronic active hepatitis. Gastroenterology 1987;93:890-3.
54. Alvarez F, Ciocca M, Canero-Velasco C, et al. Short term cyclosporine induces remission of autoimmune hepatitis in children. J Hepatol 1999;30:222-7.
55. Debray D, Maggiore G, Girardet JP, et al. Efficacy of cyclosporin A in children with type 2 autoimmune hepatitis. J Pediatr 1999;135: 111-4.