medigraphic.com
Órgano Oficial de la Asociación Mexicana de Infectología Pediátrica y la SLIPE.

2008, Number 86

<< Back Next >>

Rev Enfer Infec Pediatr 2008; 21.22 (86)

Treatment of hepatitis autoinmune in children and adolescents: qualitative analysis of evidence

Díaz MS, Montijo BE, Cervantes BR, Zárate MF, Mora MI, Bacarreza ND, Ramírez MJ

Language: Spanish
References: 50
Page: 48-55
PDF size: 209.16 Kb.


ABSTRACT

Background: Corticosteroids and azathioprine are considered first-line drugs in the treatment of autoimmune hepatitis. However, new treatments have recently been tested for those patients who do not respond, who develop tolerance or toxicity to these agents.
Objective: To evaluate the effectiveness of the different types of immunosuppressive drugs and their role in the treatment of autoimmune hepatitis in children and adolescents. To perform an evidence-based analysis on the treatment of children with autoimmune hepatitis treated with immunosuppressants.
Methods: An exhaustive review of the literature was made in Medline, PubMed, EMBASE, DARE, Clinical Trials Registered, Bandolier, Ovid, Science-Direct, EBSCO, LILACS, Artemisa and IMBIOMED databases. We searched for all the articles about the treatment with immunosuppressants for autoimmune hepatitis in children and adolescents. Results are presented in tables and data were analyzed qualitatively.
Results: Steroids (prednisone and prednisolone) and azathioprine are the only drugs that have been used in controlled clinical trials in pediatric population. Results from these studies show that steroids alone can induce remission. However, when used in combination with azathioprine, toxicity and tolerance are improved. Cyclosporine is a promising drug that has been used in a large series (openlabel studies) of children with good results in the short term. No controlled trials have tested this agent. There is no evidence regarding the use of other immunosuppressive drugs for the treatment of autoimmune hepatitis in children and adolescents.
Conclusion: Steroids and azathioprine are still the mainstay of treatment for autoimmune hepatitis in children and adolescents. Combined therapy should be considered from the beginning since it is better tolerated and adverse effects are lower. Evidence suggests that cyclosporine could be used in case of treatment failure. There is no supportive evidence regarding the use of other immunosuppressants in treating this disease. Controlled clinical trials are further necessary to evaluate the role of other agents in pediatric population.


REFERENCES

  1. Terminology of chronic hepatitis. International Working Party Report. Am J Gastroenterol 1995;90(2):181-9.

  2. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs K, et al. International Hepatitis Group Report: review of criteria for diagnosis of autoimmunehepatitis. J Hepatol 1999;31:929-38.

  3. Heneghan MA, Mc Farlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002;35(1):7-13.

  4. Saadah OI, Smith AL, Hardikar W. Long-term outcome of autoimmune hepatitis in children. J Gastroenterol Hepatol 2001;16:1297-302.

  5. Czaja AJ. Treatment strategies in autoimmune hepatitis. Clin Liver Dis 2002;6(3):799-824.

  6. Imanieh MH, Khatamani G, Ghavanini AA. Comparison of prednisolone, alone or in combination with azathioprine regimens in treatment of autoimmune hepatitis: a prospective study. Iran J Med Sci 2000;25(1-2):67-71.

  7. Arasu TS, Wyllie R, Hatch TF, Fitzgerald JF. Management of chronic aggressive hepatitis in children and adolescents. J Pediatr 1979;95(4):514-22.

  8. Maggiore G, Bernard O, Hadchouel M, Hadchouel P, Odievre M, Alagille D. Treatment of autoimmune chronic active hepatitis in childhood. J Pediatr 1984;104(6):839-44.

  9. Soloway RD, Summerskill WHJ, Baggenstoss AH, Geall MG, Gitnick GL, et al. Clinical, biochemical and hystological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology 1972;63(5):820-33.

  10. Takenami T, Sakaguchi K, Nishimura M, Miyake Y, Miyashita M, et al. Therapeutic effects of azathioprine in combination with low dose prednisolone in patients with intractable autoimmune hepatitis type 1. Acta Med Okayama 2001;55(6):341-7.

  11. Murray-Lyon IM, Stern RB, Williams R. Controlled trial of prednisone and azathioprine in active chronic hepatitis. Lancet 1973;1:735-7.

  12. Cook GC, Mulligan R, Sherlock S. Controlled prospective trial of corticosteriod therapy in active chronic hepatitis. QJ Med 1971;40:155-85.

  13. Mistilis SP, Blackburn CRB. The treatment of chronic active hepatitis with 6-mercaptopurine and azathioprine. Australas Ann Med 1967;16:305-11.

  14. Pratt DS, Flavin DP, Kaplan MM. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine. Gastroenterology 1996;110:271-4.

  15. Page AR, Condie RM, Good RA. Suppression of plasma cell hepatitis with 6-mercaptopurine. Am J Med 1964;36:200-13.

  16. De Boer NKH, van Nieuwkerk CMJ, Aparicio-Pages MN, de Boer SY, Derijks LJJ, et al. Promissing treatment of autoimmune hepatitis with 6-thioguanine after adverse events on azathioprine. Eur J Gastroenterol Hepatol 2005;17(4):457-61.

  17. Weigand J, Schüller A, Kanzler S, Lohse A, Beuers U, et al. Budesonide in previously untreated autoimmune hepatitis. Liv Int 2005;25:927-34.

  18. Czaja AJ, Lindor KD. Failure of budesonide in a pilot study of treatment dependent autoimmune hepatitis. Gastroenterology 2000;119:1312-6.

  19. Audegay P, Signoret C. Hépatite autoimmune: interêt du budesonide en cas d´intolerance à la prednisolone. Presse Medicale 1999;28(4):176.

  20. Danielsson A, Prytz H. Oral budesonide for treatment of autoimmune chronic active hepatitis. Aliment Pharmacol Ther 1994;8:585-90.

  21. Csespregi A, Röcken C, Treiber T, Malfertheiner P. Budesonide induces complete remission in autoimmune hepatitis. World J Gastroenterol 2006;12(9):1362-6.

  22. Rebollo Bernández J, Cifuentes-Mimoso C, Piñar-Moreno A, Caunedo Alvarez A, Salas-Herrero E, et al. Deflazacort for long term maintenance of remission in type 1 autoimmune hepatitis. Rev Esp Enferm Dig 1999;91:630-8.

  23. Bae SH, Kim JS, Kim DH. Deflazacort for type 1 autoimmune hepatitis in a korean girl. J Korean Med Sci 2006;21:758-60.

  24. Alvarez F, Ciocca M, Cañero-Velasco C, Ramonet M, de Davila MTG, et al. Short-term cyclosporine induces a remission in children. J Hepatol 1999;30:222-7.

  25. Debray D, Maggiore G, Girardet JP. Efficacy of cyclosporine in chidren with type 2 autoimmune hepatitis. J Pediatr 1999;135(1):111-4.

  26. Malekzadeh R, Nasseri-Moghaddam S, Kaviani MJ, Taheri H, Kamalian N, et al. Cyclosporine A is a promising alternative to corticosteroids in autoimmune hepatitis. Dig Dis Sci 2001;46:1321-7.

  27. Sciveres M, Capral S, Palla G Ughi C, Maggiore G. Effectiveness and safety of cyclosporine as therapy for autoimmune diseases of the liver in children and adolescents. Aliment Pharmacol Ther 2004;19:209-17.

  28. Hyams JS, Ballow M, Leitchner AM. Cyclosporine treatment of autoimmune chronic active hepatitis. Gastroenterology 1987;93:890-3.

  29. Sherman KE, Narkewicz M, Pinto PC. Cyclosporine in the management of corticosteroid-resistant type 1 autoimmune chronic active hepatitis. J Hepatol 1994;21:1040-7.

  30. Debray D, Maggiore G, Bernard O. Cyclosporine treatment of autoimmune hepatitis in children. J Pediatr Gastroenterol Nut 1995;20:470.

  31. Jackson LD, Song E. Cyclosporine in the treatment of corticosteroid resistant autoimmune hepatitis. Gut 1995;36:459-61.

  32. Senturk H. Treatment of corticosteroid-azathioprine resistant autoimmune hepatitis with cyclosporin A. Indian J Gastroenterol 1995;14(3):110-1.

  33. Launay V, Gottrand F, Michaud L, Masy E, Turck D, Farriaux JP. Traitement par la ciclosporine d´une hépatite auto-immune révélée pau une insuffisance hépatocellulaire aiguë. Arch Pediatr 1997;4:40-3.

  34. Fernandes NF, Redeker AG, Vierling JM, Villamil FG, Fong TL. Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis. Am J Gastroenterol 1999;94(1):241-8.

  35. Ben Halima N, Chaabouni M, Karray A, Krichen A, Masmoudi H, et al. Ciclosporine a dans le traitement de l´hépatite auto-immune de l´enfant: à propos de 1 cas. Tunis Medical 2002;80(9):565-9.

  36. Perreaux F, Zentay D, Capron F, Trioche P, Odievre M, et al. Azathioprine-induced lung toxicity and efficacy of cyclosporine A in a young girl with type 2 autoimmune hepatitis. J Ped Gastroenterol Nut 2000;31:190-2.

  37. Richardson PD, James PD, Ryder SD. Mycophenolate mofetil for maintenance of remission in autoimmune hepatitis in patients resistant to or intolerant of azathioprine. J Hepatol 2000;33:371-5.

  38. Brunt EM, di Bisgeglie AM. Hystologycal changes after the use of mycophenolate mophetil in autoimmune hepatitis. Hum Pathol 2004;35(4):509-12.

  39. Devlin SM, Swain MG, Urbanski SJ Buraj KW. Mycophenolate Mophetil for the treatment of autoimmune hepatitis in patients refractory to standard therapy. Can J Gastroenterol 2004;18:321-5.

  40. Schuppan D, Herold C, Strobel D, Schneider HT, Hahn EG. Successful treatment of therapy-refractory autoimmune hepatitis with mycophenolate mophetil. Hepatology 1998;28:A1960.

  41. Chatur N, Ramji A, Bain BG, Ma MM, Marotta PJ, et al. Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian Association for the study of liver (CASL) experience mycophenolate mophetil and tacrolimus. Liv Int 2005;25:723-7.

  42. Aquel BA, Machicao V, Rosser B, Salyanarayana R, Harnois DM, et al. Efficacy of tacrolimus in the treatment of steroid refractory autoimmune hepatitis. J Clin Gastroenterol 2004;38(9):805-9.

  43. Van Thiel DH, Wright H, Carrol P, Abu-Elmagd K, Rodriguez-Rilo H, et al. Tacrolimus a potential new treatment for autoimmune chronic active hepatitis : results of an open label preliminary trial. Am J Gastroenterol 1995;90:771-6.

  44. Heneghan MA, Rizzi P, McFarlane IG, Portmann B, Harrison PM. Low dose tacrolimus as treatment of severe autoimmune hepatitis: potential role in remission induction. Gut 1999;44(Suppl 1):A61.

  45. Burak KW, Urbanski SJ, Swain MG. Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate. J Hepatol 1998;29:990-3.

  46. Venkataramani A, Jones MB, Sorrell MF. Methotrexate therapy for refractory chronic active autoimmune hepatitis. Am J Gastroenterol 2001;96(12):3432-4.

  47. Ortego-Centeno N, Salmeron-Escobar J, Callejas-Rubio JL, Parra-Ruiz J, Benticuaga-Martinez MN. Metotrexato en el tratamiento de la hepatitis autoinmunitaria. Gastroenterol Hepatol 2004;27(5):344.

  48. Kanzler S, Gerken G, Dienes HP, Meyer Zum Büschenfelde KH, Lohse AW. Cyclophosphamide as alternative immunosuppressive therapy for autoimmune hepatitis: report of three cases. Z Gastroeneterol 1997;35:571-8.

  49. Gilmore IT, Cowan RE, Axon ATR, Thompson RHP. Controlled trial of cyclophosphamide in active chronic hepatitis. Br Med J 1979;1(6171):1120-1.

  50. Jadad AR, et al. Assesing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12.




2020     |     www.medigraphic.com