Improvement of the histopathology on a maintenance regimen in children with autoimmune hepatitis.

Yıl 2011, Cilt: 16 Sayı: 3, 178 - 187, 22.01.2013

El-sayed İ. Salama Nermine A. Ehsan Behairy E. Behairy Mohsen H. Hussein Menan E. Salem

Öz

Abstract. Autoimmune hepatitis (AIH) is a chronic liver disease characterized histologically by interface hepatitis and fibrosis.   Recent studies have reported that hepatic fibrosis and cirrhosis may be reversible by treatment in some patients.  Combined low dose prednisolone and azathioprine regimen was rarely studied in children with AIH. Twenty children with median age 8±3.5 yrs (9 girls, 11 boys), 18 AIH type I and two were AIH type II, who were in clinical and biochemical remission for at least 6 months, and who had a diagnostic and a follow-up liver biopsy, were included in this study. Different histological stains  were used for assessing the grade of necroinflammatory activity (HAI) and for evaluating the stage of fibrosis according to Ishak scoring system.  Morphometric analysis using LeicaQ500IS image analyzer was applied on Perl's stained liver sections to assess the percentage of liver fibrosis.  Data revealed significant decrease in the median HAI from 8.85 to 3.6 (p=0.001). The median fibrosis score showed significant reduction from 3.9 to 2.4 (p=0.001) and the median fibrosis percentage decreased from 28.7 to 12.8 (p=0.001).   These data provide evidence for regression of fibrosis in AIH in children who responded to the combined low dose immunosuppressive prednisolone and azothioprine regimen. 

Key words: Autoimmune hepatitis, low dose prednisolone combined regimen, fibrosis regression, children

Anahtar Kelimeler

Autoimmune hepatitis, low dose prednisolone combined regimen, fibrosis regression, children

Kaynakça

• 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.
• Dalekos GN, Zachou K, Liaskos C, Gatselis N. Autoantibodies and defined target autoantigens in autoimmune hepatitis: an overview. Eur J Intern Med 2002; 13: 293-303.
• Sciveres M, Caprai S, Palla G, Ughi C, Maggiore G. Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents. Aliment Pharmacol Ther 2004; 19: 209-217.
• Mieli-Vergani G, Vergani D. Autoimmune paediatric liver disease. World J Gastroenterol 2008; 14: 3360-3367.
• Fujisawa T, Sogo T, Komatsu H, Inui A. Autoimmune hepatitis in childhood. Hepatol Res 2007; 37: 496-500.
• Krawitt EL. Autoimmune hepatitis. N Engl J Med 2006; 354: 54-66.
• Mackay IR, Leskovsek NV, Rose NR. Cell damage and autoimmunity: a critical appraisal. J Autoimmun 2008; 30: 5-11.
• Vergani D, Choudhuri K, Bogdanos DP, Mieli- Vergani G. Pathogenesis of autoimmune hepatitis. Clin Liver Dis 2002; 6: 727-737.
• Czaja AJ, Bianchi FB, Carpenter HA, et al. Treatment challenges and investigational opportunities in autoimmune hepatitis. Hepatol 2005; 41: 207-215.
• Parsons CJ, Takashima M, Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol 2007; 22: 79-84.
• Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008; 371: 838-851.
• Dufour JF, DeLellis R, Kaplan MM. Reversibility of hepatic fibrosis in autoimmune hepatitis. Ann Intern Med 1997; 127: 981-985.
• Czaja AJ, Carpenter HA. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis. J Hepatol 2004; 40: 646-652.
• Marcellini M, Di Ciommo V, Callea F, et al. Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric patients: a single- hospital, 10-year follow-up study. J Lab Clin Med 2005; 146: 44.
• George DK, Ramm GA, Powell LW et al. Evidence for altered hepatic matrix degradation in genetic haemochromatosis. Gut 1998; 42: 715-720.
• Kweon Y, Goodman Z, Dienstag J. Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis. Br J Hepatol 2001; 35: 749- 755.
• Poynard T, McHutchison J, Manns M, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002; 122: 1303-1313.
• Kaplan MM, DeLellis RA, Wolfe HJ. Sustained biochemical and histologic remission of primary biliary cirrhosis in response to medical treatment. Ann Intern Med 1997; 126: 682-688.
• Czaja A, Bianchi F, Carpenter H, et al. Treatment challenges and investigational opportunities in autoimmune hepatitis. Hepatology 2005; 41: 207- 215.
• Imanieh MH, Khatami G, Ghavanini AA. Comparison of prednisolone alone and in compination with azathioprine regimens in treatment of autoimmune hepatitis: a prospective study. Irn J Med Sci 2000; 25: 67-71.
• Heneghan MA, McFarlane IG. Current and novel immunosuppressive therapy for autoimmune hepatitis. Hepatology 2002; 35: 7-13.
• Marion AW. Autoimmune hepatitis in children. Clin liver Dis 2005; 335-346.
• Banerjee S, Rahhal R, Bishop WP. Azathioprine monotherapy for maintenance of remission in pediatric patients with autoimmune hepatitis. J Pediatr Gastroenterol Nutr 2007; 45: 490.
• Luxon BA. Autoimmune hepatitis. Making sense of all those antibodies. Postgrad Med 2003; 114: 79-82.
• Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-699.
• Calvaruso V, Burroughs A, Standish R, et al. Computer-assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient. Hepatol 2008; 44: 358- 364.
• Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol 2004; 40: 860-867.
• Friedman SL, Bansal MB. Reversal of hepatic fibrosis fact or fantasy? Hepatology 2006; 43: 82- 88.
• Ferreira AR, Roquete MLV, Topa NH, et al. Effect of treatment of hepatic histopathology in children and adolescents with autoimmune hepatitis. J of Pediatric Gastroenterol Nut 2008; 46: 65-70.
• 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.
• Czaja AJ, Carpenter HA. Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis. Liver Int 2003; 23: 116-132.
• Grİnbaek K, Christensen PB, Hamilton-Dutoit S, et al. Interobserver variation in interpretation of serial liver biopsies from patients with chronic hepatitis C. J Viral Hepat 2002; 9: 443-449.