Abstract
Autoimmune hepatitis (AIH) remains an enigmatic condition that affects children of all ages. Although much knowledge has emerged over the past four decades regarding autoimmune diseases, the lack of a spontaneous animal model has hindered a more complete understanding of the pathophysiology of AIH. Serum autoimmune markers, combined with biochemical and histologic evidence of hepatocellular injury and absent other diagnostic considerations, are necessary to diagnose AIH. The clinical spectrum ranges from asymptomatic elevation of aminotransferase levels to acute liver failure. Patients with AIH type 1 are more likely to be older and have cirrhosis at the time of diagnosis, whereas those with AIH type 2 may have a more fulminant course and require life-long immunosuppressant medications. Overlap syndromes occur in children but are rare. Treatment with prednisone and azathioprine, alone or in combination, reverses the clinical course and improves biochemical abnormalities. Should liver transplantation be necessary, autoimmune injury may recur in the allograft.
Similar content being viewed by others
References and Recommended Reading
Gregorio GV, Portmann B, Karani J, et al.: Autoimmune hepatitis in childhood: a 20-year experience. Hepatology 1997, 25:541–547. The largest published experience in autoimmune liver disease in children by an international expert in this condition.
Yachha SK, Srivastava A, Chetri K, et al.: Autoimmune liver disease in children. J Gastroenterol Hepatol 2001, 16:674–677.
Johnson PJ, McFarlane IG, Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993, 18:998–1005.
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. An update of the consensus report by international authorities in the diagnosis of AIH in both adults and children.
Davidson A, Diamond B: Autoimmune diseases. N Engl J Med 2001, 345:340–350.
Czaja AJ, Doherty DG, Donaldson PT: Genetic bases of autoimmune hepatitis. Dig Dis Sci 2002, 47:2139–2150. A comprehensive review by international experts in AIH.
Jaeckel E: Animal models of autoimmune hepatitis. Semin Liver Dis 2002, 22:325–338.
Donaldson PT: Genetics in autoimmune hepatitis. Semin Liver Dis 2002, 22:353–364.
Doherty DG, Donaldson PT, Underhill JA, et al.: Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis. Hepatology 1994, 19:609–615.
Donaldson PT, Doherty DG, Hayllar KM, et al.: Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology 1991, 13:701–706.
Agarwal K, Jones DE, Daly AK, et al.: CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis. J Hepatol 2000, 32:538–541.
Finnish-German APECED Consortium: An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. The Finnish-German APECED Consortium. Nat Genet 1997, 17:399–403.
Nagamine K, Peterson P, Scott HS, et al.: Positional cloning of the APECED gene. Nat Genet 1997, 17:393–398.
Goldstein NS, Rosenthal P, Sinatra F, Dehner LP: Liver disease in polyglandular autoimmune disease type one: clinicopathologic study of three patients and review of the literature. Pediatr Pathol Lab Med 1996, 16:625–636.
Obermayer-Straub P, Perheentupa J, Braun S et al.: Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Gastroenterology 2001, 121:668–677.
Mieli-Vergani G, Vergani D: Autoimmune hepatitis. Arch Dis Child 1996, 74:2–5.
Czaja AJ, Norman GL: Autoantibodies in the diagnosis and management of liver disease. J Clin Gastroenterol 2003, 37:315–329. A comprehensive review of the autoantibodies used to establish the diagnosis of autoimmune liver disease.
Clifford BD, Donahue D, Smith L, et al.: High prevalence of serological markers of autoimmunity in patients with chronic hepatitis C. Hepatology 1995, 21:613–619.
Gough A, Chapman S, Wagstaff K, et al.: Minocycline induced autoimmune hepatitis and systemic lupus erythematosuslike syndrome. BMJ 1996, 312:169–172.
Czaja AJ: Behavior and significance of autoantibodies in type 1 autoimmune hepatitis. J Hepatol 1999, 30:394–401.
Strassburg CP, Manns MP: Autoantibodies and autoantigens in autoimmune hepatitis. Semin Liver Dis 2002, 22:339–352.
Czaja AJ, Shums Z, Norman GL, et al.: Frequency and significance of antibodies to actin in type 1 autoimmune hepatitis. Hepatology 1996, 24:1068–1073.
Lohr H, Manns M, Kyriatsoulis A, et al.: Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibodypositive autoimmune chronic active hepatitis. Clin Exp Immunol 1991, 84:297–302.
Wies I, Brunner S, Henninger J, et al.: Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000, 355:1510–1515.
Czaja AJ, Shums Z, Norman GL: Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis. Autoimmunity 2002, 35:475–483.
Pelli N, Fensom AH, Slade C, et al.: Argininosuccinate lyase: a new autoantigen in liver disease. Clin Exp Immunol 1998, 114:455–461.
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, 116:643–649.
Muratori L, Parola M, Ripalti,A et al.: Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis. Gut 1998, 42:721–726.
Mieli-Vergani G, Vergani D: Autoimmune liver disease. Indian J Pediatr 2002, 69:93–98.
Lohse AW, zum Buschenfelde KH, Franz B, et al.: Characterization of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology 1999, 29:1078–1084.
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.
Poupon R: Autoimmune overlapping syndromes. Clin Liver Dis 2003, 7:865–878.
Gopal S, Nagral A, Mehta S: Autoimmune sclerosing cholangitis: an overlap syndrome in a child. Indian J Gastroenterol 1999, 18:31–32.
Mieli-Vergani G, Vergani D: Autoimmune liver disease in children. Ann Acad Med Singapore 2003, 32:239–243.
Mieli-Vergani G, Vergani D: Autoimmune hepatitis in children. Clin Liver Dis 2002, 6:335–346.
Herzog D, Yamamoto AM, Jara P, et al.: Sera of children with hepatitis C infection and anti-liver-kidney microsome-1 antibodies recognize different CYP2D6 epitopes than adults with LKM+/HCV+ sera. J Pediatr Gastroenterol Nutr 1999, 9:551–555.
Apak RA, Besbas N, Ozdemir S et al.: Hepatitis as the presenting symptom of childhood systemic lupus erythematosus. Turk J Pediatr 1999, 41:541–544.
Chuang E, Ruchelli E, Mulberg AE: Autoimmune liver disease and sickle cell anemia in children: a report of three cases. J Pediatr Hematol Oncol 1997, 19:159–162.
da Silva ME, Porta G, Goldberg AC, et al.: Diabetes mellitusrelated autoantibodies in childhood autoimmune hepatitis. J Pediatr Endocrinol Metab 2002, 15:831–840.
Ertem D, Acar Y, Pehlivanoglu E: Autoimmune complications associated with hepatitis A virus infection in children. Pediatr Infect Dis J 2001, 20:809–811.
Croffy B, Kopelman R, Kaplan M: Hypereosinophilic syndrome: association with chronic active hepatitis. Dig Dis Sci 1988, 33:233–239.
Arvola T, Mustalahti K, Saha MT, et al.: Celiac disease, thyrotoxicosis, and autoimmune hepatitis in a child. J Pediatr Gastroenterol Nutr 2002, 35:90–92.
Andries S, Casamayou L, Sempoux C, et al.: Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine. Transplantation 2001, 72:267–272.
Bahar RJ, Yanni GS, Martin MG, et al.: Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic hepatitis in children. Transplantation 2001, 72:829–833.
Czaja AJ, Freese DK: Diagnosis and treatment of autoimmune hepatitis. Hepatology 2002, 36:479–497. A comprehensive review authored by an adult and pediatric expert in AIH. This document serves as an AASLD Practice Guideline.
Maggiore G, Bernard O, Hadchouel M, et al.: Treatment of autoimmune chronic active hepatitis in childhood. J Pediatr 1984, 104:839–844.
Alvarez F, Ciocca M, Canero-Velasco C, et al.: Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol 1999, 30:222–227.
Sherman KE, Narkewicz M, Pinto PC: Cyclosporine in the management of corticosteroid-resistant type I autoimmune chronic active hepatitis. J Hepatol 1994, 21:1040–1047.
Medina J, Garcia-Buey L, Moreno-Otero R: Review article: Immunopathogenetic and therapeutic aspects of autoimmune hepatitis. Aliment Pharmacol Ther 2003, 17:1–16.
Smith D, Stringer MD, Wyatt J, et al.: Orthotopic liver transplantation for acute liver failure secondary to autoimmune hepatitis in a child with autoimmune polyglandular syndrome type 1. Pediatr Transplant 2002, 6:166–170.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Squires, R.H. Autoimmune hepatitis in children. Curr Gastroenterol Rep 6, 225–230 (2004). https://doi.org/10.1007/s11894-004-0012-7
Issue Date:
DOI: https://doi.org/10.1007/s11894-004-0012-7