Skip to main content
SpringerLink
Log in

When and How to Treat the Pediatric Patient

  • Chapter
  • First Online:
Autoimmune Hepatitis

Part of the book series: Clinical Gastroenterology ((CG))

  • 1055 Accesses

Abstract

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disorder affecting mainly females, characterized serologically by high levels of transaminases and immunoglobulin G (IgG), and presence of autoantibodies, and histologically by interface hepatitis, in the absence of a known etiology. AIH responds satisfactorily to immunosuppressive treatment. If left untreated, it progresses rapidly to cirrhosis and liver failure.

The clinical phenotype of AIH in children differs from that of adults. The juvenile form of AIH is subdivided into two types according to the autoantibody profile: type 1, positive for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibody, and/or type 2, positive for anti-liver kidney microsomal antibody type 1 (anti-LKM-1) or anti-liver cytosol type 1 (anti-LC1), autoantibodies rarely described in adult patients. Both AIH types are associated with other autoimmune disorders (about 20%) and a family history of autoimmune disease (40%). Type 2 AIH can be part of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, an autosomal recessive genetic disorder in which the liver disease is reportedly present in some 20% of patients.

The epidemiology of childhood AIH is unknown, but type 1 AIH accounts for two-thirds of the cases and presents usually during adolescence, while type 2 AIH presents at a younger age and also during infancy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mieli-Vergani G, Heller S, Jara P, Vergani D, Chang MH, Fujisawa T, et al. Autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2009;49(2):158–64.

    Article  PubMed  CAS  Google Scholar 

  2. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31(5):929–38.

    Article  PubMed  CAS  Google Scholar 

  3. Pando M, Larriba J, Fernandez GC, Fainboim H, Ciocca M, Ramonet M, et al. Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. Hepatology. 1999;30(6):1374–80.

    Article  PubMed  CAS  Google Scholar 

  4. Homberg JC, Abuaf N, Bernard O, Islam S, Alvarez F, Khalil SH, et al. Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: a second type of “autoimmune” hepatitis. Hepatology. 1987;7(6):1333–9.

    Article  PubMed  CAS  Google Scholar 

  5. Gregorio GV, Portmann B, Reid F, Donaldson PT, Doherty DG, McCartney M, et al. Autoimmune hepatitis in childhood: a 20-year experience. Hepatology. 1997;25(3):541–7.

    Article  PubMed  CAS  Google Scholar 

  6. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. 1990;322(26):1829–36.

    Article  PubMed  CAS  Google Scholar 

  7. Czaja AJ, Bianchi FB, Carpenter HA, Krawitt EL, Lohse AW, Manns MP, et al. Treatment challenges and investigational opportunities in autoimmune hepatitis. Hepatology. 2005;41(1):207–15.

    Article  PubMed  Google Scholar 

  8. Saadah OI, Smith AL, Hardikar W. Long-term outcome of autoimmune hepatitis in children. J Gastroenterol Hepatol. 2001;16(11):1297–302.

    Article  PubMed  CAS  Google Scholar 

  9. Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36(2):479–97.

    Article  PubMed  Google Scholar 

  10. Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, et al. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. Hepatology. 2001;33(3):544–53.

    Article  PubMed  CAS  Google Scholar 

  11. Hennes EM, Zeniya M, Czaja AJ, Pares A, Dalekos GN, Krawitt EL, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48(1):169–76.

    Article  PubMed  Google Scholar 

  12. Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol. 2004;41(4):677–83.

    Article  PubMed  Google Scholar 

  13. Al-Chalabi T, Heneghan MA. Remission in autoimmune hepatitis: what is it, and can it ever be achieved? Am J Gastroenterol. 2007;102(5):1013–5.

    Article  PubMed  Google Scholar 

  14. Ferreira AR, Roquete ML, Toppa NH, de Castro LP, Fagundes ED, Penna FJ. Effect of treatment of hepatic histopathology in children and adolescents with autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2008;46(1):65–70.

    Article  PubMed  Google Scholar 

  15. Sogo T, Fujisawa T, Inui A, Komatsu H, Etani Y, Tajiri H, et al. Intravenous methylprednisolone pulse therapy for children with autoimmune hepatitis. Hepatol Res. 2006;34(3):187–92.

    Article  PubMed  CAS  Google Scholar 

  16. Ustundag G, Kuloglu Z, Kirsaclioglu CT, Kansu A, Erden E, Girgin N. Complete regression of cirrhosis after immunosuppressive treatment in autoimmune hepatitis. Pediatr Int. 2008;50(5):711–3.

    Article  PubMed  Google Scholar 

  17. Kerkar N, Annunziato RA, Foley L, Schmeidler J, Rumbo C, Emre S, et al. Prospective analysis of nonadherence in autoimmune hepatitis: a common problem. J Pediatr Gastroenterol Nutr. 2006;43(5):629–34.

    Article  PubMed  Google Scholar 

  18. Samaroo B, Samyn M, Buchanan C, Mieli-Vergani G. Long-term daily oral treatment with prednisolone in children with autoimmune liver disease does not affect final adult height. Hepatology. 2006;44:438A.

    Google Scholar 

  19. Alvarez F. Autoimmune hepatitis and primary sclerosing cholangitis. Clin Liver Dis. 2006;10(1):89–107.

    Article  PubMed  Google Scholar 

  20. Chang MH, Hadzic D, Rouassant SH, Jonas M, Kohn IJ, Negro F, et al. Acute and chronic hepatitis: working group report of the second World Congress of pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2004;39 Suppl 2:S584–8.

    Article  PubMed  Google Scholar 

  21. Ferreira AR, Roquete ML, Penna FJ, Toppa NH, Castro LP. Type 1 autoimmune hepatitis in children and adolescents: assessment of immunosuppressive treatment withdrawal. J Pediatr (Rio J). 2005;81(4):343–8.

    Google Scholar 

  22. Mieli-Vergani G, Vergani D. Autoimmune hepatitis in children. Clin Liver Dis. 2002;6(3):335–46.

    Google Scholar 

  23. Czaja AJ, Menon KV, Carpenter HA. Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis: a retrospective analysis. Hepatology. 2002;35(4):890–7.

    Article  PubMed  CAS  Google Scholar 

  24. Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354(1):54–66.

    Article  PubMed  CAS  Google Scholar 

  25. Rumbo C, Emerick KM, Emre S, Shneider BL. Azathioprine metabolite measurements in the treatment of autoimmune hepatitis in pediatric patients: a preliminary report. J Pediatr Gastroenterol Nutr. 2002;35(3):391–8.

    Article  PubMed  CAS  Google Scholar 

  26. Dumortier J, Arita CT, Rivet C, LeGall C, Bouvier R, Fabien N, et al. Long-term treatment reduction and steroids withdrawal in children with autoimmune hepatitis: a single centre experience on 55 children. Eur J Gastroenterol Hepatol. 2009;21(12):1413–8.

    Article  PubMed  Google Scholar 

  27. Banerjee S, Rahhal R, Bishop WP. Azathioprine monotherapy for maintenance of remission in pediatric patients with autoimmune hepatitis. J Pediatr Gastroenterol Nutr. 2006;43(3):353–6.

    Article  PubMed  CAS  Google Scholar 

  28. Alvarez FCM, Canero-Velasco C, et al. Short-term cyclosporine induces a remission of autoimmune hepatitis in children. J Hepatol. 1999;30:222–7.

    Article  PubMed  CAS  Google Scholar 

  29. Cuarterolo M, Ciocca M, Velasco CC, Ramonet M, Gonzalez T, Lopez S, et al. Follow-up of children with autoimmune hepatitis treated with cyclosporine. J Pediatr Gastroenterol Nutr. 2006;43(5):635–9.

    Article  PubMed  CAS  Google Scholar 

  30. Debray D, Maggiore G, Girardet JP, Mallet E, Bernard O. Efficacy of cyclosporin A in children with type 2 autoimmune hepatitis. J Pediatr. 1999;135(1):111–4.

    Article  PubMed  CAS  Google Scholar 

  31. Gao E, Lo D, Cheney R, Kanagawa O, Sprent J. Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature. 1988;336:176–9.

    Article  PubMed  CAS  Google Scholar 

  32. Bucy PB, Yan Xu X, Li J, Huang GQ. Cyclosporin A-induced autoimmune disease in mice. J Immunol. 1993;151:1039–50.

    PubMed  CAS  Google Scholar 

  33. Wu DY, Goldschneider I. Cyclosporin A-induced autologous graft-versus-host disease: a prototypical model of autoimmunity and active (dominant) tolerance coordinately induced by recent thymic emigrants. J Immunol. 1999;162(11):6926–33.

    PubMed  CAS  Google Scholar 

  34. Damoiseaux JG, van Breda Vriesman PJ. Cyclosporin A-induced autoimmunity: the result of defective de novo T- cell development. Folia Biol. 1998;44(1):1–9.

    CAS  Google Scholar 

  35. Mieli-Vergani G, Vergani D. De novo autoimmune hepatitis after liver transplantation. J Hepatol. 2004;40(1):3–7.

    Article  PubMed  Google Scholar 

  36. Aw MM, Dhawan A, Samyn M, Bargiota A, Mieli-Vergani G. Mycophenolate mofetil as rescue treatment for autoimmune liver disease in children: a five-year follow-up. J Hepatol. 2009;51:156–60.

    Article  PubMed  CAS  Google Scholar 

  37. Mitchell SA, Bansi DS, Hunt N, Von Bergmann K, Fleming KA, Chapman RW. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology. 2001;121(4):900–7.

    Article  PubMed  CAS  Google Scholar 

  38. Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009;50(3):808–14.

    Article  PubMed  CAS  Google Scholar 

  39. Gregorio GV, McFarlane B, Bracken P, Vergani D, Mieli-Vergani G. Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease. Autoimmunity. 2002;35(8):515–9.

    Article  PubMed  CAS  Google Scholar 

  40. Heneghan MA, Norris SM, O’Grady JG, Harrison PM, McFarlane IG. Management and outcome of pregnancy in autoimmune hepatitis. Gut. 2001;48(1):97–102.

    Article  PubMed  CAS  Google Scholar 

  41. Candia L, Marquez J, Espinoza LR. Autoimmune hepatitis and pregnancy: a rheumatologist’s dilemma. Semin Arthritis Rheum. 2005;35(1):49–56.

    Article  PubMed  Google Scholar 

  42. Terrabuio DR, Abrantes-Lemos CP, Carrilho FJ, Cancado EL. Follow-up of pregnant women with autoimmune hepatitis: the disease behavior along with maternal and fetal outcomes. J Clin Gastroenterol. 2009;43(4):350–6.

    Article  PubMed  Google Scholar 

  43. Duclos-Vallee JC, Sebagh M, Rifai K, Johanet C, Ballot E, Guettier C, et al. A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence. Gut. 2003;52(6):893–7.

    Article  PubMed  Google Scholar 

  44. Kerkar N, Hadzic N, Davies ET, Portmann B, Donaldson PT, Rela M, et al. De-novo autoimmune hepatitis after liver transplantation. Lancet. 1998;351(9100):409–13.

    Article  PubMed  CAS  Google Scholar 

  45. Kerkar N, Dugan C, Rumbo C, Morotti RA, Gondolesi G, Shneider BL, et al. Rapamycin successfully treats post-transplant autoimmune hepatitis. Am J Transplant. 2005;5(5):1085–9.

    Article  PubMed  Google Scholar 

  46. Lobo-Yeo A, Alviggi L, Mieli-Vergani G, Portmann B, Mowat AP, Vergani D. Preferential activation of helper/inducer T lymphocytes in autoimmune chronic active hepatitis. Clin Exp Immunol. 1987;67(1):95–104.

    PubMed  CAS  Google Scholar 

  47. Longhi MS, Hussain MJ, Mitry RR, Arora SK, Mieli-Vergani G, Vergani D, et al. Functional study of CD4  +  CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol. 2006;176(7):4484–91.

    PubMed  CAS  Google Scholar 

  48. Longhi MS, Ma Y, Bogdanos DP, Cheeseman P, Mieli-Vergani G, Vergani D. Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol. 2004;41(1):31–7.

    Article  PubMed  CAS  Google Scholar 

  49. Longhi MS, Ma Y, Mitry RR, Bogdanos DP, Heneghan M, Cheeseman P, et al. Effect of CD4+ CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis. J Autoimmun. 2005;25(1):63–71.

    Article  PubMed  CAS  Google Scholar 

  50. Longhi MS, Meda F, Wang P, Samyn M, Mieli-Vergani G, Vergani D, et al. Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis. Hepatology. 2008;47(2):581–91.

    Article  PubMed  CAS  Google Scholar 

  51. Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Aetiopathogenesis of autoimmune hepatitis. J Autoimmun. 2010;34(1):7–14.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, London, SE5 9RS, UK

    Giorgina Mieli-Vergani (Alex Mowat Professor of Paediatric Hepatology) & Diego Vergani

  2. Paediatric Liver Centre, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK

    Giorgina Mieli-Vergani (Alex Mowat Professor of Paediatric Hepatology)

Authors
  1. Giorgina Mieli-Vergani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diego Vergani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giorgina Mieli-Vergani .

Editor information

Editors and Affiliations

  1. Toronto Western Hospital Liver Centre, Department of Medicine, University of Toronto, Bathhurst St. 399, Toronto, M5T 2S8, Ontario, Canada

    Gideon M. Hirschfield

  2. Toronto Western Hospital Liver Centre, University of Toronto, Bathhurst St. 399, Toronto, M5T 2S8, Ontario, Canada

    E. Jenny Heathcote

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Mieli-Vergani, G., Vergani, D. (2012). When and How to Treat the Pediatric Patient. In: Hirschfield, G., Heathcote, E. (eds) Autoimmune Hepatitis. Clinical Gastroenterology. Springer, New York, NY. https://doi.org/10.1007/978-1-60761-569-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-569-9_7

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-60761-568-2

  • Online ISBN: 978-1-60761-569-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation