Epigenetic considerations and the clinical reevaluation of the overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis

J Autoimmun. 2013 Mar:41:140-5. doi: 10.1016/j.jaut.2012.10.004. Epub 2012 Nov 25.

Abstract

Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndromes, we evaluated a large series of consecutive patients with PBC (n = 565) and AIH (n = 196) to identify a group of patients with corticosteroid-responsive PBC-AIH overlap syndrome. Within this series, a total of 490 patients were biopsied based upon staging or diagnostic needs. Review of the biopsies in conjunction with the International AIH Group criteria identified 80 patients with suspected overlap syndrome and 52 patients agreed to participate in the study and were prospectively treated with corticosteroids. Of these, 40/52 (77%) achieved a complete biochemical response (i.e. normal ALT, AST, and IgG) within 12 months of treatment. A survey of pre-treatment characteristics of the 40 responders revealed more severe interface hepatitis. Serum IgG levels ≥1.3x the upper limit of normal had 60% sensitivity and 97% specificity rates for steroid-responsiveness while the use of a higher threshold (≥2.0x) reduced sensitivity to 10%. When the Paris criteria for PBC-AIH were applied to the steroid-responsive patients, 29/40 (73%) cases fulfilled at least two of the three Paris criteria. Applying the recently designed simplified IAIHG scoring system, 35/40 (88%) had a "definite" diagnosis of AIH. This study supports the hypothesis that a complete response to corticosteroids may denote a variant of a PBC-AIH overlap syndrome which could be identified prior to treatment by modified Paris criteria in concert with the simplified IAIHG scoring system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Azathioprine / therapeutic use
  • Drug Therapy, Combination
  • Epigenesis, Genetic*
  • Female
  • Hepatitis, Autoimmune / drug therapy*
  • Hepatitis, Autoimmune / genetics
  • Hepatitis, Autoimmune / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Liver Cirrhosis, Biliary / drug therapy*
  • Liver Cirrhosis, Biliary / genetics
  • Liver Cirrhosis, Biliary / immunology
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Prospective Studies
  • Syndrome
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Autoantibodies
  • Immunoglobulin G
  • Prednisolone
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Azathioprine