title: A 50-year experience with autoimmune hepatitis: and where are we now?
abstract: BACKGROUND
  Autoimmune hepatitis (AIH) as chronic active hepatitis became recognized in the 1940s as a progressive hyperglobulinemic disease affecting younger women attributed to persisting virus infection of the liver: autoimmunity then was barely on the horizon.
  The lupus erythematosus (LE) cell reported in 1948 signified the presence of antinuclear autoantibodies, promoting perceptions of autoimmunity in certain chronic diseases. Recognition of LE cells in chronic hepatitis led to the designation of 'lupoid hepatitis', with autoimmunity further substantiated by anti-cytoplasmic autoantibodies detected by complement fixation. Next a serum reactant with smooth muscle of rodent stomach was found to have a wider distribution and became identified as an autoantibody to filamentous (F) actin. Therapy with corticosteroids proved effective, particularly combined with azathioprine. Various trials showed greatly improved survival and established modern therapy of AIH. An HLA-based predisposition (B8, DR3) was the first pointer to a genetic etiology.
  
  
  BACKGROUND
  Recombinant or purified autoantigenic substrates have led to automated assays, which, together with improved immunofluorescence procedures, allow serological confidence in diagnosis and institution of effective immunosuppressive therapies. The liver-kidney 'microsomal' autoantigen reactive with cytochrome P450 2D6 distinguishes two serological types of AIH that appear pathogenetically distinct. Molecular characterization of antigens and epitopes remains wanting in type 1 AIH.
  
  
  CONCLUSIONS
  The challenge remains with both types of AIH to elucidate in molecular terms the genetic and environmental basis of pathogenesis from initiation to ultimate progression and cirrhosis (when inadequately treated). Advancing technologies are bringing this goal closer to being attainable.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. ian.mackay@monash.edu
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackay
mesh_terms: D000367:Age Factors; D000974:Antibodies, Antinuclear / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000627:therapeutic use; D006680:HLA Antigens / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D012737:Sex Factors
chemical_list: D000974:Antibodies, Antinuclear; D005938:Glucocorticoids; D006680:HLA Antigens; D007166:Immunosuppressive Agents