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A 50-year experience with autoimmune hepatitis: and where are we now?

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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.

Early observations

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.

Recent advances

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.

Future prospects

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.

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Acknowledgments

This review is based on Special Remarks delivered at the 2nd International Forum of the 96th Annual Meeting of the Japanese Society of Gastroenterology, and subsequent seminars hosted by Professor M. Zeniya, Jikei University, Tokyo, and Professor Katsuhide Yamamoto, Okayama University, Okayama. Warm thanks are extended to Professor Hiromi Ishibashi for facilitation arrangements and critical reading of the manuscript.

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  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia

    Ian R. Mackay

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Mackay, I.R. A 50-year experience with autoimmune hepatitis: and where are we now?. J Gastroenterol 46 (Suppl 1), 17–28 (2011). https://doi.org/10.1007/s00535-010-0325-2

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