Topic Highlight
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 7, 2008; 14(21): 3292-3300
Published online Jun 7, 2008. doi: 10.3748/wjg.14.3292
Historical reflections on autoimmune hepatitis
Ian R Mackay
Ian R Mackay, Department of Biochemistry & Molecular Biology, Monash University, Clayton Victoria 3800, Australia
Correspondence to: Ian R Mackay, MD, Department of Biochemistry & Molecular Biology, Monash University, Clayton Victoria 3800, Australia. ian.mackay@med.monash.edu.au
Telephone: +61-3-99051437
Fax: +61-3-96822751
Received: January 3, 2008
Revised: February 29, 2008
Accepted: March 7, 2008
Published online: June 7, 2008
Abstract

Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Young women featured prominently in early descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with prednisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the “ancestral” B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases.

Keywords: Medical history; Autoimmune hepatitis; Lupoid hepatitis; Liver disease autoantibodies; Immunosuppressive therapy; HLA-disease associations