Historical reflections on autoimmune hepatitis

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 predisolone 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.

Figure 1

Montage and legend as prepared by Dr. Adrian Reuben for “Landmarks in Hepatology”[3]. A: Jan Gösta Waldenström (right) with Dr Göran Bauer, President of the Swedish College of Physicians, Stockholm, c.1989 (courtesy of Dr. Frank Wollheim); B: Henry George Kunkel, Paris, 1979, being informed of his naming for the Lita Annenberg Hazxen Award (courtesy of Dr. Eng M Tan); C: Ian Reay Mackay, on the occasion of his Retirement Symposium in 1987 organized by the Walter and Eliza Hall Institute (courtesy of the subject). Reproduced by courtesy of Dr. Reuben and Wiley and Sons Inc., publishers of Hepatology).

Figure 2

Combined Figures 1 and 2 from a publication[35] on long-term prospective controlled trial of corticosteroid treatment of patients with active chronic (autoimmune) hepatitis. The graphs show duration of treatment and survival for (A), left, non-treated control group and (B), right, corticosteroid treated group, and length of time (months) that the individual patients in either group had been in the investigation at the time of assessment. Numbers indicate the sequence of entry to the trial; +, time of death. Survival was 19/22 for the treated group and 12/27 for the control group. Reproduced with permission of Oxford University Press, publishers of Quarterly Journal of Medicine.