Autoimmune Hepatitis: Surviving Crises of Doubt and Elimination

Abstract

Autoimmune hepatitis (AIH) has survived doubts about its existence [1][2][3][4] and clinical and pathological definitions that have overly restricted its clinical phenotype. 5-10 AIH was originally considered to be a disease predominantly of young women associated with hypergammaglobulinemia 1,6-8 and defined by one or the other of its major pathological configurations ("chronic persistent hepatitis" versus "chronic active hepatitis"). 9,10 AIH has also survived proposals in favor of putative causative agents that have threatened its validity, [11][12][13][14][15][16][17][18] the continuing lack of a signature marker to define its identity, [19][20][21][22] and reduced investigational and funding priorities because of its rarity. 23 The emergence of AIH from its origins as "lupoid hepatitis," 24,25 "chronic active liver disease" (CALD), 26,27 and "hepatitis B surface antigen (HBsAg)-negative chronic active hepatitis" 13,28 has constituted a learning process that has overcome hurdles of preconceptions, misunderstandings, skepticisms, and biases (Fig. 1), and it has exemplified a maturation process that has involved an international cadre of investigators. Ironically, the attempt that was made by an eminent group of European pathologistsnicknamed by Dame Sheila Sherlock "The Gnomes of Zurich" 29 -to codify the confusing nomenclature of

The Discovery of the Hepatitis D Virus: Three Princes of Serendip and the Recognition of Autoantibodies to Liver‐Kidney Microsomes

“…A first clue to the origin of CH came in the 1960s from the association of some cases with a battery of serum autoantibodies to normal human antigens, such as the antinuclear antibody (ANA), anti‐smooth muscle antibody, and others; and the diagnosis came to be known as autoimmune hepatitis (AIH) (see the essay by Albert Czaja, 5 “Autoimmune Hepatitis: Surviving Crises of Doubt and Elimination,” elsewhere in this series). Thus, these antibody‐positive CH cases were autoimmune hepatitides.…”