Autoimmune hepatitis: From the clinic to the diagnostics laboratory

Autoimmune hepatitis, formerly called chronic hepatitis, first attracted attention around 1948, although existing unrecognized well before that. At that time, young women were mainly affected and the outlook was poor. Suspicions of an immunological abnormality in CAH were raised by extreme hypergammaglobulinemia, but the likely primary culprit seemed to be a persistingly active virus in the liver. Various anti-tissue antibodies became recognized in the 1955-65 decade, first to nuclear antigens (L.E. cell test, immunofluorescence for ANA), then to smooth muscle (SMA) with the true reactant identified as the microfilament F actin, and then to a a??microsomala?? antigen enriched in endoplasmic reticulum of liver and kidney cells (LKM). Presently, the availability of recombinant or finely purified autoantigen allows for automated molecular assays for some of these reactivities and this, with improved immunofluorescence technologies, has led to serological confidence in diagnosis with institution of highly effective suppressive therapies. Meanwhile immunologists remain sorely challenged in their attempts to define the pathogenetic steps from initiation, relentless persistence to ultimate hepatocytolytic destruction in this enigmatic liver disorder, autoimmune hepatitis.