Autoimmune Hepatitis: From the Clinic to the Diagnostics Laboratory

Autoimmune hepatitis (AIH), formerly known as chronic active hepatitis (CAH), first attracted attention around 1948. It probably existed as “subacute hepatitis” before that time, however. 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 then seemed to be a persistently active virus in the liver. Various anti-tissue antibodies became recognized during 1955 to 1965, detected first to nuclear antigens by the lupus erythematosus (LE) cell test and immunofluorescence (IFL) for antinuclear autoantibody, then to a smooth muscle antigen with the true reactant later identified as the microfilament F actin, and then to an antigen enriched in endoplasmic reticulum (microsomes) of liver and kidney cells. The availability of recombinant or finely purified autoantigen now allows for automated molecular assays for some of these reactivities and this, with improved IFL 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, AIH. Autoimmune hepatitis has been a controversial subject since being named as such in 1965,[6][1] with eventual international endorsement in 1993.[7][2] Hence, relevant historical material is included. * AIH : autoimmune hepatitis CAH : chronic active hepatitis LE : lupus erythematosus SLE : systemic lupus erythematosus ANA : anti-nuclear autoantibodies IFL : immunofluorescence SMA : smooth muscle antibody LKM : liver and kidney microsomes HBV : hepatitis B virus HCV : hepatitis C virus IAIHG : International Autoimmune Hepatitis Group PBC : primary biliary cirrhosis CHC : chronic hepatitis C UNL : upper normal limit Ig : immunoglobulin IgG : immunoglobulin G SLA/LP : soluble liver antigen and liver pancreas LC-1 : liver cytosol antigen type 1 IUIS : International Union of Immunological Societies ds : double-stranded ss : single-stranded ANCA : anti-neutrophil cytoplasmic antibody cANCA : cytoplasmic anti-neutrophil cytoplasmic antibody pANCA : perinuclear anti-neutrophil cytoplasmic antibody pANNA : peripheral anti-neutrophil nuclear antibody ELISA; : enzyme-linked immunosorbent assay G : globular F : filamentous LP : liver-pancreas antigen SLA : soluble liver antigen tRAP; : tRNA-associated protein SHMT : serine hydroxymethyl transferases UGT : uridine diphosphate glucuronosyl transferases APECED : autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy APS-1 : autoimmune polyendocrine type 1 FTCD : formiminotransferase cyclodeaminase LSP : liver-specific lipoprotein ASGPR : asialoglycoprotein receptor PSC : primary sclerosing cholangitis AIRE : autoimmune regulator RLN : regional lymph node [1]: #ref-6 [2]: #ref-7