Discrimination of autoimmune hepatitis: autoantibody typing and beyond

For over 20 years autoimmune hepatitis has been classified into types 1 and 2, an autoantibody-based classification that has stood the test of time. In type 1 autoimmune hepatitis, the main circulating autoantibodies, although not specific for the disease, are antinuclear antibodies, smooth-muscle antibodies, and anti F-actin antibodies. Soluble liver antigen antibodies have been found in approximately 10-30% of adult patients with type 1 disease, and are more common in children with type 1 and type 2 autoimmune hepatitis. Atypical p-antineutrophil cytoplasmic autoantibodies frequently occur in type 1 autoimmune hepatitis but are non-specific. Antimitochondrial antibodies, although more specific and sensitive for primary biliary cirrhosis, are seen in type 1 autoimmune hepatitis, generally in conjunction with antinuclear and/or smooth-muscle antibodies. In type 2 autoimmune hepatitis, a disease which occurs predominantly in girls and young women, anti-liver-kidney microsomal-1 antibodies and anti-cytosol-1 antibodies are the major circulating autoantibodies. There also are patients with variant forms of autoimmune hepatitis who have clinical and serologic findings of autoimmune hepatitis in addition to features of primary biliary cirrhosis or primary sclerosing cholangitis. The taxonomy and definitions of these variants, often referred to as overlap syndromes, are controversial. IgG4-associated cholangitis is recognized as an entity distinct from autoimmune hepatitis. Whether or not IgG4-associated autoimmune hepatitis is a distinct entity awaits a more extensive description of clinical and immuno-histological features.