Objective: To advocate formal subclassification of autoimmune hepatitis into two types based on the presence of mutually exclusive immunoserological markers, target antigen diversity, contrasting genetic predispositions, and differences in clinical profile and behavior.
Methods: Relevant references in English were identified through a Medline Search (1984-1994) and through a personal library of journals and reprints.
Results: Antinuclear antibodies and/or smooth-muscle antibodies are mutually exclusive of antibodies to liver/kidney microsome type 1. The cytochrome monooxygenase P450 IID6 is the target autoantigen for patients with antibodies to liver/kidney microsome type 1, and patients with these autoantibodies are different from others. The human lymphocyte antigens DR3 and DR4 are risk factors for patients with antinuclear and/or smooth-muscle antibodies, whereas the B14, DR3, and C4A-QO antigens are common in patients with antibodies to liver/kidney microsome type 1. Patients with antibodies to liver/kidney type 1 are younger, and they more commonly have concurrent organ-specific autoantibodies and/or immunological diseases than counterparts with antinuclear and/or smooth-muscle antibodies. They also progress to cirrhosis more frequently.
Conclusions: Two distinct types of autoimmune hepatitis can be defined by immunoserological markers, genetic predispositions, autoantigen status, and clinical features. Each should be recognized as a valid and independent entity.