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MINERVA GASTROENTEROLOGICA E DIETOLOGICA
A Journal on Gastroenterology, Nutrition and Dietetics
Indexed/Abstracted in: CAB, EMBASE, PubMed/MEDLINE, Scopus, Emerging Sources Citation Index
Minerva Gastroenterologica e Dietologica 2007 March;53(1):43-78
Evolving concepts in the diagnosis, pathogenesis and treatment of autoimmune hepatitis
Czaja A. J.
Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester, MN, USA
The diagnostic criteria for autoimmune hepatitis have been codified, and a scoring system can quantify the strength of the diagnosis. Centrilo-bular (zone 3) necrosis signifies acute disease, and severe acute and fulminant presentations of autoimmune hepatitis are recognized. The absence of symptoms at presentation may identify some patients who do not require treatment, but therapeutic decisions must be based on disease activity not symptoms, especially since 26-70% of asymptomatic patients become symptomatic. Elderly patients have more advanced disease at presentation, but they respond well to treatment. Antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, actin, and liver cytosol type 1 have prognostic value. Molecular mimicry between viral and self-antigens is the likely basis for the autoimmune response. Susceptibility alleles optimize antigen presentation. Polymorphisms influence immunocyte activation, counter-regulatory actions within the cytokine milieu, and apoptotic pathways for hepatocyte and immunocyte death. Perturbations in the populations of T regulatory cells and natural killer T cells disrupt immune homeostasis. Cyclosporine, mycophenolate mofetil, and budesonide afford new treatment opportunities, and molecular interventions at critical pathogenic pathways are feasible, especially within the cytokine network. Confident animal models of the human disease and a collaborative network of clinical investigators are the requisites for progress.