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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 2005 December;51(4):313-34
Diverse manifestations and evolving treatments of autoimmune hepatitis
Czaja A. J.
Autoimmune hepatitis has a global occurrence and diverse manifestations. Patients are frequently asymptomatic (34%), and an acute, even fulminant, presentation is possible. Concurrent immune disorders may obscure the liver disease, and perivenular (Rappaport zone 3) necrosis is within the histological spectrum. Clinical phenotypes and outcomes vary among different ethnic groups, and genetic factors strongly affect susceptibility. Non-disease specific autoimmune modifiers include female gender and gene polymorphisms that affect immunocyte activation and differentiation. Antibodies to soluble liver antigen/liver pancreas may have prognostic importance and reflect a genetic propensity for severe disease. Subtypes based on serological profiles do not have distinctive outcomes or therapies. Variant forms include patients with bile duct injury or loss, absence of conventional serological markers, abnormal cholangiograms, or coincidental hepatitis C. Treatment is empiric and based on the predominant manifestations (hepatitic, cholestatic, or viral). New treatment strategies must be strengthened by predictive indices that accurately forecast individual differences in disease outcome. Drugs with site-specific actions on immunocyte activation and proliferation (cyclosporine, tacrolimus and myco-phenolate mofetil) must be assessed by clinical trial, and site-specific molecular interventions (blocking peptides, recombinant immune modulators, T cell vaccination, oral tolerance, gene silencing and gene therapy) require confident experimental animal models for evaluation. Better prognostic indices, new immunosuppressive agents, and site-specific molecular interventions promise to improve care.