Established and novel therapeutic options for autoimmune hepatitis

Abstract

Autoimmune hepatitis is an immune-mediated disorder characterised by hypergammaglobulinaemia, autoantibodies, and interface hepatitis. The mainstay of treatment is non-specific immunosuppression, consisting of steroids with or without azathioprine. Although most patients respond satisfactorily to steroid and thiopurine-based treatment regimens, up to 40% relapse and 10% undergo liver transplantation. The cause of autoimmune hepatitis is unknown, but evidence implicates both genetic and environmental factors in its pathogenesis. An imbalance between effector and regulatory mechanisms leads to the breakdown of immune tolerance and the consequent development of an autoimmune attack. Signalling pathways that have been implicated in the pathogenesis of autoimmune hepatitis involve the proinflammatory cytokines interferon-γ, IL-12, tumour necrosis factor-α, IL-6, and IL-23. Numerical and functional defects of regulatory T cells have a permissive role that enables autoimmune liver injury to occur and persist. New therapeutic strategies are needed, with the aim of obtaining long-lasting disease remission without inducing non-specific immunosuppression and a focus on inhibiting the intrahepatic proinflammatory milieu or expanding the pool of regulatory T cells, or both.