Abstract
The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation than those with HLA genotype DRB1*0401. Therapy to the point when liver test results and histological findings are normal reduces, but does not eliminate, the occurrence of relapse. Treatment failure warrants reassessment with regard to the accuracy of the original diagnosis and the exclusion of variant forms of hepatitis or concomitant alternative diseases. Ciclosporin might be effective as short-term, front-line therapy in infants and adults, and calcineurin inhibitors might salvage patients who are refractory to corticosteroid regimens. Mycophenolate mofetil can induce an improvement in laboratory test results and reduce the requirement for corticosteroids. Sirolimus is effective for treatment of de novo autoimmune hepatitis that develops after liver transplantation. Synthetic peptides that block autoantigen presentation, cytokine manipulations, oral tolerance regimens, T-cell vaccination, and gene therapy are all interventions that will be able to emerge after a reliable animal model of the human disease has been developed.
Key Points
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Corticosteroid therapy is an effective treatment for autoimmune hepatitis but is limited by its adverse effects and inability to consistently induce an inactive state
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Conventional corticosteroid regimens remain the firstline treatment, and modifications of these regimens can control suboptimal responses
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Corticosteroid treatment must ideally be continued until resolution of symptoms, laboratory indices of liver inflammation, and histological features of disease activity
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Calcineurin inhibitors have been used more commonly as salvage therapies than have other immunosuppressive drugs, but their efficacy, safety and superiority over conventional treatments are uncertain
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Novel immunosuppressant drugs and immune modulators have been used only in small clinical experiences, and they have not been endorsed as effective strategies
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Progress requires reliable animal models of the human disease and a multicenter network of clinical investigators who can evaluate new interventions quickly and rigorously
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Montano Loza, A., Czaja, A. Current therapy for autoimmune hepatitis. Nat Rev Gastroenterol Hepatol 4, 202–214 (2007). https://doi.org/10.1038/ncpgasthep0768
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DOI: https://doi.org/10.1038/ncpgasthep0768
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