Autoimmune hepatitis: Focusing on treatments other than steroids

BACKGROUND: Corticosteroid therapy has been the time-honoured treatment for autoimmune hepatitis; however, the emergence of new immunosuppressive agents has afforded opportunities to improve or replace the standard regimens. OBJECTIVE: To describe technological advances and feasible treatment interventions that promise to supplant the current generation of corticosteroids. METHODS: A review of the MEDLINE database for published experiences from 1984 to 2011 was conducted. RESULTS: Cyclosporine and tacrolimus have been uniformly successful as salvage therapies for steroid-refractory autoimmune hepatitis. Ten reports of cyclosporine therapy involving 133 patients had positive outcomes in 93%, whereas therapy with tacrolimus in three reports involving 41 patients had positive outcomes in 98%. Salvage therapy with mycophenolate mofetil had a favourable outcome in 47%, especially in patients with azathioprine intolerance. Front-line therapy with mycophenolate mofetil normalized liver parameters in 88% and allowed corticosteroid tapering in 58%. Front-line therapy with budesonide combined with azathioprine for six months normalized liver parameters more frequently ( 47% versus 18%) and with fewer side effects ( 28% versus 53%) than prednisone combined with azathioprine. Monoclonal antibodies to CD3 and recombinant cytotoxic T lymphocyte antigen 4 fused with immunoglobulin represent feasible molecular interventions for study in autoimmune hepatitis. DISCUSSION: Nonstandard drug therapies must be used in highly selected clinical situations including steroid failure ( calcineurin inhibitors), azathioprine intolerance ( mycophenolate mofetil), and mild disease or fragile patients ( budesonide combined with azathioprine). Molecular interventions for autoimmune hepatitis are feasible for study because of their use in other immune-mediated diseases. CONCLUSION: Opportunities to improve or replace standard corticosteroid regimens have emerged.