Mycophenolate mofetil to the rescue in autoimmune hepatitis: A fresh sprout on the decision tree

Abstract

The concept that some patients with autoimmune hepatitis may not respond well to corticosteroid therapy can be difficult to accept. Success breeds complacency, and few treatments of chronic liver disease have been as successful as corticosteroid therapy. Prednisone alone or a lower dose in combination with azathioprine induces clinical, laboratory and histological improvement in 80% of adults with autoimmune hepatitis within 3 years [1–4], normalizes 10and 20-year life-expectancies [5], and prevents or reduces hepatic fibrosis in 79% [6]. Similar but less comprehensive results have been reported in children [7–9], and expectations of treatment success are justifiably high in both patient populations. The report by Aw and colleagues that 14% of children fail to respond or tolerate corticosteroid treatment [10] complements the experience in adults [11,12], and it is an important reality check. Not only does it re-confirm the need for a rescue therapy in autoimmune hepatitis, but it also strengthens the support for mycophenolate mofetil in this role [10]. Mycophenolate mofetil is a prodrug hydrolyzed by liver esterases to produce the active metabolite, mycophenolic acid, which in turn acts as a non-competitive, reversible inhibitor of inosine monophosphate dehydrogenase [13–16]. Inosine monophosphate dehydrogenase is the rate-limiting enzyme for de novo synthesis of purines, and by inhibiting its action, mycophenolate mofetil