Autoimmune Hepatitis: Current and Future Therapeutic Options

Iliana Doycheva; Kymberly D. Watt; Aliya F. Gulamhusein


Liver International. 2019;39(6):1002-1013. 

In This Article

Abstract and Introduction


Autoimmune hepatitis (AIH) is a rare immune-mediated liver disease with few major advances in treatment options over the last several decades. Available options are effective in most patients albeit are imprecise in their mechanisms. Novel and more tolerable induction regimens and alternative options for management of patients intolerant or with suboptimal response to traditional therapies including in the post-transplant setting remain an important unmet need. This review aims to summarize recent data on pharmacological options and investigational drugs in development for patients with AIH. Standard therapy using prednisone with or without azathioprine remains the mainstay of therapy and is effective in most patients. Budesonide may be considered for induction in early disease and in those with mild fibrosis, but has not been approved for maintenance therapy. Mycophenolate mofetil (MMF) in combination with steroids might be an alternative first-line therapy, but results from a randomized trial are awaited. MMF as a second-line maintenance agent has moderate efficacy though more frequent adverse events in patients with cirrhosis may be seen. Tacrolimus may be an equally effective second-line option particularly in non-responders, but data remain limited. Management of recurrent AIH post-liver transplantation remains controversial with insufficient data to support long-term steroid use. Moving forward, expanding the scope of therapeutic options to include biologics including B-cell depleting agents may be a promising step. Recent insights in understanding the pathogenesis of AIH could serve as a basis for future therapies, including the elucidation of different immunoregulatory pathways and the potential role of the intestinal microbiome.


Autoimmune hepatitis (AIH) is a liver-specific autoimmune disease that typically presents with hypergammaglobulinemia, characteristic circulating autoantibodies and histological evidence of interface hepatitis. Successful treatment aims at reducing inflammation and preventing progressive fibrosis while minimizing side effects associated with therapy.[1] Standard treatment approaches have remained static for decades, since prednisolone with or without azathioprine (AZA) was first introduced in the 1950s-1960s.[2] This treatment remains the mainstay therapy for good reason, with high efficacy and improved outcomes, but important areas of unmet need include more tolerable steroid-free induction regimens, second-line therapy for patients refractory or intolerant to conventional therapy, and management of recurrent AIH (rAIH) post-liver transplantation (LT).