Methotrexate in the Treatment of Autoimmune Hepatitis

Abstract

Dear Editor:Corticosteroids and azathioprine (AZA) are standard initial treatment of autoimmune hepatitis (AIH) while up to 20% of patients do not respond, or are intolerant to this treatment. 1 In Clinical Gastroenterology and Hepatology, several reports have shown that mycophenolate mofetil, tacrolimus, 6-mercaptopurine, and 6thioguanine are effective and safe second-line therapies for AIH. 2-6 More recently, Haridy et al 7 reported efficacy and safety of methotrexate (MTX) as alternative therapy in 11 adult AIH patients. To provide additional information their findings, we present a patient who consecutively developed AIH and rheumatoid arthritis (AIH, followed by rheumatoid arthritis) and successfully managed by MTX during follow up.A 37-year-old woman was diagnosed with AIH based on a combination of autoimmune serology, elevated IgG levels, and compatible liver biopsy findings. She was initially treated by standard therapy (prednisolone combination with AZA) and full biochemical response (normalization of serum transaminases and IgG) was achieved after 5 months of therapy. Two years later, she was diagnosed with rheumatoid arthritis by the presence joint symptoms and autoimmune serology. She was switched from AZA therapy to MTX and rheumatoid arthritis-related symptoms were resolved. Currently, she is on 5 mg/day prednisolone and methotrexate (15 mg/ week), with normal serum transaminases and IgG levels in the second year of therapy.Our case along with data of Haridy et al 7 suggest that methotrexate can be used as a second-line treatment option for AIH. However, patients receiving MTX are more likely to discontinue therapy because of the drug's side effects rather than a lack of efficacy. MTX-related side effects such are as hepatotoxicity, hematopoietic suppression, and pulmonary and hepatic fibrosis can be serious in some patients. MTX is teratogenic and contraindicated during pregnancy, and also contraindicated for men aiming to father a child. 8 These disadvantages of MTX prevent its routine use in the treatment of AIH.Reply. We thank Efe et al 1,2 for their response and contribution of a further case describing the use of methotrexate (MTX) for autoimmune hepatitis. MTX has demonstrable efficacy in a number of autoimmune diseases that commonly are associated with autoimmune hepatitis such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. 3-6 MTX therefore should be considered a viable therapeutic option in patients who have additional indications such as the case described by Efe et al. 1 We agree that MTX does carry a vastly different side-effect profile to thiopurines and other second-line agents, however, there is a large repository of long-term safety data for MTX use in both rheumatologic and dermatologic literature. [7][8][9] Other alternatives need to be considered in patients of child-bearing age or considering pregnancy.

Autoimmune Hepatitis: a Review of Established and Evolving Treatments

“…It has recently been suggested that a combination of these mechanisms may be the key to its full immunosuppressant efficacy [95]. A successful use of MTX in treatment of AIH has been repeatedly reported since the late 1990s [50,96,97]. However, all of these reports only described successful treatment of single patients, including two pediatric cases [98].…”