Second Line Therapy in Autoimmune Hepatitis: is Mycophenolate Mofetil an effective option?

Autoimmune hepatitis (AIH) has a good prognosis when the inflammatory reaction is sufficiently suppressed and the development of cirrhosis is prevented. Steroids and Azathioprin (AZA) are established for first-line-therapy. However, there is no established regimen in case of ineffectiveness of this combination. Results from a small study suggest Mycophenolate Mofetil (MMF) to be effective in patients with AZA intolerance. However, these data also showed MMF ineffectiveness in the majority of patients with prior non-response to AZA. Therefore, the aim of this study was to further evaluate second-line regime with MMF in patients with AIH after failure of standard steroid and AZA therapy.

In our large cohort of 315 patients with AIH 44 patients (age median 55 years, range 35–84; 33 female, 7 male) were treated with MMF after standard therapy with steroid and AZA. These patients were now analyzed retrospectively. Four patients were excluded because of missing data. The data of 11 patients from our ambulance are partly published by Hennes 2008.

AIH diagnosis was proven according to the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis from 2008. MMF remission was defined as minimal three month MMF treatment and AST increased maximal to twice upper normal limit. Cases with laboratory response to MMF but severe side effects, leading to discontinuation of MMF were also defined as non-responder.

28 of 40 patients received MMF due to severe side effects under AZA, 11 patients due to non response. One patient was excluded after discontinuation of MMF therapy with respect to pregnancy.

Of the 28 patients, who changed from AZA to MMF due to side effects, 17 had responded to MMF treatment. 11 showed no remission. However, this group included two patients still on MMF, who experienced a single mild exacerbation during 3 year observation period (36 and 37 month). Thereafter, the AIH was sufficiently controlled over the last 17 and 36 month, respectively.

In contrast, only one of 11 patients reached remission under MMF therapy when standard therapy had previously failed.

In summary, we confirmed the results published by Hennes 2008 in a slightly larger cohort and a longer observation period (median 35, range 1–133 month): MMF is a good option when remission is reached with AZA, but therapy has to be changed due to AZA side effects.