Comparative Effectiveness of Mycophenolate Mofetil and Tacrolimus as a Second-Line Therapy for Autoimmune Hepatitis:...

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that usually responds to corticosteroids ± azathioprine (AZA). However, some patients are intolerant or refractory to first-line therapy and require second-line immunosuppression. Mycophenolate mofetil (MMF) and tacrolimus (TAC) are commonly used alternatives, although comparative evidence is limited. This systematic review and meta-analysis evaluated the efficacy and safety of MMF and TAC in adult AIH patients who failed first-line therapy.

A systematic search of six databases identified 16 eligible studies (n = 705), including retrospective cohorts and one case series. Study quality was assessed using the Newcastle-Ottawa Scale and the MMS (methodological quality and synthesis of case series and case reports) tool.

Biochemical remission was achieved in 56% of MMF-treated patients, rising to 66% with ≥6-month follow-up. TAC showed a pooled remission rate of 66%, increasing to 67% when defined by transaminase normalization. MMF was particularly effective in AZA-intolerant patients, while TAC showed better outcomes in steroid-refractory patients. Adverse events differed: MMF was most often associated with gastrointestinal intolerance, whereas TAC was linked to tremor, hypertension, diabetes, and renal impairment. However, statistical analysis showed wide confidence intervals, and there was considerable heterogeneity across studies.

Both MMF and TAC are effective second-line therapies for AIH. MMF appears safer and better tolerated in AZA-intolerant patients, while TAC showed a modest advantage in efficacy over mycophenolate in steroid-refractory cases. Given the limitations of current evidence, including small sample sizes, heterogeneity, and lack of randomized controlled trials, treatment choice should be individualized until higher quality data are available.