Comparative Efficacy of Mycophenolate Mofetil vs. Azathioprine in Autoimmune Hepatitis: A Systematic Review and Meta-Analysis

Introduction: Azathioprine (AZA) is the standard treatment for both induction and maintenance of response in autoimmune hepatitis (AIH). However, lifelong administration is often required, and the combination therapy of prednisolone and AZA raises significant concerns regarding efficacy and tolerability, especially given the high relapse rates following AZA cessation. Consequently, there is a need to explore alternative treatment options. This systematic review and meta-analysis compared the efficacy and safety of mycophenolate mofetil (MMF) versus AZA, combined with prednisolone, for treating AIH. Methods: PubMed, Cochrane, Scopus, and Web of Science were searched to identify randomized clinical trials and cohort studies comparing AZA and MMF for treating AIH. Four studies compared steroid withdrawal and complete biochemical response (CBR) between the MMF and AZA groups. Subgroup analyses were performed based on age (above and below 50 years) and IgG levels (above and below 2,400 mg/dL). RevMan (version 5.4) software was used for meta-analysis. Results: Four studies (three cohort studies and one RCT) comprising 505 patients were included in the final analysis. The pooled analysis showed a statistically significant association between the MMF group, while it increased CBR compared with the AZA group (RR = 1.44, 95% CI = 1.03–2.01, p value = 0.03), with no significant difference between the two groups regarding steroid withdrawal. Subgroup analysis by age revealed a significant association between the MMF group and increased CBR in patients over 50 years (RR = 1.63, 95% CI = 1.00–2.64, p value = 0.05). IgG subgroup analysis indicated a significant association between the MMF group and increased biochemical remission compared with the AZA group in patients with IgG levels less than 2,400 mg/dL (RR = 1.63, 95% CI = 1.00–2.64, p value = 0.05). Conclusion: The use of MMF was significantly associated with increased CBR compared to AZA in patients with AIH. Additionally, there was no significant association between the two groups regarding steroid withdrawal. Further research is needed to fully elucidate the optimal treatment strategy for AIH patients across different subpopulations.