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

Background: 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 azathioprine 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 2400 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 and increased CBR compared with the AZA group (RR = 1.44, 95% CI = 1.03 to 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 revealed a significant association between the MMF group and increased biochemical remission compared with the AZA group in patients with IgG levels of less than 2400 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.

背景：硫唑嘌呤（azathioprine, AZA）是自身免疫性肝炎（autoimmune hepatitis, AIH）诱导治疗与维持应答的标准方案，但往往需要终身给药。泼尼松龙联合硫唑嘌呤的联合治疗方案在疗效与耐受性方面存在显著顾虑，尤其是在停用AZA后复发率居高不下的情况下。因此，亟需探索AIH的替代治疗方案。本项系统评价与荟萃分析对比了联合泼尼松龙的吗替麦考酚酯（mycophenolate mofetil, MMF）与AZA方案治疗AIH的疗效与安全性。

方法：检索PubMed、Cochrane、Scopus及Web of Science数据库，筛选比较AZA与MMF治疗AIH的随机对照试验（randomized clinical trial, RCT）和队列研究。最终纳入4项对比MMF组与AZA组激素撤除与完全生化应答（complete biochemical response, CBR）的研究。根据年龄（50岁以上与50岁以下）及IgG水平（2400 mg/dL以上与2400 mg/dL以下）开展亚组分析。采用RevMan（版本5.4）软件进行荟萃分析。

结果：最终纳入4项研究（含3项队列研究与1项随机对照试验），共计505例患者。合并分析结果显示，相较于AZA组，MMF组的完全生化应答率显著提升（相对风险RR=1.44，95%置信区间CI=1.03~2.01，P=0.03）；两组在激素撤除率方面无显著差异。按年龄分层的亚组分析显示，在50岁以上的患者中，MMF组的完全生化应答率显著高于AZA组（RR=1.63，95%CI=1.00~2.64，P=0.05）。IgG亚组分析显示，在IgG水平低于2400 mg/dL的患者中，MMF组的生化缓解率显著高于AZA组（RR=1.63，95%CI=1.00~2.64，P=0.05）。

结论：AIH患者使用MMF相较于AZA，与更高的完全生化应答率显著相关；两组在激素撤除率方面无显著关联。未来仍需开展进一步研究，以全面阐明不同亚群AIH患者的最优治疗策略。