What is the optimal first-line treatment of autoimmune hepatitis? A systematic review with meta-analysis of randomised trials and comparative cohort studies.

Summary

This meta-analysis of 7 RCTs and 18 cohort studies shows that prednisone reduces death/transplantation in autoimmune hepatitis, with additional benefit from combining azathioprine. Higher initial steroid doses provide no clear efficacy advantage and increase adverse events. Budesonide offers similar biochemical response to prednisone with fewer cosmetic adverse effects, and mycophenolate is an alternative to azathioprine with fewer serious AEs.

Key Findings

• Prednisone (± azathioprine) reduced death/transplantation versus no prednisone across several subgroups (overall RR 0.38, 95% CI 0.20–0.74).
• Prednisone plus azathioprine lowered death/transplantation compared with prednisone alone (RR 0.38, 95% CI 0.22–0.65).
• Higher initial prednisone doses did not improve biochemical response (RR 1.07) and increased adverse events (RR 1.73).
• Budesonide achieved similar biochemical response to prednisone (RR 0.99) with fewer cosmetic adverse events (RR 0.46); MMF had similar efficacy to azathioprine with fewer discontinuation-requiring AEs (RR 0.20).

Clinical Implications

Use prednisone plus azathioprine as standard first-line where tolerated; avoid high initial steroid doses due to increased AEs without efficacy gain. Consider budesonide when minimizing cosmetic steroid effects is a priority and mycophenolate for azathioprine intolerance.

Limitations

• Heterogeneity and moderate-to-high risk of bias in several cohort studies, especially for mortality outcomes.
• Total pooled sample size and subgroup-specific data not fully detailed in the abstract.

Future Directions

Head-to-head RCTs of budesonide vs prednisone stratified by disease severity; dose-optimization trials; pragmatic trials comparing azathioprine vs mycophenolate with long-term outcomes and patient-centered (including cosmetic) AEs.