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

Objectives

Uncertainty remains about many aspects of first-line treatment of autoimmune hepatitis (AIH).

Design

Systemic review with meta-analysis (MA).

Data sources

Bespoke AIH Endnote Library, updated to 30 June 2024.

Eligibility criteria

Randomised controlled trials (RCTs) and comparative cohort studies including adult patients with AIH, reporting death/transplantation, biochemical response (BR) and/or adverse effects (AEs).

Data extraction and synthesis

Data pooled in MA as relative risk (RR) under random effects. Risk of bias (ROB) assessed using Cochrane ROB-2 and ROBINS-1 tools.

Results

From seven RCTs (five with low and two with some ROB) and 18 cohort studies (12 moderate ROB, six high for death/transplant), we found lower death/transplantation rates in (a) patients receiving pred+/−aza (vs no pred): overall (RR 0.38 (95% CI 0.20 to 0.74)), in patients without symptoms (0.38 (0.19–0.75)), without cirrhosis (0.30 (0.14–0.65)), and with decompensated cirrhosis (RR 0.38 (0.23–0.61)), and (b) patients receiving pred+aza (vs pred alone) (0.38 (0.22–0.65)). Patients receiving higher (vs lower) initial pred doses had similar BR rates (RR 1.07 (0.92–1.24)) and mortality (0.71 (0.25–2.05)) but more AEs (1.73 (1.17–2.55)). Patients receiving bud (vs pred) had similar BR rates (RR 0.99 (0.71–1.39)), with fewer cosmetic AEs (0.46 (0.34–0.62)). Patients receiving mycophenolate mofetil (MMF) (vs aza) had similar BR rates (RR 1.32 (0.73–2.38)) and fewer AEs requiring drug cessation (0.20 (0.09–0.43)).

Conclusions

Mortality is lower in pred-treated (vs untreated) patients, overall and in several subgroups, and in those receiving pred+aza (vs pred). Higher initial pred doses confer no clear benefit and cause more AEs. Bud (vs pred) achieves similar BR rates, with fewer cosmetic AEs. MMF (vs aza) achieves similar BR rates, with fewer serious AEs.