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Meta-Analysis
. 2025 Mar 28;12(1):e001549.
doi: 10.1136/bmjgast-2024-001549.

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

Dermot Gleeson  1 , Marrissa Martyn-StJames  2 , Ye Oo  3   4 , Sarah Flatley  5
Affiliations
Meta-Analysis

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

Dermot Gleeson et al. BMJ Open Gastroenterol. .

Abstract

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.

Keywords: AUTOIMMUNE DISEASE; AUTOIMMUNE HEPATITIS; STEROID-SPARING EFFICACY.

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Conflict of interest statement

Competing interests: DG: Invited speaker (on PSC) Dr Falk sponsored symposium 2023; hospitality, no honorarium. Other authors: no interests declared.

Figures

Figure 1
Figure 1. Estimations of risk of bias. (A) Randomised controlled trials (Cochrane ROB tool). (B) Observational studies (ROBINS-1 tool).
Figure 2
Figure 2. Comparison of all-cause deaths/transplants in patients receiving steroids vs no steroids. (A) All patients. Steroids±azathioprine vs placebo or azathioprine alone. (B) All patients. Steroids plus azathioprine vs steroid alone. (C) Asymptomatic patients—steroids±azathioprine vs placebo or azathioprine alone.
Figure 3
Figure 3. Comparison of high and low initial predniso(lo)ne doses. (A) Biochemical remission after 6 months. (B) All-cause death or transplant. (C) Cosmetic adverse effects. (D) Diabetes.
Figure 4
Figure 4. Comparison of budesonide and prednis(ol)one (both with azathioprine). (A) Biochemical remission after 6 months. (B) Any adverse effect. (C) Cosmetic adverse effects. (D) Diabetes.
See this image and copyright information in PMC

References

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