Beyond Corticosteroids and Azathioprine: Emerging Treatment Options in Autoimmune Hepatitis — A Literature Review
Abstract
Introduction: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease with a global pooled prevalence of 15.65 cases per 100,000 inhabitants and rising incidence. First-line corticosteroids and azathioprine or mycophenolate mofetil induce remission in most patients, some fail to respond, relapse after treatment withdrawal, or experience treatment-limiting adverse effects. Aim: To evaluate the evidence for alternatives to standard therapy and compare their efficacy, safety, and current place in clinical practice. Methods: PubMed and PubMed Central were searched for studies published 2006–2026, prioritising systematic reviews, meta-analyses, randomised trials, and comparative cohort studies; case series were included only where stronger evidence was unavailable. The 2025 EASL guideline was reviewed. Results: Budesonide with azathioprine is supported by a multicentre randomised trial (n = 208) and meta-analytic data showing fewer steroid-related adverse effects, although its remission advantage is inconsistent across study designs. Mycophenolate mofetil achieved higher remission than azathioprine in the only randomised induction comparison (56.4% vs. 29.0% at 24 weeks; n = 70), and EASL now recognises it as a first-line alternative. Three meta-analyses consistently found better tolerability but reached different conclusions regarding remission advantage. Tacrolimus achieved 66% pooled second-line remission versus 56% for mycophenolate mofetil, on predominantly retrospective evidence. Evidence for mTOR inhibitors and biological agents is limited to small case series. Conclusion: Confidence is highest for the tolerability advantages of budesonide and mycophenolate mofetil and lower for their comparative efficacy; it is low to moderate for tacrolimus and low for mTOR inhibitors and biological agents. Third- and later-line treatment should remain individualised pending randomised comparative studies.