Immunosuppressive Treatment Regimens in Autoimmune Hepatitis: Systematic Reviews and Meta‐Analyses Supporting AASLD Guidelines

Three key management decisions in autoimmune hepatitis concern the use of budesonide and azathioprine as first-line therapy, the choice of mycophenolate mofetil or calcineurin inhibitors for patients failing steroids and azathioprine, and the role of maintenance steroids in prevention of recurrence after liver transplantation. To address these questions, comprehensive searches were performed (without language restrictions) of several databases from their inceptions to January 8, 2019. From 1,712 citations identified, the full texts of 578 studies were reviewed, and 13 studies met criteria for systematic review. Budesonide and azathioprine were significantly superior to prednisone and azathioprine in normalizing serum aminotransferase levels after 6 months in non-cirrhotic adults (odds ratio [OR] 2.19; 95% confidence interval [CI], 1.3-3.67). However, the evidence for other outcomes was of low quality. Overall, differences in endpoint criteria and insufficiencies in data analyses precluded confident conclusions about superiority of treatment regimens. There were no significant differences in the frequencies of biochemical remission in patients with an inadequate response or intolerance to steroids and azathioprine after treatment with mycophenolate mofetil or tacrolimus (OR, 1.95; 95% CI, 0.18-20.81). The frequencies of composite outcomes of death and liver transplantation were similar for both regimens (OR 1.70; 95% CI, 0.56-3.37). The frequencies of recurrent autoimmune hepatitis after liver transplantation were also similar, regardless of whether steroids were withdrawn or continued (OR 0.27; 95% CI 0.01-7.25). Conclusions: First-line treatment with budesonide and azathioprine normalizes serum aminotransferase levels more often than prednisone and azathioprine after six months in non-cirrhotic adults. Its effectiveness in treating other presentations or reducing either mortality or need for liver transplantation remains unproven. The frequencies of biochemical remission induced by mycophenolate mofetil or tacrolimus for treatment failure or drug intolerance were comparable. Continuation of steroid therapy does not prevent recurrence post-transplant. Future studies are essential to generate evidence-based therapeutic recommendations for autoimmune hepatitis.