Evolving Drugs in the Management of Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a complex and heterogeneous disease, part of the spectrum of autoimmune liver diseases, which includes primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes (AIH-PBC/ AIH-PSC/Variants).

Recent years have witnessed a signifi cant increase in our understanding of the mechanisms of autoimmunity.

The overarching goals for developing new treatments for autoimmune liver diseases are to minimize tissue injury, improve quality of life, and increase life expectancy.

First- and second-line drugs have shown good response, but there is a clinical need for the treatment of challenging cases.

Evolving drugs for AIH include rituximab, a monoclonal antibody against CD20, leading to B-cell depletion. Doses of 375 mg/m2 are administered, with repeat dosing based on aminotransferases and CD19 counts.

B-cell activating factor (BAFF) inhibitors such as belimumab and inalumab show promise, acting as monoclonal antibodies against BAFF or BAFF receptors, inhibiting B-cell differentiation. Ongoing clinical trials involve three experimental arms.

Interleukin 2, a regulatory T-cell promoter, is under investigation in clinical trials to determine appropriate doses.

Proteasome inhibitors like zetomipzomib and TLR4 antagonists are part of the evolving landscape of drugs for AIH management.