Evolution of Therapy in Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is an immune-mediated liver disease characterized by a spectrum of clinical manifestations, ranging from asymptomatic liver enzyme abnormalities to fulminant liver failure. Despite significant achievements, the backbone of first-line AIH treatment, including corticosteroids and azathioprine, has remained nearly unchanged for 5 decades. However, up to 20% of patients experience insufficient response, loss of response, or treatment intolerance. For patients intolerant to first-line therapy, second-line options include mercaptopurine and mycophenolate mofetil (MMF), with recent debates regarding MMF's potential role in first-line treatment. A significant advancement has been the tailoring of azathioprine doses and manipulating blood levels with the addition of low-dose allopurinol by using therapeutic metabolite monitoring for patients with insufficient or lost biochemical response. Increasing experience with calcineurin inhibitors and biologic agents, particularly rituximab and infliximab, has demonstrated their efficacy as third-line options. Notably, B-cell activating factor blockade emerges as a promising future treatment. This article delves into the chronological evolution of AIH treatment, focusing on recent advances.