Autoimmune hepatitis: special groups and treatment gaps

Autoimmune hepatitis (AIH) is a rare, complex and chronic immune-mediated disease in which loss of tolerance to hepatocyte antigens leads to T-cell-driven liver inflammation, typically associated with autoantibodies and elevated IgG. The understanding of disease mechanisms is limited, patient presentations are heterogeneous, and clinical care varies. Predniso(lo)ne and azathioprine or mycophenolate mofetil are the first-line treatments. These medications are life-saving, but lack specificity, and are marred by side-effect profiles that negatively affect adherence and quality of life. Less than 70% of patients achieve a complete biochemical response (normalization of aminotransferases and IgG) by 6 months, and more than 20% develop side effects that require discontinuation. In addition, current medications have high rates of relapse after discontinuation. Evidence of second- and third-line treatments is mainly built on real-world studies without control groups. In addition, people with AIH experience symptoms that affect their well-being, such as fatigue, depression, anxiety, cognitive dysfunction and mood changes. Several gaps in AIH management persist, including a lack of validated questionnaires to capture specific symptoms and complaints, lack of recognized endpoints for clinical trials supported by regulatory agencies, and special AIH populations are understudied and outcomes beyond liver enzymes are underrepresented. In this review, we provide a detailed appraisal of current gaps in the management, discuss special populations, and recent advancements of new agents for AIH, summarizing evidence regarding how these agents could reduce the side effects of current treatment, potentially improving the quality of life of people living with AIH.