Can we cure autoimmune hepatitis?

Autoimmune hepatitis (AIH) is an organ-specific autoimmune disorder mainly affecting females and characterized by seropositivity for autoantibodies, hypergammaglobulinemia, and histological evidence of interface hepatitis. Liver damage in AIH is perpetrated by multiple immune cell subsets, including B, T lymphocytes, and macrophages. Dysfunction of regulatory T cells (Tregs), an immune subset central to immunotolerance, plays an important permissive role by enabling effector lymphocytes to act unopposed and perpetuate autoimmune liver injury. Corticosteroids and azathioprine are the mainstay of treatment, resulting in disease remission in 80-90% of cases. Second- and third-line treatment, including mycophenolate mofetil, calcineurin inhibitors, and anti-B lymphocyte strategies, are used in difficult-to-treat cases or intolerant patients. Although controlling inflammation, these immunosuppressants are associated with significant side effects that impact patients' quality of life and adherence to treatment and, importantly, do not enable immune tolerance reconstitution. Strategies based on adoptive transfer of or ex vivo expansion of Tregs would enable limiting effector cell immunity while reconstituting immune tolerance. Additional studies into the mechanisms resulting in Treg dysfunction at both systemic and tissue levels are warranted to engineer more potent, stable, and long-lasting Tregs to be used in immunotherapy. Restoring Treg pool would be a key step forward toward the cure of this autoimmune condition and other autoimmune diseases with similar pathogenesis.