Autoimmune liver disorders in childhood include
autoimmune hepatitis (AIH) and AIH/
sclerosing cholangitis overlap syndrome (henceforth referred to as autoimmune
sclerosing cholangitis, ASC). These inflammatory liver disorders are characterised histologically by interface
hepatitis, biochemically by elevated
transaminase levels, and serologically by
autoantibodies and increased levels of
immunoglobulin G. AIH is particularly aggressive in children and progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment, 80% of patients achieve remission and long-term survival. For non-responders and difficult-to-treat patients, novel and more effective therapeutic approaches are sought. ASC responds to the same treatment used for AIH in regards to parenchymal
inflammation, but
bile duct disease progresses in about 50% of cases, leading to a worse prognosis and a higher
liver transplantation requirement; moreover, it has a high recurrence rate after transplant. Progression of
liver disease and recurrence after transplant are more common in patients with associated poorly controlled
inflammatory bowel disease. Though the mechanisms underlying the pathogenesis of liver autoimmunity are not fully understood, genetic and environmental factors are likely to be involved. A deeper understanding of the pathogenesis of these conditions will contribute to the development of novel treatments, aimed ultimately at the restoration of tolerance to liver-derived
antigens.