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Autoimmune liver disorders result from a spectrum of immune dysregulation where the liver can be the only organ affected or may be part of a systemic multiorgan disorder with the inflammatory response being mediated by systemic or locally produced (portal system) cytokines. The immunogenic target varies and may include the liver parenchyma, bile duct epithelium, or vasculature, with overlap syndromes that include both biliary and parenchymal involvement being increasingly recognized among children. Clinical manifestations vary depending upon the pattern of involvement.


There are 2 types of autoimmune hepatitis (AIH) that are categorized based on the autoantibody profile. Type 1 AIH accounts for two-thirds of all cases, and is characterized by positivity for antinuclear antibody (ANA), antismooth muscle antibody (SMA), or anti–F-actin antibodies. Type 2 AIH accounts for one-third of all cases, and is characterized by positivity for anti–liver/kidney microsomal type 1 (LKM-1) antibody, anti-LKM-3 antibody and/or anti–liver cytosol type 1. This latter group tends to be younger and to have a higher incidence of partial IgA deficiency and acute liver failure at presentation.


Autoimmune hepatitis is a multifactorial polygenetic disease. The strongest genetic associations are found within genes of the HLA region, particularly DR7, DR3, and DR4. The associations with HLA-DR3 and HLA-DR4 are considered strong enough to contribute to the diagnosis of AIH according the revised diagnostic scoring system designed by the International Autoimmune Hepatitis Group (IAIHG). HLA-DR7 and HLA-DR3 confer susceptibility to AIH type 2. The mechanism of liver injury includes involvement of T cells, NK cells, macrophages, B cells, and NKT cells. Patients show evidence of decreased CD8 lymphocytes and impaired suppressor cell function. Autoreactive T cells also are reported to induce autoantibody production through autologous B cells. In type 2 AIH, the target of this humoral response is the cytochrome P450 2D6 (CYP2D6). Both the number and function of professional regulatory T cells (Tregs) in peripheral blood in children with AIH have been found to be impaired. Treg activity is increased during active disease but insufficient to suppress the aberrant autoimmune response.

Autoimmune hepatitis is a progressive inflammatory liver disorder affecting mainly females. Twenty percent of patients have associated autoimmune disorders upon presentation, and 40% report a positive family history of autoimmune disorders. Autoimmune hepatitis type 2 can be part of autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy (APECED) syndrome, an autosomal genetic disorder in which the liver disease is reportedly present in 20% of cases. Autoimmune hepatitis is more frequent in women than in men. Untreated, mortality can approach 50% within 5 years of diagnosis, and 90% after 10 years from cirrhosis and liver failure. Its prevalence in the pediatric age group is unknown, but it is estimated to account for 10% of all new referrals for liver disease in large pediatric hepatology centers in North America and Europe. A ...

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