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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 two types of AIH that are categorized based on the autoantibody profile. Type I 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 II AIH accounts for one-third of all cases, and is characterized by positivity for anti-liver-kidney-microsomal type 1 (LKM-1) antibody and/or anti-liver cytosol-1. This group tends to be younger, and to have a higher incidence of partial IgA deficiency and acute liver failure at presentation.1-4


Both types of autoimmune hepatitis (AIH) are more predominant in females.1 Twenty percent of patients have associated autoimmunity upon presentation, and 40% report a positive family history of autoimmune disorders. AIH is more frequent in women than men. Untreated mortality can approach 50% within 5 years of diagnosis, and 90% after 10 years. 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. Some patients are positive for the atypical perinuclear antibody pANNA. Close to 50% of these patients have an overlap syndrome (with primary sclerosing cholangitis) affecting their ultimate outcome and response to medical therapy. A higher proportion of patients in this group tend to have advanced fibrosis upon presentation and a higher association with autoimmune polyendocrinopathy.

Pathophysiology and Genetics

Autoimmune hepatitis (AIH) is a multifactorial polygenetic disease. As with many autoimmune disorders, individuals with certain HLA backgrounds (DR3, DR7, DR13) are at increased risk for AIH. The mechanism of liver injury includes involvement of T cells, NK cells, Macrophages, B cells, and NKT cells. Patients reported in 2 different series show evidence of decreased CD8 lymphocytes, impaired suppressor cells function2 and T regulatory cell function.3Autoreactive reactive T cells also are reported to induce autoantibody production by autologus B cells. In Type II AIH, the target of this humoral response is the cytochrome P450 2D6 (CYP2D6).

Clinical Features

Patients often present with an acute hepatitis, accompanied by jaundice and fatigue. The clinical exam can reveal evidence of chronic liver disease. Occasionally, hepatomegaly, splenomegaly, complications of portal hypertension, and skin stigmata of chronic liver disease such as spider angioma can be the presenting feature. Autoimmune hepatitis (AIH) can have a similar clinical presentation to viral ...

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