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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.
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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
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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.
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Pathophysiology
and Genetics
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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).
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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 ...