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There are three liver diseases in which an autoimmune mechanism
is primarily responsible for damage to the liver: autoimmune hepatitis
(AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH
after liver transplant. This chapter will review each of these three
topics.
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Definitions
and Epidemiology
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This disorder has been alternately called a variety of terms,
including active chronic hepatitis, chronic active hepatitis, chronic
aggressive hepatitis, lupoid hepatitis, plasma cell hepatitis, and, most
commonly, autoimmune chronic active hepatitis. In 1992, the International
Autoimmune Hepatitis Group (IAIHG) recommended AIH as the most appropriate
and least redundant term for this disease.1
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AIH is characterized by inflammatory liver histology, circulating
non-organ-specific autoantibodies, and elevated levels of IgG, all
in the absence of a known etiology. Two types of AIH have been described,
with the distinction made according to differing profiles of the
circulating autoantibodies. Type 1 or classic AIH is characterized
by the presence of smooth muscle antibody (SMA) and/or
anti-nuclear antibody (ANA), whereas type 2 AIH is positive for
anti-liver kidney microsomal type 1 antibody (anti-LKM-1). There
are several other antibodies, discussed below, which can also be
present (Table 27–1).
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AIH affects both children and adults. Type 1 AIH, which accounts
for roughly two-thirds of cases, has a bimodal age distribution.
One incidence peak is between 10 and 20 years of age, with the second
between 45 and 70 years of age.2 Type 2 AIH generally presents
at a younger age, often between the ages of 2 and 14 years, though not
infrequently in infancy.3,4 In both types 1 and 2 AIH,
females represent roughly 75% of cases.4 The exact
prevalence in children is unknown.
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A paradigm for the pathogenesis of AIH centers upon the concept
that in a genetically susceptible host, exposure to an environmental
agent can trigger a cascade of events, ultimately resulting in a chronic
hepatic necroinflammatory response, leading to fibrosis and cirrhosis.5
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The search for genetic predisposing factors has focused to a
large extent on the genes encoding human leukocyte antigens, located
in the major histocompatibility complex. In Caucasians, type 1 AIH
is strongly associated with the HLA-DR3 serotype and with HLA-DR4.6–8 HLA-DR3-associated
disease is more commonly found in the early onset, severe form of
disease, resulting more frequently in liver transplantation.9 HLA-DR4,
in contrast, is more common in Caucasians with late-onset disease
and appears to be ...