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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.

Definitions and Epidemiology

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

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).

Table 27–1. Classification of Autoantibodies in Autoimmune Hepatitis

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.


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

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 ...

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