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INTRODUCTION

This chapter discusses a group of nonviral conditions that result in chronic inflammation of the liver, ultimately leading to fibrosis, cirrhosis, and liver failure. The epidemiology, pathogenesis, and management of autoimmune liver disease, Wilson disease, and α1-antitrypsin deficiency are described.

AUTOIMMUNE HEPATITIS

ESSENTIALS OF DIAGNOSIS

  • Characterized by the presence of autoantibodies and elevated serum immunoglobulin G (IgG) levels.

  • More common in women than in men.

  • Diagnosis is made on the basis of serologic (abnormal liver biochemical tests, autoantibodies, elevated IgG) and histologic findings, and by ruling out other chronic liver diseases (drug-induced liver injury, viral hepatitis, inherited and metabolic liver disorders).

  • Overlap syndromes include features of other chronic liver disorders (eg, primary biliary cirrhosis, primary sclerosing cholangitis [PSC]).

General Considerations

Autoimmune hepatitis (AIH) is a heterogeneous group of chronic inflammatory hepatic disorders identified by the presence of circulating antinuclear antibody (ANA), antismooth muscle antibody (ASMA), or anti–liver kidney microsomal antibody (ALKM), and elevated serum γ-globulins. The pathogenesis of the disease is unclear, although it is believed that genetic predisposition in susceptible individuals ultimately leads to an immunologic process directed against hepatocytes. Among the many suspected inciting factors in those genetically predisposed are toxins, medications, and infectious agents. The inflammatory disorder can result in hepatocellular necrosis and collapse or in fibrosis and cirrhosis. The disease is present in all racial groups and all age groups but is more common in women than in men, with a frequency of 3.6:1. It is responsible for approximately 2–3% of pediatric liver transplantation and 4–6% of adult liver transplantation in Europe and the United States.

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Pathogenesis

The mechanism of hepatic injury in AIH is not well characterized. There appear to be both genetic and environmental influences.

AIH is classified into two distinct subtypes based on the presence of autoantibodies. The clinical relevance of this classification system is unclear as it is not certain that autoantibodies play a role in disease pathogenesis. Type 1 or “classic” autoimmune hepatitis is present in patients who test positive for ANA or ASMA, or both. ASMA is thought to be reflective of the more specific antiactin antibody (AAA) particularly when the ASMA titer is >1:320. This is the most common form and has been linked to HLA DRB 10301 (DR3) and DRB 10401 (DR4). Type 2 disease is present in patients who are positive for ALKM-1 antibody and/or antibodies directed against liver cytosol antigen (ALC-1). This form is common in Europe and ...

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