Autoimmune Hepatitis

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Chapter 354 Autoimmune Hepatitis

Autoimmune hepatitis is a chronic hepatic inflammatory process manifested by elevated serum aminotransaminase concentrations, liver-associated serum autoantibodies, and/or hypergammaglobulinemia. The target of the inflammatory process can include hepatocytes and to a lesser extent bile duct epithelium. Chronicity is determined either by duration of liver disease (typically >3-6 mo) or by evidence of chronic hepatic decompensation (hypoalbuminemia, thrombocytopenia) or physical stigmata of chronic liver disease (clubbing, spider telangiectasia, hepatosplenomegaly). The severity is variable; the affected child might have only biochemical evidence of liver dysfunction, might have stigmata of chronic liver disease, or can present in hepatic failure.

Chronic hepatitis can also be caused by persistent viral infection (Chapter 350), drugs (Chapter 355), metabolic diseases (Chapter 353), or unknown and autoimmune disorders (Table 354-1). Approximately 15-20% of chronic cases are associated with hepatitis B infection; unusually severe disease may be caused by superimposed infection with hepatitis D (a defective RNA virus that is dependent on replicating hepatitis B virus [HBV]). More than 90% of hepatitis B infections in the 1st yr of life become chronic, compared with 5-10% among older children and adults. Chronic hepatitis develops in >50% of acute hepatitis C virus infections. Patients receiving blood products or who have had massive transfusions are at increased risk. Hepatitis A or E viruses do not cause chronic hepatitis. Drugs that are commonly used in children and can cause chronic liver injury include isoniazid, methyldopa, pemoline, nitrofurantoin, dantrolene, minocycline, pemoline, and the sulfonamides. Metabolic diseases can lead to chronic hepatitis including α1-antitrypsin deficiency, inborn errors of bile acid biosynthesis, and Wilson disease. Nonalcoholic steatohepatitis, usually associated with obesity and insulin resistance, is another common cause of chronic hepatitis; it is relatively benign and responds to weight reduction and/or vitamin E therapy. Progression to cirrhosis has been described in adults and some children. In most cases, the cause of chronic hepatitis is unknown; in many, an autoimmune mechanism is suggested by the finding of serum antinuclear and anti–smooth muscle antibodies and by multisystem involvement (arthropathy, thyroiditis, rashes, Coombs-positive hemolytic anemia).

Histologic features help characterize chronic hepatitis. Subdivision of chronic hepatitis into a persistent vs active form on the basis of histologic findings is not as useful as once thought. The finding of inflammation contained within the limiting plate of the portal tract (chronic persistent hepatitis) and the absence of fibrosis or cirrhosis suggest a more benign course. The finding of activity on biopsy can predict response to antiviral therapy if hepatitis B infection is present and is a criterion used in the diagnosis of autoimmune hepatitis. Histologic features help identify the etiology; characteristic periodic acid–Schiff (PAS)-positive, diastase-resistant granules are seen in α1-antitrypsin deficiency, and macrovesicular and microvesicular neutral fat accumulation within hepatocytes is a feature of steatohepatitis. Bile duct injury can suggest an autoimmune cholangiopathy. Ultrastructural analysis might suggest distinct types of storage disorders.

Autoimmune hepatitis is a clinical constellation that suggests an immune-mediated process; it is responsive to immunosuppressive therapy (Table 354-2). Autoimmune hepatitis typically refers to a primarily hepatocyte-specific process, whereas autoimmune cholangiopathy and sclerosing cholangitis are predominated by intra- and extrahepatic bile duct injury. Overlap of the process involving both hepatocyte and bile duct directed injury may be common in children. De novo hepatitis is seen in a subset of liver transplant recipients whose initial disease was not autoimmune.

Table 354-2 CLASSIFICATION OF AUTOIMMUNE HEPATITIS

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VARIABLE TYPE 1 AUTOIMMUNE HEPATITIS TYPE 2 AUTOIMMUNE HEPATITIS
Characteristic autoantibodies Antinuclear antibody* Antibody against liver-kidney microsome 1*
Smooth-muscle antibody*  
Antiactin antibody Antibody against liver cytosol 1*
Autoantibodies against soluble liver antigen and liver-pancreas antigen  
Atypical perinuclear antineutrophil cytoplasmic antibody  
Geographic variation Worldwide Worldwide; rare in North America
Age at presentation Any age Predominantly childhood and young adulthood
Sex of patients Female in ~75% of cases Female in ~95% of cases
Association with other autoimmune diseases Common Common§
Clinical severity Broad range Generally severe
Histopathologic features at presentation Broad range Generally advanced
Treatment failure