Autoimmune Hepatitis

Chronic Liver Disease

Autoimmune hepatitis is a chronic hepatic inflammatory process manifested by elevated serum aminotransaminase concentrations, liver-associated serum autoantibodies, and/or hypergammaglobulinemia. The serological autoantibody profile defines 2 main types of autoimmune hepatitis: AIH type 1, with positivity for anti-nuclear antibodies (ANA) and/or anti–smooth muscle antibody (SMA) and AIH type 2, with positivity for anti–liver kidney microsomal type 1 antibody (anti-LKM-1). The targets 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, splenomegaly, ascites). 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 (see Chapter 358 ), drugs (see Chapter 363 ), metabolic diseases (see Chapter 361 ), fatty liver disease, or idiopathic disorders, which may have features of autoimmunity ( Table 389.1 ). 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. Transmission can occur during the perinatal period from an infected mother or in adolescents from parenteral drug abuse. Hepatitis A does not lead to chronic liver disease. Hepatitis E can become chronic in immunosuppressed patients. Drugs commonly used in children that can cause chronic liver injury, which can mimic autoimmune hepatitis, include isoniazid, methyldopa, pemoline, nitrofurantoin, dantrolene, minocycline, pemoline, and the sulfonamides. Metabolic diseases can lead to chronic hepatitis, including α ₁ -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 can progress to cirrhosis but responds to weight reduction. In many cases the cause of chronic hepatitis is unknown; in some, an autoimmune mechanism is suggested by the finding of serum antinuclear and anti–SMAs and by multisystem involvement (arthropathy, thyroiditis, rashes, Coombs-positive hemolytic anemia).

Autoimmune hepatitis is a clinical constellation that suggests an immune-mediated process; it is responsive to immunosuppressive therapy ( Table 389.2 ). Autoimmune hepatitis typically refers to a primarily hepatocyte-specific process, whereas autoimmune cholangiopathy and sclerosing cholangitis predominately involve intrahepatic and extrahepatic bile duct injury. Overlap of the process involving both hepatocyte and bile duct–directed injury may be more common in children. De novo hepatitis can be seen in a subset of liver transplant recipients whose initial disease was not autoimmune.