Hepatitis, Autoimmune

Key Features

Essentials of Diagnosis

• Chronic hepatitis with high serum globulins and characteristic liver histology

• Antinuclear antibody (ANA) and/or smooth muscle antibody positive

• Usually occurs in young to middle-aged women

• Responds to corticosteroids

General Considerations

• The onset is usually insidious

• About 25% of cases present with acute severe hepatitis (and occasionally acute liver failure)

• Some cases follow

  • A viral illness, such as

    • Hepatitis A

    • Epstein-Barr infection

    • Measles

  • Exposure to a drug or toxin, such as

    • Nitrofurantoin

    • Minocycline

    • Hydralazine

    • Methyldopa

    • Infliximab

    • Immune checkpoint inhibitor

• Patients with autoimmune hepatitis are at increased risk for cirrhosis which, in turn, increases the risk of hepatocellular carcinoma (at a rate of about 1% per year)

• The risk of autoimmune hepatitis is increased in first-degree relatives of affected patients

• Simplified diagnostic criteria are based on

  • Detection of autoantibodies (1 or 2 points depending on titers)

  • Elevated IgG levels (1 or 2 points depending on levels)

  • Characteristic histologic features (1 or 2 points depending on how typical the features are)

  • Exclusion of viral hepatitis (2 points)

• Score of 6 indicates probable and a score of 7 indicates definite autoimmune hepatitis

• Diagnostic criteria for an overlap of autoimmune hepatitis and primary biliary cholangitis ("Paris criteria") have been proposed

Demographics

• Though usually a disease of young women, autoimmune hepatitis can occur in either sex at any age

• Affected younger persons are often positive for HLA-B8 and -DR3; older patients are often positive for HLA-DR4

• The principal susceptibility allele among white Americans and northern Europeans is HLA DRB1*0301; HLA DRB1*0401 is a secondary but independent risk factor

Clinical Findings

Symptoms and Signs

• Typically, a healthy-appearing young woman with multiple spider telangiectasias, cutaneous striae, acne, hirsutism, and hepatomegaly

• Amenorrhea may be a presenting feature

• Frequency of depression appears to be increased

• Extrahepatic features

  • Arthritis

  • Sjögren syndrome

  • Thyroiditis

  • Nephritis

  • Ulcerative colitis

  • Coombs-positive hemolytic anemia

Differential Diagnosis

• Chronic viral hepatitis

• Primary biliary cholangitis

• Primary sclerosing cholangitis

• Wilson disease

• Hemochromatosis

• Drug-induced liver disease

• α₁-Antiprotease (antitrypsin) deficiency

Diagnosis

Laboratory Tests

• The serum bilirubin is usually increased, but 20% are anicteric

• Serum aminotransferase levels may be > 1000 units/L

• Type I (classic) autoimmune hepatitis

  • ANA or smooth muscle antibodies (either or both) are usually detected in serum

  • Serum γ-globulin levels are typically elevated (up to 5–6 g/dL [0.05-0.06 g/L])

    • In this setting, the enzyme immunoassay for antibody to hepatitis C virus may be falsely positive

    • Other antibodies, including antineutrophil cytoplasmic antibodies (ANCA), may be found

• Type II

  • Seen more often in Europe in girls under age 14

  • Characterized by circulating antibodies to liver–kidney microsome type 1 (anti-LKM1)— directed against ...