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The classic presentation is the gradual onset of malaise, nausea, anorexia, and right upper quadrant pain, followed by jaundice.


  1. Prevalence: Accounts for approximately half of cases of viral hepatitis in the United States.

  2. Clinical manifestations

    1. Symptoms develop in 70–80% of adults, compared with < 30% of children under the age of 6.

    2. Average incubation period is 28 days (range 15–50 days), followed by prodromal symptoms of fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper pain; about 1 week later, jaundice appears.

    3. 70% of patients have jaundice, and 80% have hepatomegaly.

    4. Other physical findings include splenomegaly, cervical lymphadenopathy, rash, arthritis, and leukocytoclastic vasculitis.

    5. Uncommon extrahepatic manifestations include optic neuritis, transverse myelitis, thrombocytopenia, and aplastic anemia.

  3. Transmission

    1. Fecal-oral transmission, either sporadically or in an epidemic form

      1. Contaminated water, shellfish, frozen strawberries, etc.

      2. Contamination from infected restaurant worker

      3. No specific exposure history in 55% of cases

    2. No maternal-fetal transmission

  4. Clinical course

    1. Generally self-limited, with rare cases of fulminant hepatic failure (0.015–0.5% of patients with hepatitis A)

      1. Fulminant course is more common in patients with underlying hepatitis C or other chronic liver diseases.

      2. 1.1% fatality rate in adults > age 40

    2. 85% of patients fully recover in 3 months, and nearly 100% by 6 months

    3. Transaminases normalize more rapidly than serum bilirubin.

  5. Prevention

    1. Vaccination is available for preexposure prophylaxis.

      1. Immunity develops within 4 weeks in 90% of patients and within 26 weeks in 100% of patients.

      2. A second dose given 6–12 months later provides persistent immunity.

    2. Can use immune serum globulin with vaccination for postexposure prophylaxis.

      1. For otherwise healthy patients between ages 12 months and 40 years, only vaccination is recommended; immune serum globulin can still be considered.

      2. For patients < 12 months, > 40 years, or any age who are immunocompromised, such as those with chronic liver disease, immune serum globulin should be administered.

      3. Immune globulin is 69–89% effective in preventing symptomatic illness when used within 2 weeks of exposure.

      4. A randomized trial comparing vaccination with immune globulin given within 14 days of exposure found that hepatitis A developed in 4.4% of vaccine recipients and 3.3% of immune globulin recipients (relative risk = 1.35 (95% confidence interval [CI], 0.70 to 2.67).


  1. Liver biochemical tests

    1. ALT and AST are generally over 1000 units/L, and may be as high as 10,000 units/L; ALT is generally > AST.

    2. Bilirubin is commonly > 10 mg/dL.

    3. Alkaline phosphatase is usually modestly elevated.

  2. Antibody tests (Figure 26-3)

    1. Serum IgM anti-HAV detects acute illness, being positive even before the onset of symptoms and remaining positive for 4–6 months.

    2. LR+ 99; LR−, 0.01

    3. Serum IgG anti-HAV appears in the convalescent phase of the disease and remains positive for decades.

Figure 26-3.

Natural history of hepatitis A symptoms and antibodies. ALT, alanine aminotransferase; HAV, hepatitis A virus. (Reproduced with permission from Frauci AS, Kasper DL, Braunwald E, et al: Harrison’s Principles ...

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