What is the best test for a patient suspected of having hepatitis A (hepatitis A virus), particularly those with a history of travel to endemic areas, men who have sex with men, or those with a history of liver disease or immunosuppression?

Hepatitis A Testing

The best test for diagnosing acute hepatitis A is anti-HAV IgM antibody, which should be ordered as part of a first-line comprehensive viral hepatitis panel that includes hepatitis A, B, C, and E simultaneously at initial presentation. 1, 2

Recommended Testing Approach

First-Line Serologic Panel

• Order anti-HAV IgM antibody as the specific diagnostic test for acute hepatitis A infection 3, 1
• Test simultaneously with hepatitis B, C, and E at initial presentation—do not wait for sequential testing 1, 2
• Anti-HAV IgM appears within days of symptom onset, reaches maximum titers within 1-3 weeks, and typically remains detectable for 3-6 months 4, 5

Performance Characteristics

• Anti-HAV IgM has >99% sensitivity and >99% specificity for diagnosing acute hepatitis A 4
• The test shows no interference from rheumatoid factor and no cross-reactivity with other hepatitis viruses 5
• Maximum IgM titers (1:6,400 to ≥1:51,200) occur during the first 30 days after illness onset 4

Critical Diagnostic Pitfall: The Window Period

Approximately 10.9% of patients with acute hepatitis A will have negative anti-HAV IgM at initial presentation due to testing too early in the disease course 6. These patients typically present with:

• Shorter time from symptom onset to testing
• Higher rate of fever
• Lower ALT and bilirubin levels compared to IgM-positive patients 6

If clinical suspicion remains high despite negative initial serology, repeat anti-HAV IgM testing within 1-2 weeks, particularly in patients with fever, early-phase hepatitis features, and high cutoff index (COI) values 6

High-Risk Populations Requiring Testing

Test for hepatitis A in patients with:

• Travel history to endemic areas (Asia, Africa, Central/South America) 3
• Men who have sex with men 3
• Injection or non-injection drug use 3
• Close contact with international adoptees 3
• Persons experiencing homelessness 3
• Chronic liver disease (including hepatitis B or C co-infection) 3
• Immunosuppression or HIV infection 3

Additional Considerations

Supplemental Testing

• Anti-HAV total or IgG antibody can be used to assess immunity status for vaccination decisions, but is not useful for diagnosing acute infection 3
• IgG avidity testing can distinguish acute infection (low avidity, AI <50%) from immune reactivation or false-positive IgM (high avidity, AI >70%), particularly in elderly patients 7
• Serum IgA anti-HAV remains detectable for 6-24 months and can help differentiate protracted hepatitis A from other causes in patients with prolonged symptoms 8

Clinical Context

• Always test for hepatitis A as part of the initial viral hepatitis workup, not as second-line testing after other viruses are excluded 1, 2
• In pregnant women with acute liver failure, also test for hepatitis E, which has 56% mortality in this population 3
• Consider hepatitis A vaccination for susceptible individuals in high-risk groups after diagnosis is established 3