How should hepatitis A immunoglobulin M (IgM) and immunoglobulin G (IgG) serology be interpreted and what are the appropriate treatment and prophylaxis recommendations for acute infection, established immunity, and post‑exposure or pre‑travel protection?

Hepatitis A Antibody Interpretation and Management

Serologic Interpretation

IgM anti-HAV indicates acute or recent hepatitis A infection, typically appearing at symptom onset and persisting for 60-120 days (though occasionally up to 200+ days), while IgG anti-HAV indicates past infection or vaccination and confers lifelong immunity. 1, 2

IgM Anti-HAV (Acute Infection Marker)

• Positive IgM = acute or recent HAV infection (within past 6 months typically) 1, 2
• IgM appears at symptom onset and peaks during acute illness 2
• Most patients become IgM-negative by 120 days, but 13.5% remain positive beyond 200 days 1
• Critical caveat: 10.9% of acute hepatitis A patients test IgM-negative initially due to a window period—repeat testing in 5-7 days if clinical suspicion is high 3
• False-positive IgM can occur from polyclonal immune activation in other liver diseases, particularly in older patients without acute hepatitis 4, 5

IgG Anti-HAV (Immunity Marker)

• Positive IgG alone (without IgM) = past infection or successful vaccination, indicating immunity 6, 7
• IgG avidity testing can distinguish acute infection (low avidity <50%) from past infection (high avidity >70%) when IgM interpretation is unclear 4
• No booster doses needed—immunity is lifelong 7

Postexposure Prophylaxis (Within 14 Days of Exposure)

For healthy persons aged 12 months to 40 years, administer hepatitis A vaccine alone (single dose) as soon as possible after exposure. 8

Age-Based Algorithm

• <12 months: IG only (0.1 mL/kg) 8
• 12 months-40 years (healthy): Hepatitis A vaccine alone (1 dose) 8
• >40 years (healthy): Hepatitis A vaccine (1 dose) + consider IG (0.1 mL/kg) based on provider risk assessment 8
• ≥12 months with immunocompromise or chronic liver disease: Both vaccine AND IG (0.1 mL/kg) simultaneously at different anatomic sites 8, 6
• Vaccine contraindicated (anaphylaxis history): IG only (0.1 mL/kg) 8

Key Implementation Points

• Prophylaxis must be given within 14 days of exposure; efficacy beyond 2 weeks is unproven 8
• Complete the 2-dose vaccine series (second dose at 6+ months) for long-term immunity, though the second dose is not required for immediate PEP 8
• Serologic confirmation of the index case with IgM anti-HAV is recommended before treating contacts 8
• Do NOT screen contacts for immunity before administering prophylaxis—this causes harmful delays 8

Pre-Travel Prophylaxis

For healthy travelers aged 12 months to 40 years, administer one dose of hepatitis A vaccine as soon as travel is considered; no immune globulin is needed. 8, 6, 7

Travel-Based Algorithm

• <6 months: IG only (0.1 mL/kg for ≤1 month travel; 0.2 mL/kg for ≤2 months) 8
• 6-11 months: Hepatitis A vaccine (1 dose)—this dose does NOT count toward the routine 2-dose series starting at 12 months 8, 6
• 12 months-40 years (healthy): Hepatitis A vaccine alone (1 dose) 8, 6, 7
• >40 years (healthy): Hepatitis A vaccine (1 dose) + may add IG (0.1-0.2 mL/kg) based on provider risk assessment 8, 7
• All ages (immunocompromised): Hepatitis A vaccine (1 dose) + IG (0.1-0.2 mL/kg) 8, 6

Special Travel Considerations

• Previously vaccinated adults in their late 30s-40s do NOT need booster doses before travel—immunity is lifelong 7
• If vaccination records are unavailable, serologic testing for anti-HAV IgG can confirm immunity, but lack of documentation should not delay travel 7
• Revaccination of previously immune individuals is safe 7

Common Pitfalls and Caveats

Diagnostic Pitfalls

• Window period: Up to 11% of acute hepatitis A cases are initially IgM-negative; repeat testing if clinical suspicion remains high, especially with fever, early presentation, and high cutoff index values 3
• False positives: IgM can persist for months or represent immune reactivation rather than acute infection, particularly in older patients with chronic liver disease 1, 4, 5
• Overuse: IgM testing is frequently ordered inappropriately in patients without acute hepatitis; restrict testing to those with clinical acute hepatitis 5

Prophylaxis Pitfalls

• IG interference: Do NOT administer MMR vaccine for at least 3 months after IG administration 8
• Combination vaccine: Do NOT use combination hepatitis A/B vaccine for postexposure prophylaxis—it contains half the HAV antigen of single-antigen vaccine 8
• Timing: Efficacy drops precipitously after 14 days; act immediately 8

High-Risk Groups Requiring Both Vaccine and IG

• Immunocompromised patients (any age ≥12 months) 8, 6
• Chronic liver disease patients (any age ≥12 months) 8, 6
• Adults >40 years with high-risk exposures (household contact, sexual contact) 8