Hepatitis A virus

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Background

Microbiology

  • Non-enveloped RNA virus within the Picornaviridae family
  • Three genotypes, I through III
  • Difficult to kill: needs higher temperatures and lower pH than other viruses, or bleach- or ammonium-based cleaners

Epidemiology

  • Fecal-oral transmission with person-to-person spread (including sex)
  • Can be transmitted by contaminated food and water, as well
  • Most often linked to travel or to household contacts
  • Rare transmission by blood transfusion

Risk Factors

  • Outbreak
  • Close contact with a hepatitis A-infected person, including household, sexual, or other
  • Travel to endemic country
  • Men who have sex with men
  • Homelessness
  • Injection drug use

Clinical Manifestations

  • Incubation period is from 15 to 50 days, with an average of 28 days
  • Children are usually asymptomatic
  • Symptoms include non-specific influenza-like illness followed eventually by bilirubinuria, pale stools, jaundice, and scleral icterus
  • May have hepatomegaly and splenomegaly, may have rash or arthralgia
  • Self-limited, usually starting to resolve by the third week of illness with full recovery often taking several months

Diagnosis

Serology

  • IgM and IgG antibodies are usually detectable by onset of symptoms
  • IgM becomes undetectable by about 6 months while IgG persist lifelong and are protective[1]
IgM IgG Interpretation
No recent infection (unless in the incubation period). No prior infection or vaccination.
+ No infection. Prior infection or vaccination.
? + Cannot rule out active infection. Prior infection or vaccination.
+ +/– Acute or recent infection. IgM positive from 2 weeks until 3-12 months. IgG positive from 8-12 weeks and remains positive for lifetime.

Prevention

Vaccination

  • Vaccination is indicated for people at increased risk of acquiring hepatitis A, or at increased risk of severe disease
    • Travellers to endemic countries
    • People with chronic liver disease
    • Men who have sex with men
    • People who use recreational drugs
    • People living in communities with outbreaks or endemic hepatitis A
    • Close contacts of children adopted from endemic countries
    • Military personnel and humanitarian relief workers
    • People receiving repeated doses of plasma-derived clotting factors
    • Laboratory workers studying hepatitis A
    • Zookeepers, veterinarians, and researchers who interact with non-human primates
  • Vaccination requires two doses spaced at least 6 months apart
  • It provides immunity for decades, and possibly for life

Coformulation with Hepatitis B Vaccine

  • Often given combined with hepatitis B vaccine (HAHB)
  • HAHB is given as three doses (for the hepatitis B component)
  • The hepatitis A component contains a full dose of hepatitis A vaccine, so a HAHB series essentially contains an extra unnecessary dose of hepatitis A vaccine

High Risk Groups Who Cannot Receive Vaccine

  • In people with contraindications or who are expected to have suboptimal response to vaccination, consider using immunoglobulin as preexposure prophylaxis
  • Groups include:
    • Infants less than 6 months of age
    • Immunocompromised people in whom the vaccine may not be as effective (though they should also still be vaccinated)
    • Anaphylaxis after previous hepatitis A vaccination or component thereof
  • Administering just before travel can confer immunity for up to 6 months of travel
  • Dose is IMIg (GamaSTAN) 0.02 mL/kg for 3 months of protection, or 0.06 mL/kg every 6 months
    • CDC recommends a dose of IMIg (GamaSTAN S/D) 0.2 mL/kg q2mo due to decreases in hepatitis A IgG among donors

Publicly Funded in Ontario

  • Only a subset of patients are publicly funded in Ontario:
    • Intravenous drug use
    • Chronic liver disease, including hepatitis B and C
    • Men who have sex with men

Post-Exposure Prophylaxis

  • Post-exposure prophylaxis is indicated for susceptible contacts including:
    • Household members and close contacts of people infected with hepatitis A
    • Contacts in group childcare centres and kindergartens
    • Co-workers and clients of infected food handlers
  • Prophylaxis is with monovalent hepatitis A vaccine
  • In people with contraindications or who are expected to have suboptimal response to vaccination, immunogloulin should be given
    • Groups include:
      • Infants less than 6 months of age
      • Immunocompromised people and people with liver disease, who should receive both vaccine and immunoglobulin
        • If they have received IVIg ≥400 mg/kg within the 3 weeks before exposure, then they do not require further immunoglobulin
      • Elderly susceptible adults age 60 years and older may also receive both
    • It should be given as soon as possible, and can be given until 14 days after last exposure
    • Dose is IMIg (GamaSTAN) 0.02 mL/kg body weight
      • CDC recommends a dose of IMIg (GamaSTAN S/D) 0.1 mL/kg body weight due to decreases in hepatitis A IgG among donors
  1. Jack T. Stapleton, Host Immune Response To Hepatitis A Virus, The Journal of Infectious Diseases, Volume 171, Issue Supplement_1, March 1995, Pages S9–S14, https://doi.org/10.1093/infdis/171.Supplement_1.S9