Hepatitis A virus

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

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