Description

Hepatitis A infections are caused by the hepatitis A virus (HAV), a member of the Hepatovirus genus. This virus is one of the world’s most common infections and primarily involves the liver. HAV is one of several types of hepatitis viruses that can lead to liver injury. However, compared to the other hepatitis viruses, HAV has distinct features that set it apart.

Epidemiology

Incidence

• 1.4 million cases globally each year
• Since the release of the HAV vaccine in 1995, the incidence of HAV in the United States decreased by 95% from 1996 to 2011.
• Regional outbreaks have contributed to the increasing number of reported cases in the United States (1).
• 12,474 cases were documented in 2018 in the United States (2).
• Incidence was approximately 4.0/100,000 in 2018 in the United States (2).
• No difference in infection rates based on sex
• As many as 1/2 of current HAV infections in the United States are acquired during travel to endemic countries.
• Incubation period of 28 days (range 15 to 50 days)

Prevalence
Serologic evidence of prior HAV infection is present in approximately 1/3 of the U.S. population. Anti-HAV prevalence relates to age, ranging from 9% in children ages 6 to 11 years to 75% of those >70 years.

Pediatric Considerations

• Often, milder or asymptomatic in children; severity increases with age.
• Infections asymptomatic in 70% of children <6 years
• >75% of 13- to 17-year-olds in the United States are vaccinated.

Pregnancy Considerations

• Increased risk of complications including preterm labor, premature rupture of membranes, antepartum hemorrhage, and placental abruption
• Vertical transmission has been reported; fecal–oral transmission during birth is possible.
• Breastfeeding is not contraindicated.

Etiology and Pathophysiology

• HAV is a single-stranded linear RNA enterovirus of the Picornaviridae family. Infection is limited to hepatocytes and macrophages.
• HAV is excreted into the bile and then stool, providing major route of spread. Primary transmission is fecal–oral. Can also transmit through sexual intercourse (particularly anal-oral contact) and intravenous drug use. Humans are the only natural host.
• Incubation is 2 to 6 weeks (mean 4 weeks). Greatest infectivity is the 2 weeks before and 1 week after onset of clinical illness.
• Infection occurs primarily after consuming food or water contaminated with HAV or via direct contact.
• Virus is stable in water and on surfaces but is easily killed with high heat or cleaning agents.
• Shellfish (clams and oysters) may be contaminated if harvested from waters contaminated with HAV.
• Blood-borne transmission is rare.
• HAV is not a chronic disease.

Genetics
Autoimmune hepatitis is rarely associated with HLA class II DR3 and DR4 after infection with HAV.

Risk Factors

• Person-to-person contact:
  • Intimate exposure, particularly among men who have sex with men
  • Residential institutional transmission
  • Employment in health care
  • Household exposure
  • Child care centers, schools
• Contaminated food or water contact:
  • Travel to developing countries accounts for >50% of cases in North America and Europe.
  • Consumption of raw/undercooked shellfish, vegetables, or other foods
  • Consumption of improperly handled food
• Other modes of transmission:
  • Injection of illicit drugs
  • Clotting factor disorders, such as hemophilia
  • Blood exposure or transfusion (rare)
  • No identifiable risk factor in 50%

General Prevention

• Proper sanitation and personal hygiene (hand washing), especially for food handlers, health care, and daycare workers
• Active immunization through HAV vaccines:
  • Havrix and Vaqta—inactivated vaccine
  • Twinrix—combination HAV and HBV
• Vaccine provides protection for 20+ years (2).
• Vaccine is recommended for (3)[A]:
  • All children aged 12 to 23 months, with catch-up administration until 18 years old
  • All travelers to countries with high endemic rate of hepatitis A (parts of Africa, Central and South America, and South and Southeast Asia)
  • Men who have sex with men
  • Individuals using injection and noninjection drugs
  • Individuals with occupational risks
  • Pregnant women, if risk of infection or severe outcomes is present
  • All individuals ≥1 year of age with HIV
  • Chronic liver disease (including pre– and post–liver transplant patients)
  • Household members and close contacts of children adopted from countries with a high HAV prevalence (prior to arrival)
  • Individuals experiencing homelessness or unstable housing
  • Unvaccinated individuals exposed during an outbreak
• Routine vaccination is no longer routinely recommended for individuals who receive blood products for treatment clotting disorders (3)[A].
• Do not delay vaccination in individuals with HIV until CD4 count surpasses a certain threshold (3)[A].
  • Vaccination response may be reduced in individuals with HIV. Postvaccination serologic testing should be conducted ≥1 month after HAV series.
  • Individuals with HIV who do not respond should consider revaccination and Ig prophylaxis.
• HAV is not killed by freezing; HAV is killed by:
  • Heating to >185°F for 60 seconds
  • Chlorine, iodine

Commonly Associated Conditions

HAV can sometimes be associated with more rare extrahepatic manifestations such as (4):

• Glomerulonephritis, cryoglobulinemia, optic neuritis
• Myocarditis, pericardial effusion, Guillain-Barré syndrome, pancreatitis
• Pneumonitis, pleural effusion
• Thrombocytopenia, aplastic anemia, or red cell aplasia, leukocytoclastic vasculitis