Hepatitis A

Hepatitis A is a viral disease caused by the hepatotropic hepatitis A virus (HAV) and usually spreads through fecal-oral transmission. About half of all patients with hepatitis A in the US acquire the HAV during visits to countries in which HAV is endemic (tropical or subtropical regions). HAV infection can cause acute viral hepatitis, which initially manifests with prodromal symptoms (fever and malaise), followed by jaundice. The laboratory findings in hepatitis A are similar to those observed in other forms of acute viral hepatitis and include high serum transaminase levels and mixed hyperbilirubinemia. Serological detection of anti-HAV IgM antibodies confirms the diagnosis of hepatitis A. While prodromal symptoms typically resolve within a few weeks, jaundice may persist for 1–3 months. Hepatitis A is typically self-limited with no chronic sequelae, and acute liver failure rarely occurs; therefore, only supportive care is typically required. In the US, routine immunization against HAV is recommended for all children > 12 months of age. Individuals at increased risk of infection, such as travelers to areas in which HAV is endemic, as well as individuals at increased risk of severe disease, such as those with chronic liver disease, should also be immunized against HAV if they have not been previously vaccinated. The hepatitis A immunization series generally provides long-term immunity, without the need for booster doses.

• Incidence (in the US): ∼ 2,000 cases per year (50% acquired during travels abroad) ^[1]
  • Hepatitis A virus is the second most common cause of acute hepatitis in the US.
  • Hepatitis A is very common in tropical and subtropical regions.
• Age: Vaccination programs have made the disease fairly rare in children; infection is now more widespread in adults. ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: hepatitis A virus ^[2]
  • Belongs to the family of Picornaviridae and the genus Hepatovirus
  • Small (27 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA
  • Resistant to denaturation by gastric acid, heat, and chemicals, and can remain viable for months in fresh and saltwater
  • Humans are the only reservoir for the hepatitis A virus. ^[3]
• Route of transmission: fecal-oral ; ^[4]
  • Contaminated water and food (e.g., raw shellfish)
  • Risk groups: international travelers, nursing home residents, prison inmates, men who have sex with men, IV drug users.
• Infectious period: 2 weeks before to 1 week after the onset of the illness ^[3]

When it comes to viral hepatitis, vowels (A and E) are bowels (transmitted feco-orally).

HAV is not cytopathic in itself; research suggests that liver damage is caused by cellular immunity (especially CD8+ T cells). ^[2]

HAV infection in children is typically asymptomatic. The risk of symptomatic disease increases with age and coinfection (e.g., with hepatitis B).

• Incubation period: : 2–6 weeks
• Phases of acute viral hepatitis ^[2][4]
  1. Prodromal phase: 1–2 weeks
     • Right upper quadrant pain, tender hepatomegaly
     • Fever, malaise
     • Anorexia, nausea, vomiting
  2. Icteric phase: ∼ 2 weeks
     • Jaundice
     • Dark urine and pale stools
     • Pruritus
  3. Resolution of symptoms
• Potential complications: cholestasis, relapsing HAV infection, and autoimmune hepatitis
• Prognosis ^[1]
  • The mortality rate is 0.1–0.3% because few patients progress to acute liver failure.
  • Individuals affected with hepatitis A (unlike with hepatitis B and hepatitis C) do not become carriers nor do they develop chronic hepatitis.

When it comes to viral hepatitis, vowels (A and E) cause only AcutE hepatitis while Consonants (B, C, and D) may have Chronic sequelae as well.

Laboratory testing ^[5][6][7]

• Routine studies
  • ↑ Serum transaminase levels (AST, ALT)
  • AST/ALT ratio is usually < 1 ^[8]
  • ↑ Total bilirubin and urine bilirubin ^[9]
  • ↑ ALP, ↑ GGT
• Confirmatory testing
  • ↑ Anti-HAV IgM antibodies: present in patients with active infection
    • Usually detectable 5–10 days after exposure and 5–10 days before clinical symptoms develop
    • Levels peak commonly ∼ 1 month after infection.
    • May persist for up to 6 months after infection
  • ↑ Anti-HAV IgG antibodies
    • Develop during active infection and persist indefinitely after infection or vaccination
    • Production begins within 2–3 weeks of infection.
  • HAV RNA can be detected in stool and serum samples using PCR.

The presence of anti-HAV IgM antibodies or HAV RNA confirms active hepatitis A. Detection of anti-HAV IgG antibodies in the absence of anti-HAV IgM antibodies indicates immunity against HAV due to prior infection or vaccination. ^[6]

Further testing

Further diagnostic testing is not routinely necessary but may be used to rule out differential diagnoses or in fulminant hepatitis. If performed, additional tests may show the following findings if acute viral hepatitis is present:

• Liver biopsy: not routinely indicated ^[10]
  • Periportal inflammation (mononuclear cell infiltration) ^[11]
  • Hepatocyte swelling
  • Ballooning degeneration
  • Bridging necrosis
  • Councilman bodies (apoptotic hepatocytes) ^[12]
• Ultrasound ^[13]
  • Increased brightness of portal vein radicle walls
  • Decreased echogenicity of the liver

For an overview comparing the different types of viral hepatitis see “Overview of viral hepatitides.”

The differential diagnoses listed here are not exhaustive.

• Hepatitis A is generally self-limited.
• Offer supportive care. ^[5]
  • Recommend rest as needed.
  • Consider symptomatic treatment, e.g., antiemetics.
  • Inability to maintain hydration with oral fluids can be an indication for parenteral fluid therapy and hospitalization.
• Recommend alcohol avoidance.
• Use medications that are metabolized by the liver with caution (e.g., acetaminophen).
• More intensive treatment may be required in rare cases in which hepatitis A leads to acute liver failure.

Hepatitis A preexposure prophylaxis ^[6][7]

• Advise all travelers to follow primary preventive measures such as food and water safety.

Hepatitis A vaccine

See “ACIP immunization schedule” for scheduling details.

• Recommend routine active immunization for:
  • All children > 12 months of age
  • Individuals at increased risk of HAV infection, including those who:
    • Are traveling to a country in which HAV is endemic
    • Expect to be in close contact with an adoptee from a country in which HAV is endemic
    • Have a potential occupational exposure to HAV
    • Are men who have sex with men
    • Use injection or noninjection drugs
    • Have unstable housing
  • Individuals at increased risk of severe disease
    • Individuals with chronic liver disease
    • Adults and children > 12 months of age with HIV
  • Any individual requesting to be vaccinated
• Consider active immunization for:
  • Individuals in settings with people at increased risk of infection (e.g., homeless shelters, needle exchange programs, group homes)
  • Individuals at increased risk of HAV infection, including currently or recently incarcerated individuals, during outbreaks
• Two single-antigen inactivated hepatitis A vaccines and one combination hepatitis A and hepatitis B inactivated vaccine are available in the US.

Hepatitis A vaccination is considered suitable for use during pregnancy in previously unvaccinated individuals with an increased risk of infection or severe disease. ^[6]

Hepatitis A postexposure prophylaxis ^[6]

Postexposure prophylaxis is indicated for all previously unvaccinated individuals who have been in contact with an individual with serologically confirmed hepatitis A within the past two weeks. Hepatitis A is a notifiable disease.