• Clinical science

Hepatitis A

Abstract

Hepatitis A infection is caused by the hepatotropic hepatitis A virus (HAV) and is usually transmitted via the fecal-oral route. About half of all cases of HAV infection that occur in the US are acquired during visits to countries that are endemic for HAV (e.g., tropical or subtropical regions). HAV infection results in acute hepatitis with a clinical course characterized by prodromal symptoms of fever and malaise, followed by jaundice. As in any other case of acute viral hepatitis, high levels of serum transaminase and mixed hyperbilirubinemia are observed. Serological detection of anti-HAV IgM, which is elevated during an acute infection, confirms the diagnosis. While prodromal symptoms resolve within a few weeks, jaundice usually resolves within 1–3 months. No chronic sequelae occur and acute hepatic failure occurs only in very rare cases. Therefore, supportive care is usually the only treatment required. As of 2006, routine immunization against hepatitis A is recommended for all children older than 12 months. Certain high-risk groups, such as tourists to areas where HAV is endemic, should also be immunized against HAV if they have not been vaccinated in the past.

An important differential diagnosis is another feco-orally transmitted viral infection: hepatitis E (HEV). The clinical presentation of HEV is almost identical to that of HAV, with the exception that pregnant women are at a high risk of developing acute liver failure. Serological tests help to distinguish HEV from HAV.

Epidemiology

  • Hepatitis A infection is the second most common cause of acute hepatitis in the US.
  • Hepatitis A is very common in tropical and subtropical regions.
  • Incidence: (in the US): 2,000 cases per year (50% acquired during travels abroad)
  • Average age of infected persons: vaccination programs have made the disease fairly rare in children; infection is now more widespread in adults.

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Pathogen: hepatitis A virus
    • Belongs to the family of Picornaviridae and the genus Hepatoviridae; . It is a small (27 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA
    • Humans are the only reservoir for the hepatitis A virus.
    • Extremely resistant to denaturation by heat and chemicals and can remain viable for many years
  • Route of transmission: fecal-oral
    • Contaminated food, e.g., raw shellfish
    • Risk groups: children, employees of day care centers, convicts, men who have sex with men
  • Infectious period: 2 weeks before to 1 week after the onset of the illness

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

References:[4][1][2][5][6]

Pathophysiology

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

References:[1][2][2][6]

Clinical features

  • Incubation period: 2–6 weeks
  • HAV infection in children is typically asymptomatic. The risk of symptomatic infection increases with age and coinfection (e.g., with hepatitis B).
  • Acute viral hepatitis: three phases
    1. Prodromal phase: ∼ 1–2 weeks
      • Fever, malaise
      • Anorexia, nausea, vomiting
      • Right upper quadrant pain and tender hepatomegaly
    2. Icteric phase: ∼ 2 weeks
    3. Resolution of symptoms
  • Potential complications: cholestasis, relapsing HAV infection
  • The mortality rate is 0.1–0.3% because few patients progress to acute liver failure.
  • Patients do not become carriers nor develop chronic hepatitis (unlike in hepatitis B and C).

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!

References:[4][1][2][3][6]

Diagnostics

Positive IgG values indicate immunity against HAV due to prior infection or vaccination!

References:[4][1][7][2][8][3][6]

Differential diagnoses

For an overview comparing the different types of viral hepatitis: see differential diagnosis of viral hepatitis.

Hepatitis E

  • Pathogen: hepatitis E virus (HEV)
    • The hepatitis E virus, which belongs to the family of Hepeviridae and the genus Orthohepeviridae; , is a small (34 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA.
    • HEV genotypes 1 and 2 are found only in humans, but genotypes 3 and 4 are zoonotic diseases with reservoirs in both humans and animals (e.g., pigs, monkeys, and dogs).
  • Epidemiology: HEV is not common in the US.
  • Route of transmission: fecal-oral
  • Pathophysiology: the degree of hepatic injury is usually mild and the patient may present with clinical features of acute hepatitis
  • Clinical features:
    • Incubation period: 2–8 weeks
    • Clinical features are similar to those of hepatitis A (see “Symptoms/clinical findings” above).
    • In the majority of cases, the disease is self-limiting with complete recovery.
    • Fulminant hepatitis among pregnant women
    • Patients do not become carriers nor develop chronic hepatitis (unlike in hepatitis B and C). However, chronic hepatitis E infection has been reported in immunosuppressed individuals (e.g., following transplantation, or in pateints with AIDS).
  • Diagnostics
    • Laboratory findings are the same as in hepatitis A.
    • Confirmatory test
      • Anti-HEV IgM: active infection
      • Anti-HEV IgG: past infection
      • HEV RNA can be detected by PCR in stool and serum samples during the prodromal phase and up to 3 months after the onset of symptoms.
  • Treatment: supportive care
    • No specific antiviral therapy
  • Prevention: no vaccine available

Fulminant hepatitis due to HEV is relatively common among pregnant women (occurring in up to 20% of cases) and is life-threatening for both the mother and fetus!

References:[4][1][2][5][3][6][9][10][11][12]

The differential diagnoses listed here are not exhaustive.

Treatment

  • Disease is self-limitingsupportive care.

References:[5]

Prevention

Pre-exposure prophylaxis

  • Travelers should be advised to follow primary preventive measures such as hand-washing and following proper food and water safety
  • Routine active immunization is now recommended for all children over 12 months consisting of a first IM dose of hepatitis A vaccine followed by a booster dose after 6 months (see also “Immunization schedule”)
  • Active immunization is also recommended for certain high-risk groups who have not been immunized in the past:

Post-exposure prophylaxis

Post-exposure prophylaxis; is indicated for all previously unvaccinated individuals; who have been exposed to a serologically confirmed case of HAV infection. In order to be effective, post-exposure prophylaxis should be administered within two weeks of exposure.

  • Healthy individuals aged 1–40 years: active immunization with hepatitis A vaccine
  • Infants, individuals older than 40 years, patients with chronic liver disease and/or immunosuppression: passive immunization with anti-HAV immunoglobulins (0.20 mL/kg)
  • Hepatitis A is a notifiable disease.

References:[4][6][13][14]