Hepatitis A

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 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 caused by the hepatitis E virus (HEV). The clinical presentation of hepatitis E is almost identical to that of hepatitis A, with the exception that pregnant women are at a high risk of developing acute liver failure. Serological tests help to distinguish HEV from HAV.

• Incidence (in the US): ∼ 2,000 cases per year (50% acquired during travels abroad) ^[1]
  • 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.
• 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 Hepatoviridae
  • 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: nursing home residents, international travelers, 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 findings ^[1][4]
  • ↑ Serum transaminases (AST, ALT)
  • Mixed hyperbilirubinemia ^[5]
  • Possibly ↑ ALP, ↑ γ-GT
  • Atypical lymphocytosis ^[6]
  • Urine analysis: ↑ urine bilirubin, ↑ urobilinogen
• Confirmatory test
  • ↑ Anti-HAV IgM: active infection ^[7][8]
    • Anti-HAV IgM antibody levels begin to increase 1 week after the onset of symptoms and peak at around 4 weeks, after which they decrease again.
    • Anti-HAV IgM can be found in serum 3–6 months after infection.
  • ↑ Anti-HAV IgG: past infection or vaccination
  • HAV RNA can be detected by PCR in stool and serum samples.
• Liver biopsy (not normally necessary) ^[2]
  • Periportal inflammation (monocyte infiltration)
  • Hepatocyte swelling
  • Ballooning degeneration
  • Bridging necrosis
  • Councilman bodies (apoptotic hepatocytes)

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

For an overview comparing the different types of viral hepatitis see “Differential diagnosis of viral hepatitis”.

Hepatitis E ^[9][10]

• 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). ^[11]
• Epidemiology
  • Uncommon in the US
  • An important cause of endemic viral hepatitis in developing countries and equatorial regions (e.g., India, western and northern Africa, Middle East, and Mexico)
• Route of transmission: fecal-oral (especially via contaminated water, food, or sources)
• Pathophysiology: The degree of hepatic injury is usually mild and the patient may present with clinical features of acute hepatitis.
• Clinical features: similar to those of hepatitis A (see “Clinical features” above). ^[2]
  • Incubation period: 2–8 weeks
  • In the majority of cases, the disease is self-limiting with complete recovery.
  • Fulminant hepatitis in pregnant women (high risk of mortality for both mother and fetus)
  • Affected individuals do not become carriers nor do they develop chronic hepatitis (unlike in hepatitis B and hepatitis C). ^[12]
• Diagnostics ^[2]
  • 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.
  • Liver biopsy (not normally necessary): patchy necrosis
• Treatment: supportive care
• Prevention: no vaccine available

Women who are Expecting are FULly aware of the risks: pregnant women with hepatitis E can develop FULminant hepatitis.

A fulminant course is relatively common in pregnant women with HEV infection (occurring in up to 20% of cases) and is life-threatening for both the mother and fetus.

The differential diagnoses listed here are not exhaustive.

Disease is self-limiting; only supportive care is required.

Hepatitis A pre-exposure prophylaxis ^[3][13]

• 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:
  • Travelers to foreign countries where HAV is endemic.
  • Men who have sex with men
  • Patients with chronic liver disease

Hepatitis A post-exposure prophylaxis ^[3][4]

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
• Hepatitis A is a notifiable disease.