Summary
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.
Hepatitis E, caused by the hepatitis E virus (HEV), which is also spread through fecal-oral transmission, is an important differential diagnosis. The clinical features of hepatitis E are almost identical to those of hepatitis A, with the exception that pregnant women are at a higher risk of developing acute liver failure with hepatitis E. Serological tests help to distinguish hepatitis E from hepatitis A.
Epidemiology
- Incidence (in the US): ∼ 2,000 cases per year (50% acquired during travels abroad) [1]
- 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.
Etiology
-
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).
Pathophysiology
HAV is not cytopathic in itself; research suggests that liver damage is caused by cellular immunity (especially CD8+ T cells). [2]
Clinical features
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]
-
Prodromal phase: 1–2 weeks
- Right upper quadrant pain, tender hepatomegaly
- Fever, malaise
- Anorexia, nausea, vomiting
- Icteric phase: ∼ 2 weeks
- Resolution of symptoms
-
Prodromal phase: 1–2 weeks
- 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.
Diagnostics
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.
-
↑ Anti-HAV IgM antibodies: present in patients with active infection
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
Differential diagnoses
For an overview comparing the different types of viral hepatitis see “Differential diagnosis of viral hepatitis.”
Hepatitis E [14][15]
-
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). [16]
- Epidemiology
- 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). [17]
-
Diagnostics [2]
- Laboratory findings are the same as in hepatitis A.
-
Confirmatory test
- Anti-HEV IgM antibodies: active infection
- Anti-HEV IgG antibodies: 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.
Treatment
- 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.
Prevention
Hepatitis A preexposure prophylaxis [6][7]
- Advise all travelers to follow primary preventive measures such as food and water safety.
Hepatitis A vaccine
-
Recommend routine active immunization for:
- All children > 12 months of age (see “Immunization schedule”)
-
Individuals at increased risk of 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
- 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.
| Recommended regimens for hepatitis A postexposure prophylaxis | |
|---|---|
| Type of postexposure prophylaxis | Indications |
| Active immunization |
|
| Passive immunization with immune globulin |
|
| Both active and passive immunization |
|