Hepatitis A laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Hepatitis A cannot be differentiated from other types of viral hepatitis on the basis of clinical or epidemiologic features alone. Laboratory tests are required for its diagnosis. These include: serologic tests, showing elevated IgM anti-HAV in the acute phase (gold standard), and an elevated IgG anti-HAV, which remains elevated for the person's lifetime; HAV RNA detection and sequencing; and elevated direct bilirubin and liver enzymes, such as aminotransferase and alkaline phosphatase. Liver biopsy has a minimal role in the diagnosis of HAV infection, being used in cases where the diagnosis is unclear or there is suspicion of relapse.

Laboratory Findings

Serologic Tests

Serologic testing to detect immunoglobulin M (IgM) antibody to the capsid proteins of HAV (IgM anti-HAV) is required to confirm the diagnosis of acute HAV infection.

• Immunoglobulin M (IgM) anti-HAV:

• Gold standard for the detection of acute illness
• In most persons, it becomes detectable 5-10 days before the onset of symptoms and can persist for up to 6 months after infection
• Presence of serum IgM anti-HAV antibodies in asymptomatic adults does not indicate acute infection. It may occur in the following cases:

• Previous HAV infection with prolonged presence of IgM anti-HAV
• False-positive result
• Asymptomatic infection (more common in children)

• Immunoglobulin G (IgG) anti-HAV:

• Appears early in the course of infection
• Remains detectable for the person's lifetime, conferring protection against reinfection
• Confers lifelong protection against the disease

Two serologic tests are licensed for the detection of antibodies to HAV:

• IgM anti-HAV
• Total anti-HAV (IgM and IgG anti-HAV)

In the majority of patients, IgM anti-HAV declines to undetectable levels less than 6 months after infection. However, persons who test positive for IgM anti-HAV, more than 1 year after infection have been reported, as have likely false-positive tests in persons without evidence of recent HAV infection.

Total anti-HAV testing is used in epidemiologic studies to measure the prevalence of previous infection or by clinicians to determine whether a person with an indication for pre-exposure prophylaxis is already immune.

Sensitive tests for immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-HAV in saliva have been developed but are not licensed in the United States.

Electron Microscopy

• HAV RNA can be detected in the blood and stools of the majority of persons during the acute phase of infection by using nucleic acid amplification methods.
• Nucleic acid sequencing has been used to determine the relatedness of HAV isolates for epidemiologic investigations. However, only a limited number of research laboratories have the capacity to use these methods, which makes them not commonly used in the diagnosis of HAV infection.

Liver Function Tests

Liver enzymes such as aminotransferase and alkaline phosphatase, along with direct bilirubin are commonly elevated among patients with Hepatitis A:

• The serum levels of alanine aminotransferase (ALT) are usually higher than aspartate aminotransferase (AST)
• Bilirubin levels tends to increase after the elevation of serum aminotransferase

Other Laboratory Findings

• Acute phase reactants, such as CRP and erythrocyte sedimentation rate (ESR), are commonly elevated in hepatitis A.

Serum IgG, IgM and ALT following Hepatitis A virus infection

Liver Biopsy

The role of a liver biopsy is minimal in the diagnosis of hepatitis A. It may be used in cases involving chronic relapsing hepatitis A or when the diagnosis is unclear.