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Confirmation of reactive hepatitis E virus IgM antibody screening test results for the diagnosis of acute or recent (<6 months) hepatitis E infection
See Testing Algorithm for the Diagnosis of Hepatitis E in Special Instructions.
Hepatitis E virus (HEV) causes an acute, usually self-limited infection. This small, nonenveloped RNA virus is from animal reservoirs (eg, hogs) and is transmitted to humans via the fecal-oral route. HEV is endemic in Southeast and Central Asia, with several outbreaks observed in the Middle East, northern and western parts of Africa, and Mexico. In developed countries, HEV infection occurs mainly in persons who have traveled to disease-endemic areas. Transmission of HEV may also occur parenterally, and direct person-to-person transmission is rare. Clinically severe cases occur in young to middle-aged adults. Unusually high mortality (approximately 20%) occurs in patients infected during the third trimester of pregnancy. Although there is no carrier state associated with HEV, immunocompromised patients may have prolonged periods (eg, months) of viremia and virus shedding in the stool.
In immunocompetent patients, viremia and virus shedding in the stool occur in the pre-icteric phase, lasting up to 10 days into the clinical phase. After an incubation period ranging from 15 to 60 days, HEV-infected patients develop symptoms of hepatitis with appearance of anti-HEV IgM antibody in serum, followed by detectable anti-HEV IgG within a few days. Anti-HEV IgM may remain detectable up to 6 months after onset of symptoms, while anti-HEV IgG usually persists for many years after infection. Anti-HEV IgM is the serologic marker of choice for diagnosis of acute HEV infection.
Positive predictive value of a given diagnostic laboratory test is dependent on the prevalence rate of the disease for which the test is being used. Screening tests for detection of diseases with low prevalence rates, such as acute hepatitis E, will have low positive predictive values (ie, relatively high rates of false-positive test results), despite having high specificity rates for such tests. Therefore, an HEV IgM antibody confirmatory test will be helpful and necessary to determine the true infection status of patients with reactive HEV IgM antibody screening test results.
Positive results confirm the presence of acute or recent (in the preceding 6 months) hepatitis E infection.
Negative results indicate absence of acute or recent hepatitis E infection.
Indeterminate results may be seen in: 1) acute hepatitis E infection with rising level of anti-hepatitis E virus (HEV) IgM; 2) recent hepatitis E infection with declining level of anti-HEV IgM; 3) acute hepatitis E infection due to HEV genotype 2 strains; or 4) cross-reactivity with nonspecific antibodies (ie, false-positive results). Repeat testing of serum for anti-HEV IgM and anti-HEV IgG in 4 to 6 weeks is recommended to determine the definitive HEV infection status.
Unreadable results indicate the presence of unusually strong, nonspecific reactivity of the assay strip background that obscures proper reading of the bands. Such findings are usually due to nonspecific binding of non-hepatitis E IgM antibodies in patient's serum to the HEVM antigens present on the assay strip. Repeat testing with anti-HEV IgM screen and anti-HEV IgG in 1 to 2 weeks is recommended.
A negative test result does not exclude the presence of recent hepatitis E infection, especially in immunocompromised patients. Repeat testing of serum for anti-hepatitis E virus (HEV) IgM in 1 to 2 weeks may be necessary for diagnosis of acute or recent hepatitis E infection.
Performance characteristics of this assay have not been established for serum specimens that are icteric, lipemic, hemolyzed or contain particulate matter.
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