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Hepatitis E Virus

Hepatitis E virus (HEV) is a non-enveloped RNA virus that is endemic throughout Central and Southeast Asia, India, the Middle East, North Africa, and Mexico. In these countries, HEV is a common cause of large outbreaks of acute hepatitis. Most infections are caused by HEV genotypes 1 and 2. HEV is transmitted enterically by contaminated water or food. The mean incubation period is 40 days.

HEV hepatitis is uncommon in the United States, but two studies have reported that 7.7% and 18.8% of the population has detectable IgG antibodies to HEV. In a 2016 study of United States blood donors, 2 out of 18,829 had detectable hepatitis E RNA in their bloodstream. One donor had unquantifiable viremia, and the other donor had a hepatitis E viral load of 14 IU/mL.

In North America, HEV has traditionally been associated with travel to an endemic country, but more recently has been recognized as a zoonotic pathogen. Most cases have involved HEV genotype 3 and less often genotype 4. The latter genotype has been identified in pigs and other livestock. Human cases have been associated with consumption of raw and undercooked pork, game and shellfish. Contact with farm animals may also be a risk factor.

Acute hepatitis is generally self-limited, but progression to chronic hepatitis and cirrhosis has been reported in immunosuppressed transplant recipients and patients receiving chemotherapy. The risk of acute liver failure is increased in patients with underlying chronic liver disease. A high mortality rate (15 to 25%) occurs in women infected during the third trimester of pregnancy.

A few cases of transfusion transmission of HEV virus have been reported, mostly due to genotype 3. An English study reported that a viral load less than 2.6 log IU/mL does not cause HEV infection.

Anti-HEV IgM antibody is the recommended test for diagnosis of acute HEV infection.HEV IgM is usually detectable by 4 weeks after infection in immunocompetent patients but may not be detectable until after 6 months in immunosuppressed patients. 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. A negative test does not necessarily exclude the diagnosis, especially in immunocompromised patients. In cases with high clinical suspicion and negative anti-HEV IgM result, repeat testing in 2 to 4 weeks is recommended.

Measurement of HEV RNA by PCR can also be used to confirm suspicious cases with negative serology. HEV RNA is usually detectable in the plasma of all infected individuals by 3 weeks after infection and becomes undetectable by 7 weeks in immunocompetent individuals. HEV RNA may persist more than 3 months after infection in immunocompromised patients. HEV RNA PCR can also be used to monitor response to ribavirin therapy. The limit of detect is 10 IU/mL.

Specimen requirement for HEV serology and PCR is a red top tube of blood. Reference value for HEV IgM is negative. Reference value for PCR is undetected.


Ditah I, et al. Current epidemiology of hepatitis E virus infection in the United States. Hepatology 2014;60:815-22.

Hewitt PE, et al. Hepatitis E vlurs in blood components: a prevalence and transmission study in southeast England. Lancet 2014;384:1766-73.

Petrik J. et al. Hepatitis E. Vox Sang 2016;110:93-130.

Stramer SL, Moritz ED, Foster GA. Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors. Transfusion 2016;56:481-8.

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