Hepatitis E

Infectious Agent

Infection is caused by hepatitis E virus (HEV), a single-stranded, single-serotype, RNA virus belonging to the Hepeviridae family. Four HEV genotypes are known to cause human disease. HEV genotype 3 causes hepatitis E in developed countries, whereas genotypes 1, 2, and 4 are associated with illness in developing countries. HEV genotype 1 and to some extent genotype 2 are associated with large waterborne outbreaks.


HEV genotype 1 is transmitted primarily by the fecal-oral route. In regions with poor sanitation and limited access to safe drinking water, epidemics and interepidemic occurrences of hepatitis E are largely waterborne. In developing countries transmission to fetuses and neonates by women infected during pregnancy is common. In Japan and Europe, sporadic disease can be zoonotic and foodborne, associated with eating meat and offal (including liver) of deer, boars, and pigs and is mainly caused by HEV genotype 3. In France, disease can be acquired from eating figatellu , a sausage delicacy prepared from raw pig liver. A hepatitis E outbreak on a cruise ship was associated with consumption of shellfish. Transmission from blood transfusion is rare. Rare symptomatic disease is observed in the United States, but its mode of transmission is generally unknown.


Waterborne outbreaks (which can be large, often involving hundreds to thousands of people) have occurred in South and Central Asia, tropical East Asia, Africa, and Central America. In outbreak-prone areas, interepidemic disease is sporadically encountered. Sporadic disease also occurs in regions that are not prone to outbreaks, such as the Middle East, temperate East Asia (including China), North and South America, and Europe (Map 3-6).

Map 3-6. Hepatitis E endemic countries 1
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1 Disease data adapted from: World Health Organization. The Global Prevalence of Hepatitis E Virus Infection and Susceptibility: A Systematic Review. (WHO/IVB/10.14). 2010 (Accessed Aug 13, 2016). Available from: http://apps.who.int/iris/bitstream/10665/70513/1/WHO_IVB_10.14_eng.pdf.

2 Defined as waterborne outbreaks or confirmed Hepatitis E virus infection ≥25% of sporadic non-A, non-B hepatitis.

3 Defined as confirmed Hepatitis E virus infection in <25% of sporadic non-A, non-B hepatitis.

During outbreaks of hepatitis E, clinical attack rates are highest in young adults aged 15–49 years. In outbreak-prone areas, pregnant women—whether infected sporadically or during an epidemic—are at risk of their HEV infection progressing to liver failure and death. Miscarriages and neonatal deaths are common complications of HEV infection. In areas that are not prone to outbreaks, symptomatic disease is observed most frequently in adults aged >50 years. HEV genotype 3 infection acquired by people who are immunosuppressed, particularly recipients of solid-organ allografts, may progress to chronic infection.

People living in the United States are at highest risk of HEV infection when they travel to areas where epidemics have occurred. When traveling in Japan and Europe, eating raw or inadequately cooked venison, boar meat, pig liver, pig meat, or food products derived from these is a risk factor for infection.

Clinical Presentation

The incubation period of HEV infection is 2–9 weeks (mean 6 weeks). Signs and symptoms of acute hepatitis E include jaundice, fever, loss of appetite, abdominal pain, and lethargy. Infection with HEV genotype 3, common in developed countries, is generally asymptomatic but can progress to chronic infection in rare cases, whereas genotypes 1, 2, and 4 result only in acute infection. For most people, HEV infection and disease is self-limited. Pregnant women with genotype 1, 2, or 4 infection (especially those infected during the third trimester) may present with or progress to liver failure, and their fetuses are at risk of spontaneous abortion and premature delivery. To date, there is no evidence that HEV genotype 3 is associated with severe outcome in pregnant women. People with preexisting liver disease may undergo further hepatic decompensation with HEV infection. Recipients of solid organ transplants tend to have no symptoms associated with acute and chronic HEV infection, but progressive liver injury can result when infected with HEV genotype 3.


The diagnosis of acute hepatitis E is established by detecting anti-HEV IgM in serum. Detecting HEV RNA in serum or stools further confirms the serologic diagnosis but is seldom required. Longer-term, serial detection of HEV RNA in serum or stools, regardless of the HEV antibody serostatus, suggests chronic HEV infection. No diagnostic test for HEV has been approved by the Food and Drug Administration.


Treatment is supportive. Oral ribavirin has been used to treat chronic hepatitis E in solid-organ transplant recipients.


No vaccine is available for prevention. Travelers should avoid drinking unboiled or unchlorinated water and beverages that contain unboiled water or ice. Travelers should eat only thoroughly cooked food, including seafood, meat, offal, and products derived from these (see Chapter 2, Food & Water Precautions).

CDC website: www.cdc.gov/hepatitis/HEV


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Eyasu H. Teshale