Infection is caused by hepatitis E virus (HEV), a single-stranded, single-serotype, RNA virus belonging to the Hepeviridae family. Five HEV genotypes are known to cause human disease. HEV genotype 3 causes hepatitis E in developed countries, whereas genotypes 1, 2, 4, and 7 are associated with illness in developing countries. HEV genotype 1 and to some extent genotype 2 are associated with large waterborne outbreaks.
HEV genotypes 1 and 2 are 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. Transfusion-related hepatitis E is increasingly reported from countries in Europe. Rare domestically acquired symptomatic disease is observed in the United States, but its mode of transmission is generally unknown.
Every year HEV causes an estimated 20 million infections with 3.3 million symptomatic cases and 44,000 deaths, and the great majority of these occur in developing countries. 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 recent years, many large international outbreaks have occurred among refugees and internally displaced people living in camps. 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.
During outbreaks of hepatitis E, clinical attack rates are highest in young adults aged 15–49 years. In HEV genotype 1–endemic areas, pregnant women—whether infected sporadically or during an outbreak—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 where infection is caused by HEV genotype 3, 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, mainly from drinking contaminated water. 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.
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, and are indistinguishable from symptoms of other causes of viral hepatitis. Infection with HEV genotype 3, common in developed countries, can progress to chronic infection, whereas genotypes 1, 2, and 4 result only in acute infection. For most people, HEV infection and disease is self-limited. Pregnant women with HEV 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.
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). A safe and effective vaccine has been available in China since 2012; however it is not approved for use elsewhere.