November 05, 2020

Hepatitis E: Cause, Transmission, Symptoms, Treatment and Prevention

Hepatitis E disease is a similar illness to hepatitis A. Like hepatitis A, hepatitis E is spread through contaminated food and drink, and thereafter causes an acute (short-term) and self-limiting illness, from which people usually recover fully with low death rates; however, it can be more severe in pregnant women and people with a weakened immune system e.g. organ transplant recipients, with substantially higher death rates. A preventive vaccine (HEV 239) is approved for use in China, but is not yet available anywhere else.

What is hepatitis E?

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV). Unlike the hepatitis B, hepatitis C and hepatitis D infections, hepatitis E disease is spread through contaminated food and drink just like hepatitis A. See also the separate articles, Hepatitis A: Risk Factors, Symptoms, Diagnosis, Treatment and Prevention, Hepatitis B: Risk Factors, Symptoms, Diagnosis, Prevention and Treatment, and also Hepatitis C: Causes, Symptoms, Diagnosis, Treatment and Prevention, and also Hepatitis D: Transmission, Symptoms, Diagnosis, Treatment and Prevention, for more details on those viral infections.

The hepatitis E virus (HEV) has at least 4 different genetic types: genotypes 1, 2, 3 and 4. Genotypes 1 and 2 have been found only in humans. Genotypes 3 and 4 circulate in several animals (including pigs, wild boars, and deer) without causing any disease, and occasionally infect humans.

The virus is shed in the stools (faeces) of infected persons and enters the human body through the intestine. It is transmitted mainly through contaminated drinking water. Usually the infection is self-limiting and resolves within 2–6 weeks. Occasionally a serious disease, known as fulminant hepatitis (acute liver failure) develops, and a proportion of people with this disease can die.

Abdominal organs, including the liver
Diagram showing abdominal organs, including the liver

How common is hepatitis E? Where is it commonly found?

Hepatitis E infection is found worldwide. Two different patterns are observed, where hepatitis E is found in:
  • resource-poor areas with frequent water contamination; and
  • areas with safe drinking water supplies.
The disease is common in low- and middle-income countries with limited access to essential water, sanitation, hygiene and health services. In these areas, the disease occurs both as outbreaks and as sporadic cases. The outbreaks usually follow periods of fecal contamination of drinking water supplies and may affect several hundred to several thousand persons. Some of these outbreaks have occurred in areas of conflict and humanitarian emergencies, such as war zones, and in camps for refugees or internally displaced populations, situations where sanitation and safe water supply pose special challenges.

Sporadic cases are also believed to be related to contamination of water, albeit at a smaller scale. The cases in these areas are caused mostly by infection with genotype 1 virus, and much less frequently by genotype 2 virus.

In areas with better sanitation and water supply, hepatitis E disease is infrequent, with only occasional sporadic cases. Most of these cases are caused by genotype 3 virus, and are triggered by infection with virus originating in animals, usually through ingestion of undercooked animal meat (including animal liver, particularly pork), and are not related to contamination of water or other foods.

Serological evidence of prior infection with the virus has been found in most areas, with higher seroprevalence rates (proportion of people who test positive for antibodies to HEV) in Asia and Africa. However, presence of these antibodies does not imply presence of or increased risk of disease. The usefulness of such data for epidemiological purposes may also be limited due to variable and possible sub-optimal performance of available serological assays, and possible disappearance of the antibody with the passage of time among those exposed to the virus.

How is hepatitis E transmitted?

The hepatitis E virus is transmitted mainly through the fecal-oral route due to fecal contamination of drinking water. This route accounts for a very large proportion of clinical cases with this disease. The risk factors for hepatitis E are related to poor sanitation, allowing virus excreted in the faeces of infected people to reach drinking water supplies.

Other routes of transmission have been identified but appear to account for a much smaller number of clinical cases. These routes of transmission include:
  • ingestion of undercooked meat or meat products derived from infected animals (e.g. pork liver);
  • transfusion of infected blood and blood products; and
  • vertical transmission from a pregnant woman to her baby.

What are the symptoms of hepatitis E?

The incubation period following exposure to HEV ranges from 2 to 10 weeks, with an average of 5 to 6 weeks. The infected persons excrete the virus beginning from a few days before to 3-4 weeks after onset of the disease.

In areas with high disease endemicity, symptomatic infection is most common in young adults aged 15–40 years. In these areas, although infection does occur in children, they often have either no symptoms or only a mild illness without jaundice which goes undiagnosed.

Typical signs and symptoms of hepatitis include:
  • an initial phase of mild fever, reduced appetite (anorexia), nausea and vomiting, lasting for a few days; some persons may also have abdominal (tummy) pain, itching (without skin lesions), skin rash, or joint pain.
  • jaundice (yellow colour of the skin and white of the eyes), with dark urine and pale stools; and
  • a slightly enlarged, tender liver (hepatomegaly).
These symptoms are often indistinguishable from those experienced during other liver illnesses and typically last 1–6 weeks.

In rare cases, acute hepatitis E can be severe, and result in fulminant hepatitis (acute liver failure); these patients are at risk of death. Fulminant hepatitis occurs more frequently when hepatitis E occurs during pregnancy. Pregnant women with hepatitis E, particularly those in the second or third trimester, are at increased risk of acute liver failure, fetal loss and mortality (death). Up to 20–25% of pregnant women can die if they get hepatitis E in third trimester.

Cases of chronic hepatitis E infection have been reported in immunosuppressed people, particularly organ transplant recipients on immunosuppressive drugs, with genotype 3 or 4 HEV infection. These remain uncommon.

Diagnosis of hepatitis E

Cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis. However, diagnosis can often be strongly suspected in appropriate epidemiologic settings, for example when several cases occur in localities in known disease-endemic areas, or in settings with risk of water contamination, when the disease is more severe in pregnant women, or if hepatitis A has been excluded.

Definitive diagnosis of hepatitis E infection is usually based on the detection of specific IgM antibodies to the virus in a person’s blood; this is usually adequate in areas where disease is common. Rapid tests are available for field use.

Additional tests include reverse transcriptase polymerase chain reaction (RT-PCR) to detect the hepatitis E virus RNA in blood and/or stool; this assay requires specialized laboratory facilities. This test is particularly needed in areas where hepatitis E is infrequent, and in cases with chronic HEV infection.

Treatment of hepatitis E

There is no specific treatment capable of altering the course of acute hepatitis E. As the disease is usually self-limiting, hospitalization is generally not required. Most important is the avoidance of unnecessary medications. Acetaminophen/Paracetamol and medication against vomiting should not be given.

However, hospitalization is required for people with fulminant hepatitis, and should also be considered for symptomatic pregnant women.

Immunosuppressed people with chronic hepatitis E benefit from specific treatment using ribavirin, an antiviral drug. In some specific situations, interferon has also been used successfully.

Prevention of hepatitis E

Prevention is the most effective approach against the HEV disease. At the population level, transmission of HEV and hepatitis E disease can be reduced by:
  • maintaining quality standards for public water supplies; and
  • establishing proper disposal systems for human faeces.
On an individual level, infection risk can be reduced by:
  • maintaining hygienic practices;
  • avoiding consumption of water and ice of unknown purity.
In 2011, a recombinant subunit vaccine to prevent hepatitis E virus infection was registered in China. It has not yet been approved in other countries.

In 2015, the World Health Organization (WHO) made the following recommendation regarding the use of the HEV vaccine, currently available only in China:
  • Due to the lack of sufficient information on safety, immunogenicity, and efficacy in the following population subgroups, WHO does not recommend routine use of the vaccine in children aged under 16 years, pregnant women, people with chronic liver disease, people on organ transplant waiting lists, and travellers.
  • There may be special situations such as outbreaks where the risk of hepatitis E or its complications or mortality is particularly high. The current WHO position concerning routine programmes should not preclude the use of the vaccine in these specific situations. In particular, the use of the vaccine to mitigate or prevent outbreaks of hepatitis E should be considered as well as the use of the vaccine to mitigate consequences in high risk groups such as pregnant women.
  • As further data become available, WHO's position on hepatitis E vaccine will be reviewed and updated as necessary on the basis of new information.
1). World Health Organization (July 2020). Hepatitis E. Available Online.
2). Centers for Disease Control (June 2020). Hepatitis E. Available Online.
3). David B Rein, Gretchen A Stevens, Jordan Theaker et al: The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2012 Apr;55(4):988-97. doi: 10.1002/hep.25505. Available Online.

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