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Hepatitis E

20 July 2023

Key facts

  • Hepatitis E is an inflammation of the liver caused by infection with the hepatitis E virus (HEV).

  • Every year there are an estimated 20 million HEV infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E.

  • WHO estimates that hepatitis E caused approximately 44 000 deaths in 2015 (accounting for 3.3% of the mortality due to viral hepatitis).

  • The virus is transmitted via the fecal-oral route, principally via contaminated water.

  • Hepatitis E is found worldwide, but the disease is most common in East and South Asia.

  • A vaccine to prevent hepatitis E virus infection has been developed and is licensed in China, but is not yet available elsewhere.

Overview

Hepatitis E is inflammation of the liver caused by the hepatitis E virus (HEV). The virus has at least 4 different 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 of infected persons and enters the human body through the intestine. It is transmitted mainly through contaminated drinking water. The infection is usually self-limiting and resolves within 2–6 weeks. Occasionally a serious disease known as fulminant hepatitis (acute liver failure) develops, which can be fatal.

Transmission

 

Hepatitis E infection is found worldwide and 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 faecal 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 camps for refugees or internally displaced populations, 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 infection 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). These cases are not related to contamination of water or other foods.

Symptoms

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, it often goes undiagnosed because they typically have no symptoms or only a mild illness without jaundice.

Typical signs and symptoms of hepatitis include:

  • an initial phase of mild fever, reduced appetite (anorexia), nausea and vomiting lasting for a few days;

  • abdominal pain, itching , skin rash, or joint pain;

  • jaundice (yellow colour of the skin), 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. 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. 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

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, 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 anti-HEV immunoglobulin M (IgM) antibodies to the virus in a person’s blood; this is usually adequate in areas where the 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 stool. This assay requires specialized laboratory facilities. This test is particularly needed in areas where hepatitis E is infrequent and in uncommon cases with chronic HEV infection.

Treatment

 

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. It is important to avoid unnecessary medications that can adversely affect liver function, e.g. acetaminophen, paracetamol.

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

 

Prevention is the most effective approach against the infection. At the population level, transmission of HEV and hepatitis E infection 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; and

  • avoiding consumption of water and ice of unknown purity.

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