What is Hepatitis E

Hepatitis E is a liver infection caused by the Hepatitis E virus (HEV): a small virus, with a positive-sense, single-stranded ribonucleic acid (RNA) genome ¹⁾. The virus has at least 4 different types: genotypes 1, 2, 3 and 4. Genotypes 1 and 2 have been found only in humans. Genotype 3 and 4 viruses circulate in several animals (including pigs, wild boars, and deer) without causing any disease, and occasionally infect humans. Hepatitis E is a self-limited disease that does not result in chronic infection. While rare in the United States, Hepatitis E is common in many parts of the world. It is transmitted from ingestion of fecal matter, even in microscopic amounts, and is usually associated with contaminated water supply in countries with poor sanitation. There is currently no FDA-approved vaccine for Hepatitis E ²⁾.

Hepatitis E Key facts ²⁾:

• Hepatitis E is a liver disease caused by infection with a virus known as hepatitis E virus (HEV).
• Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E ³⁾.
• The World Health Organization (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 faecal-oral route, principally via contaminated water.
• Hepatitis E is found worldwide, but the prevalence is highest in East and South Asia.
• A vaccine to prevent hepatitis E virus infection has been developed (2011) and is licensed in China, but is not yet available elsewhere.

Hepatitis E typically causes acute, or short-term, infection.

Hepatitis E Vaccine

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 ⁴⁾. No FDA-approved vaccine for Hepatitis E is currently available in the United States.

What is Acute hepatitis E

Acute hepatitis E is a short-term infection. In most cases, people’s bodies are able to recover and fight off the infection and the virus goes away. People usually get better without treatment after several weeks.

Can Hepatitis E become chronic ?

To date, there is no report of progression of acute hepatitis E to chronic Hepatitis E in developing countries where hepatitis E virus (HEV) genotypes 1 and 2 are the predominant causes of illness. However, more and more cases of Hepatitis E with progression to chronic hepatitis and chronic liver disease are being reported among hepatitis E virus (HEV) genotype 3 cases acquired in the developed countries. These chronic cases are exclusively among persons who are on immunosuppressive treatment for solid organ transplant.

What is Chronic hepatitis E

Chronic hepatitis E is a long-lasting infection that occurs when your body isn’t able to fight off the virus and the virus does not go away. Chronic hepatitis E is rare and only occurs in people with weakened immune systems. For example, hepatitis E may become chronic in people taking medicines that weaken their immune system after an organ transplant, or in people who have HIV or AIDS.

How serious is hepatitis E ?

Most people with Hepatitis E recover completely. During hepatitis E virus outbreaks, the overall case-fatality rate is about 1%.

The types of hepatitis E that are common in developing countries are likely to cause severe infections, especially in pregnant women.

For pregnant women, Hepatitis E can be a serious illness with mortality reaching 10%–30% in their third trimester of pregnancy. Hepatitis E could also be serious among persons with preexisting chronic liver disease resulting in decompensated liver disease and death. Similarly high mortality occurs solid organ transplant recipients on immunosuppressive therapy.

The types of hepatitis E that are common in developed countries are often mild and cause no symptoms. Many people don’t know they’ve had these types of hepatitis E.

How common is Hepatitis E in the United States ?

Hepatitis E is believed to be uncommon in the United States ⁵⁾. However, some studies have found a high prevalence of antibodies to hepatitis E virus (HEV) in the general population. When symptomatic hepatitis E does occur, it is usually the result of travel to a developing country where hepatitis E is endemic. Increasingly, sporadic Hepatitis E cases not associated with travel have been identified in developed countries. No clear exposure was identified for these domestically acquired (non-travel related) cases.

Where is Hepatitis E most common ?

Hepatitis E is more common in developing countries, where sanitation is poor and access to clean water is limited.

Although experts used to think hepatitis E was rare in the United States, recent research suggests that about 20 percent of the population has had hepatitis E ⁶⁾.

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 resource-limited 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.

Figure 1. Hepatitis E worldwide locations

Sporadic cases are also believed to be related to contamination of water or food, 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 caused by infection with virus originating in animals, usually through ingestion of undercooked animal meat (including animal liver) and are not related to contamination of water or other foods.

Serological evidence of prior exposure to the virus has been found in most areas, with higher seroprevalence rates [proportion of people who test positive for IgG antibodies to hepatitis E virus (HEV)] in regions with lower standards of sanitation and thus higher risk for transmission. 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 do you get Hepatitis E ?

The hepatitis E virus is transmitted mainly through the fecal-oral route due to fecal contamination of drinking water. 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. This route accounts for a very large proportion of clinical cases with this disease. 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.

• Some types are spread by drinking contaminated water. These types are more common in developing countries, including parts of Africa, Asia, Central America, and the Middle East ⁷⁾.
• Other types are spread by eating under cooked pork or wild game, such as deer. These types are more common in developed countries, such as the United States, Australia, Japan, and parts of Europe and East Asia ⁸⁾. The ingestion of raw or uncooked shellfish may be the source of sporadic cases in endemic areas.
• Other routes of transmission have been identified, but appear to account for a much smaller number of clinical cases:
  • transfusion of infected blood products; and
  • vertical transmission from a pregnant woman to her fetus.

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.

Who is more likely to get hepatitis E ?

Different types of hepatitis E are more likely to affect different groups of people. The types of hepatitis E that are more common in developing countries are more likely to affect adolescents and young adults ⁹⁾.

In contrast, the types of hepatitis E that are more common in developed countries most often affect older men ¹⁰⁾.

How can I protect myself from hepatitis E infection ?

When traveling in a developing country, drink bottled water. Use bottled water to brush your teeth, make ice cubes, and wash fruits and vegetables.

Also, make sure any pork or deer you eat is thoroughly cooked, both in developing countries and in developed countries such as the United States.

How can I prevent spreading hepatitis E to others ?

Research suggests that it is uncommon for people to spread hepatitis E directly to other people. If you have hepatitis E, you can reduce your chance of spreading the infection by washing your hands with warm, soapy water after using the toilet and before preparing food. Talk with a blood donation center before you donate blood.

Is a hepatitis E vaccine available ?

No vaccine for hepatitis E is available in the United States. Vaccines have been developed and are used in China.

Prevention of Hepatitis E

Prevention is the most effective approach against the disease. At the population level, transmission of HEV and hepatitis E disease can be reduced by:

• maintaining quality standards for public water supplies;
• establishing proper disposal systems for human feces.

On an individual level, infection risk can be reduced by:

• maintaining hygienic practices such as hand-washing with safe water, particularly before handling food;
• avoiding consumption of water and/or ice of unknown purity; and
• adhering to World Health Organization (WHO) safe food practices.

Immune globulin is not effective in preventing Hepatitis E.

Hepatitis E Symptoms

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

Many people infected with hepatitis E have no symptoms. Some people have symptoms 15 to 60 days (mean: 40 days) after they become infected with the virus ¹¹⁾.

The ratio of symptomatic to asymptomatic infection ranges from 1:2 to 1:13.

Typical signs and symptoms of hepatitis include:

• feeling tired
• nausea and vomiting
• poor appetite (anorexia)
• pain over the liver, in the upper part of the abdomen
• a slightly enlarged, tender liver (hepatomegaly).
• itching (without skin lesions), skin rash, or joint pain.
• darkening of the color of urine
• pale stools
• yellowish tint to the whites of the eyes and skin, called jaundice

People with hepatitis E typically get better without treatment after several weeks.

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 that goes undiagnosed.

These symptoms are often indistinguishable from those experienced during other liver illnesses and typically last between 1–6 weeks.

In rare cases, acute hepatitis E can be severe, and results 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 an increased risk of acute liver failure, fetal loss and mortality. Case fatality rates as high as 20–25% have been reported among pregnant women in their 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 hepatitis E virus infection.

Who is most likely to have symptomatic hepatitis E virus infection ?

Symptomatic Hepatitis E in developing countries commonly occurs among older adolescents and young adults (aged 15–44 years). Pregnant women are more likely to experience severe illness including fulminant hepatitis and death.

In developed countries, sporadic cases due to hepatitis E virus genotype 3 mainly affect older men (>40 years of age). Acute and chronic hepatitis E virus infection occur in solid organ transplant recipients on immunosuppressant therapy.

How long does an hepatitis E virus (HEV)-infected person remain infectious ?

The period of infectiousness has not been clearly determined, but virus excretion in stool has been demonstrated from one week prior to onset up to 30 days after the onset of jaundice. Chronically infected persons shed virus as long as infected.

How do doctors diagnose hepatitis E ?

Cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis. Doctors diagnose hepatitis E based on symptoms and blood tests. A health care professional will take a blood sample from you and send the sample to a lab. Blood tests can detect antibodies to the hepatitis E virus and show whether you have hepatitis E. The virus can also be detected in blood and in stool samples taken during acute hepatitis E infection.

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.

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 specialised laboratory facilities. This test is particularly needed in areas where hepatitis E is infrequent, and in cases with chronic hepatitis E virus (HEV) infection.

A test for viral antigen detection in serum has been developed; its place in the diagnosis of hepatitis E is currently being studied.

Treatment Hepatitis E virus (HEV) Infection

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. Treatment for acute hepatitis E includes resting, drinking plenty of liquids, and eating healthy foods to help relieve symptoms.

Hospitalization is only required for people with fulminant hepatitis, however, and should also be considered for symptomatic pregnant women.

Talk with your doctor before taking any prescription or over-the-counter medicines, vitamins or other dietary supplements , or complementary or alternative medicines—any of these could damage your liver. You should avoid alcohol until your doctor tells you that you have completely recovered from hepatitis E.

See your doctor regularly to make sure your body has fully recovered.

Doctors may treat chronic hepatitis E with ribavirin or peginterferon alfa-2a (Pegasys).

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

What should I eat and drink if I have hepatitis E ?

If you have hepatitis E, you should eat a balanced, healthy diet. Talk with your doctor about healthy eating. You should also avoid alcohol because it can cause more liver damage.