- Every year there are an estimated 20 million hepatitis E infections, over 3 million symptomatic cases of hepatitis E, and 56 600 hepatitis E-related deaths.
- Hepatitis E is usually self-limiting but may develop into fulminant hepatitis (acute liver failure).
- The hepatitis E 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.
- China has produced and licensed the first vaccine to prevent hepatitis E virus infection, although it is not yet available globally.
Hepatitis E is a liver disease caused by the hepatitis E virus: a non-enveloped, positive-sense, single-stranded ribonucleic acid (RNA) virus.
The hepatitis E virus is transmitted mainly through contaminated drinking water. It is usually a self-limiting infection and resolves within 4–6 weeks. Occasionally, a fulminant form of hepatitis develops (acute liver failure), which can lead to death.
Outbreaks and sporadic cases of hepatitis E occur around the world. These outbreaks frequently occur in resource-limited countries with limited access to essential water, sanitation, hygiene and health services, and may affect several hundred to several thousand persons. In recent years, 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 (IDP). An estimated 20 million infections and 3.3 million acute cases occur annually worldwide with an estimated 56 600 deaths1,2.
Hepatitis E is found worldwide and different genotypes of the hepatitis E virus determine differences in epidemiology. For example, genotype 1 is usually seen in developing countries and causes community-level outbreaks while genotype 3 is usually seen in the developed countries and does not cause outbreaks.
The highest seroprevalence rates (number of persons in a population who test positive for the disease) are observed in regions where low standards of sanitation increase the risk for transmission of the virus. East and South Asia are most affected with frequent hepatitis outbreaks, most commonly occurring during the rainy season when water sources become contaminated by faecal material.
The hepatitis E virus is transmitted mainly through the faecal-oral route due to faecal contamination of drinking water. Other transmission routes have been identified, which include:
- foodborne transmission from ingestion of products derived from infected animals;
- transfusion of infected blood products;
- vertical transmission from a pregnant woman to her fetus.
Although humans are considered the natural host for the hepatitis E virus, antibodies to the hepatitis E virus or closely related viruses have been detected in primates and several other animal species.
Hepatitis E is a waterborne disease, and contaminated water or food supplies have been implicated in major outbreaks. The ingestion of raw or uncooked shellfish has also been identified as the source of sporadic cases in endemic areas.
The risk factors for hepatitis E are related to poor sanitation in large areas of the world and shedding of the hepatitis E virus in faeces.
The incubation period following exposure to the hepatitis E virus ranges from 3 to 8 weeks, with a mean of 40 days. The period of communicability is unknown.
The hepatitis E virus causes acute sporadic and epidemic viral hepatitis. Symptomatic infection is most common in young adults aged 15–40 years. Although infection is frequent in children, the disease is mostly asymptomatic or causes a very mild illness without jaundice (anicteric) that goes undiagnosed.
Typical signs and symptoms of hepatitis include:
- jaundice (yellow discolouration of the skin and sclera of the eyes, dark urine and pale stools);
- anorexia (loss of appetite);
- an enlarged, tender liver (hepatomegaly);
- abdominal pain and tenderness;
- nausea and vomiting;
These symptoms are largely indistinguishable from those experienced during any acute phase of hepatic illness and typically last for 1 to 2 weeks.
In rare cases, acute hepatitis E can result in fulminant hepatitis (acute liver failure) and death. Fulminant hepatitis occurs more frequently during pregnancy. Pregnant women are at greater risk of obstetrical complications and mortality from hepatitis E, which can induce a mortality rate of 20% among pregnant women in their third trimester.
Cases of chronic hepatitis E infection have been reported in immunosuppressed people. Reactivation of hepatitis E infection has also been reported in immunocompromised people.
Cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis. Diagnosis of hepatitis E infection is, therefore, usually based on the detection of specific IgM and IgG antibodies to the virus in the blood. Additional tests include reverse transcriptase polymerase chain reaction (RT-PCR) to detect the hepatitis E virus RNA in blood and/or stool, but this assay may require specialised laboratory facilities.
Hepatitis E should be suspected in outbreaks of waterborne hepatitis occurring in developing countries, especially if the disease is more severe in pregnant women, or if hepatitis A has been excluded.
There is no available treatment capable of altering the course of acute hepatitis. Prevention is the most effective approach against the disease.
As hepatitis E is usually self-limiting, hospitalization is generally not required. However, hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.
The risk of infection and transmission can be reduced by:
- maintaining quality standards for public water supplies;
- establishing proper disposal systems to eliminate sanitary waste.
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 drinking water and/or ice of unknown purity;
- adhering to WHO safe food practices.
In 2011, the first vaccine to prevent hepatitis E infection was registered in China. Although it is not available globally, it could potentially become available in a number of other countries.
Guidelines for epidemic measures
In epidemics, WHO recommends:
- determining the mode of transmission;
- identifying the population specifically exposed to increased risk of infection;
- eliminating a common source of infection; and
- improving sanitary and hygienic practices to eliminate faecal contamination of food and water.
WHO has issued a technical report “Waterborne Outbreaks of Hepatitis E: recognition, investigation and control”. The manual gives information about the epidemiology, clinical manifestations of the disease and diagnosis of hepatitis E. It also provides guidance to help public-health authorities respond to outbreaks of hepatitis E infection.
The WHO Strategic Advisory Group of Experts (SAGE) on Immunization issued a position paper on hepatitis E in 2015 which reviewed existing evidence on the burden of hepatitis E and on the safety, immunogenicity, efficacy, and cost-effectiveness of the licensed hepatitis E vaccine. Regarding the use of the hepatitis E vaccine:
- WHO recognizes the importance of hepatitis E as a public health problem in many developing countries, particularly among special populations such as pregnant women and individuals living in camps for displaced persons and in outbreak situations.
- WHO does not make a recommendation on the introduction of the vaccine for routine use in national programmes in populations where epidemic and sporadic hepatitis E disease is common. However, national authorities may decide to use the vaccine based on the local epidemiology.
- 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 <16 years, pregnant women, chronic liver disease patients, and patients on organ transplant waiting lists, and travellers.
- There may be special situations such as outbreaks where the risk of hepatitis E or of 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, the current WHO position on hepatitis E vaccine will be reviewed and updated as necessary on the basis of new information.
In addition to points above, WHO is working in the following areas to prevent and control viral hepatitis:
- raising awareness, promoting partnerships and mobilizing resources;
- formulating evidence-based policy and data for action;
- preventing transmission; and
- executing screening, care and treatment.
WHO also organizes World Hepatitis Day on 28 July every year to increase awareness and understanding of viral hepatitis.
1 Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The Global Burden of Hepatitis E Virus Genotypes 1 and 2 in 2005. Hepatology, Vol. 55, No. 4, 2012: 988-997
2 Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095-2128.