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.
WHO response
In March 2022, Médecins Sans Frontières and South Sudan’s Ministry of Health launched the first hepatitis E vaccination outbreak response campaign at Bentiu internally displaced persons camp in South Sudan’s Unity state. This is the first ever use of the currently only available hepatitis E vaccine, Hecolin, which has been recommended by WHO for outbreak response since 2015. The is a significant milestone for hepatitis E vaccination as one of the key tools, in addition to other control measures, to curb future hepatitis E outbreaks.
WHO has issued the technical report Waterborne outbreaks of hepatitis E: recognition, investigation and control. The manual gives information about the epidemiology, clinical manifestations and diagnosis of hepatitis E. It also provides guidance for public health authorities on how to respond to outbreaks of hepatitis E infection.
WHO is currently working with experts and global partners to develop a generic protocol for use of the hepatitis E vaccine as an outbreak response intervention. There is also ongoing work with similar groups to create a simplified algorithm for the diagnosis, triage and management of hepatitis E during an outbreak.
Global health sector strategies on, respectively, HIV, viral hepatitis, and sexually transmitted infections for the period 2022–2030 (GHSSs) guide the health sector in implementing strategically focused responses to achieve the goals of ending AIDS, viral hepatitis (especially chronic hepatitis B and C) and sexually transmitted infections by 2030.
The GHSS recommend shared and disease-specific country actions supported by actions by WHO and partners. They consider the epidemiological, technological, and contextual shifts of previous years, foster learnings across the disease areas, and create opportunities to leverage innovations and new knowledge for effective responses to the diseases. They call to scale up prevention, testing and treatment of viral hepatitis with a focus to reach populations and communities most affected and at risk for each disease, as well as addressing gaps and inequities. They promote synergies under a universal health coverage and primary health care framework and contribute to achieving the goals of the 2030 Agenda for Sustainable Development.
WHO organizes annual World Hepatitis Day campaigns (as 1 of its 9 flagship annual health campaigns) to increase awareness and understanding of viral hepatitis. For World Hepatitis Day 2023, WHO focuses on the theme “One life, one liver” to illustrate the importance of the liver for a healthy life and the need to scale up viral hepatitis prevention, testing and treatment to prevent liver diseases and achieve the 2030 hepatitis elimination target.