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

Most infections cause no symptoms or a self-limiting acute illness, with recovery occurring over several weeks. However, HEV can sometimes cause severe hepatitis and acute liver failure.

In people who are immunosuppressed, particularly solid-organ transplant recipients, infection can become chronic. HEV is also associated with disease beyond the liver, including neurological manifestations.

The global burden is substantial. WHO estimates that approximately 20 million HEV infections occur each year, resulting in around 3.3 million symptomatic infections.

HEV is genetically diverse. Several genotypes exist, but genotypes 1–4 account for the great majority of recognised human disease worldwide.

The distinction matters because different genotypes have very different epidemiology.

HEV-1 and HEV-2 primarily infect humans, whereas HEV-3 and HEV-4 mainly infect non-human mammals and can cross into humans.

Less common HEV genotypes and related viruses also have emerging relevance to human infection.

There isn't one universal route of HEV transmission.

WATERBORNE TRANSMISSION

For HEV-1 and HEV-2, infection is principally spread by the faecal–oral route, particularly through drinking water contaminated with human faeces.

This can lead to large outbreaks where access to clean water and sanitation is limited, including humanitarian and displacement settings.

ZOONOTIC & FOODBORNE TRANSMISSION

HEV-3 and HEV-4 infect a number of mammalian species. Humans can acquire infection through zoonotic transmission, particularly through consumption of raw or inadequately cooked infected meat or animal products.

Pigs and wild boar are particularly important reservoirs. Pork, pig liver products, wild boar and venison have all been associated with human infection.

THE ENVIRONMENT

HEV can also be detected in environmental sources, including wastewater. The contribution of different environmental pathways to human infection remains an active area of research.

HEV infection occurs worldwide, but its epidemiology differs markedly between regions.

HEV-1 and HEV-2 cause sporadic disease and outbreaks particularly in regions where access to safe water and sanitation may be limited. Sub-Saharan Africa and East and South Asia carry a particularly high burden.

HEV-3 is widely distributed and causes locally acquired infections in many higher-income countries, where zoonotic and foodborne transmission are particularly important.

HEV-4 is also zoonotic and is especially associated with parts of Asia.

The people most likely to become infected and those most likely to develop serious disease are not necessarily the same.

Many HEV infections cause no symptoms at all.

When acute hepatitis E is symptomatic, illness may include:

Fatigue • loss of appetite • nausea • vomiting • abdominal discomfort • fever • dark urine • pale stools • itching • jaundice

Symptoms typically develop several weeks after exposure. The incubation period is approximately 2–10 weeks, averaging around 5–6 weeks.

Most people recover completely.

SEVERE ACUTE HEPATITIS

A minority of infections can cause severe hepatitis and acute liver failure.

CHRONIC HEV

In immunosuppressed people, particularly transplant recipients, HEV infection can persist and become chronic. Chronic infection can lead to progressive liver disease.

BEYOND THE LIVER

Clinical features alone cannot reliably distinguish hepatitis E from other causes of acute hepatitis. Laboratory testing is therefore essential.

For most immunocompetent people with uncomplicated acute hepatitis E, infection is self-limiting and specific antiviral treatment is not required.

Severe acute hepatitis, acute liver failure, pregnancy with symptomatic disease and infection in people with underlying liver disease require appropriate clinical assessment and, where indicated, specialist care.

Management of chronic HEV is different.

In solid-organ transplant recipients, reduction of immunosuppression may allow viral clearance in some patients when clinically possible.

For persistent infection, ribavirin is used in specialist management of chronic HEV.

Because HEV transmission differs around the world, prevention also depends on setting.