Hepatitis E is an infectious disease caused by hepatitis E virus, or HEV, and is primarily an acute inflammatory illness of the liver. HEV belongs to the Hepeviridae family and contains a positive-sense RNA genome. Several genotypes infect humans, with genotypes 1 and 2 predominantly associated with human-to-human faecal-oral transmission and genotypes 3 and 4 associated particularly with zoonotic transmission. Unlike hepatitis D, HEV does not require another hepatitis virus for replication.
Infection is frequently self-limiting, with many people recovering without specific antiviral treatment, but the disease can occasionally become severe and cause fulminant hepatitis and acute liver failure. WHO estimates that around 20 million HEV infections occur globally each year, of which about 3.3 million are symptomatic.
Transmission patterns differ according to viral genotype and geographical setting. Genotypes 1 and 2 are primarily transmitted through the faecal-oral route, particularly through drinking water contaminated with human faeces, and can cause large outbreaks where sanitation and clean-water infrastructure are inadequate. Genotypes 3 and 4 are associated more strongly with zoonotic transmission, including consumption of raw or undercooked meat from infected animals. HEV is therefore both a waterborne public-health problem and, in some settings, a foodborne zoonotic infection. Poor sanitation, inadequate water treatment, humanitarian emergencies and displacement can increase outbreak risk. Individual prevention includes safe drinking water, good hand hygiene and appropriate food preparation. Public-health prevention depends heavily on water, sanitation and hygiene infrastructure.
The incubation period for hepatitis E is generally several weeks, with WHO describing a range of approximately two to ten weeks and an average around five to six weeks. Many infections are asymptomatic, particularly in children in areas where HEV is common. When illness occurs, an initial phase may include fever, reduced appetite, nausea, vomiting, abdominal discomfort and general malaise, followed by jaundice, dark urine and pale stools. Itching, rash, joint pain and liver enlargement can also occur. Because these manifestations overlap with other forms of acute viral hepatitis and other illnesses producing jaundice, symptoms alone cannot reliably establish the diagnosis. Most symptomatic episodes resolve over weeks, but severity varies substantially between individuals and clinical contexts.
Diagnosis generally combines clinical and epidemiological assessment with laboratory testing. Detection of anti-HEV immunoglobulin M in blood is commonly used to support diagnosis of recent infection, while reverse-transcription polymerase chain reaction can detect HEV RNA in blood or stool and is particularly useful in unusual, severe or chronic cases. Liver tests commonly show raised alanine aminotransferase and aspartate aminotransferase concentrations, with bilirubin often increasing when jaundice occurs. Diagnosis can be challenging in countries where HEV is less frequently considered, because its symptoms resemble hepatitis A and other causes of acute hepatitis. Molecular testing is especially valuable when infection is suspected in immunosuppressed patients or when persistent infection is being investigated.
Most acute hepatitis E infections require supportive rather than disease-specific treatment because the infection commonly resolves spontaneously. Adequate hydration, nutritional support and clinical monitoring are important, while potentially hepatotoxic medicines should be reviewed by a healthcare professional. Severe disease with acute liver failure requires hospital management, and symptomatic pregnant patients may require particularly careful assessment because pregnancy, especially later pregnancy, is associated with substantially increased risk of severe disease and adverse fetal outcomes in some outbreaks. Chronic HEV infection is uncommon but has been documented particularly in immunosuppressed people, including some solid-organ transplant recipients. In such cases, reduction of immunosuppression may sometimes form part of specialist management, and antiviral treatment such as ribavirin may be considered under specialist supervision.
Pregnancy is a particularly important clinical context in hepatitis E because the consequences can be markedly more severe than in many other populations. WHO reports increased risk of fulminant hepatitis, fetal loss and maternal death among infected pregnant women, particularly during the second and third trimesters. The reasons for this severe clinical pattern involve complex interactions between viral biology, pregnancy-associated immune changes and host physiology.
Hepatitis E should therefore be considered when a pregnant person develops an acute hepatitis syndrome or jaundice in an appropriate epidemiological setting. The diagnosis should not be dismissed simply because hepatitis A or another common cause is more familiar. Rapid assessment is important when there are signs of liver failure, altered mental state, bleeding tendency or other evidence of severe hepatic dysfunction.
Prevention differs fundamentally from hepatitis B and hepatitis D because there is no globally deployed universal HEV vaccination programme comparable with routine hepatitis B immunisation. An HEV vaccine has been licensed in China and has also been used in certain outbreak-response settings, but availability is geographically limited. Consequently, sanitation, safe water, hand hygiene and food safety remain central prevention measures.
The distinction between HEV and other hepatitis viruses is also important: HEV is not transmitted principally through the same blood-borne mechanisms as hepatitis B, C and D in typical endemic outbreaks. Conversely, zoonotic HEV means that food preparation can be relevant in countries with excellent sanitation. The disease therefore demonstrates how the same named infection can have different epidemiological patterns according to viral genotype, geography, host factors and exposure route.
Hepatitis E is significant because it connects infectious disease, environmental health, food safety, pregnancy and liver medicine. It can occur as isolated cases or large outbreaks, particularly where contaminated water reaches large populations. It is frequently self-limiting but cannot be assumed to be harmless, because severe acute liver failure can occur and chronic infection is possible in selected immunosuppressed patients.
Its relationship with liver failure also distinguishes uncomplicated hepatitis E from fulminant disease, in which hepatic synthetic and metabolic functions deteriorate rapidly. A useful conceptual distinction is therefore between infection, acute hepatitis, severe hepatitis and acute liver failure rather than treating them as interchangeable terms. Accurate recognition depends on laboratory confirmation and attention to epidemiological context, especially travel, water exposure, food exposure, pregnancy and immune status.
