Hepatitis E

Hepatitis E is inflammation of the liver caused by infection with the hepatitis E virus (HEV); it is a type of viral hepatitis. Hepatitis E has mainly a fecal-oral transmission route that is similar to hepatitis A, although the viruses are unrelated. HEV is a positive-sense, single-stranded, nonenveloped, RNA icosahedral virus and one of five known human hepatitis viruses: A, B, C, D, and E.

Like hepatitis A, hepatitis E usually follows an acute and self-limiting course of illness (the condition is temporary and the individual recovers) with low death rates in resource-rich areas; however, it can be more severe in pregnant women and people with a weakened immune system, with substantially higher death rates. In pregnant women, especially in the third trimester, the disease is more often severe and is associated with a clinical syndrome called fulminant liver failure, with death rates around 20%. Whereas pregnant women may have a rapid and severe course, organ transplant recipients who receive medications to weaken the immune system and prevent organ rejection can develop a slower and more persistent form called chronic hepatitis E, which is so diagnosed after 3 months of continuous viremia. HEV can be clustered genetically into 8 genotypes, and genotypes 3 and 4 tend to be the ones that cause chronic hepatitis in the immunosuppressed.

In 2017, hepatitis E was estimated to affect more than 19 million people. Those most commonly at risk of HEV are men aged 15 to 35 years of age. A preventive vaccine (HEV 239) is approved for use in China.

The virus was discovered in 1983 by researchers investigating an outbreak of unexplained hepatitis among Soviet soldiers serving in Afghanistan. The earliest well-documented epidemic of hepatitis E occurred in 1955 in New Delhi and affected tens of thousands of people (hepatitis E virus was identified as the etiological agent at fault retrospectively through testing of stored samples).

The average incubation period of hepatitis E is 40 days, ranging from 2 to 8 weeks. After a short prodromal phase symptoms may include jaundice, fatigue, and nausea, though most HEV infections are asymptomatic. The symptomatic phase coincides with elevated hepatic aminotransferase levels. Viral RNA becomes detectable in stool and blood serum during the incubation period. Serum IgM and IgG antibodies against HEV appear just before the onset of clinical symptoms. Recovery leads to virus clearance from the blood, while the virus may persist in stool for much longer. Recovery is also marked by disappearance of IgM antibodies and increase of levels of IgG antibodies.

While usually lasting weeks and then resolving, in people with weakened immune systems—particularly in people who have had solid organ transplant—hepatitis E may cause a chronic infection. Occasionally this may result in a life-threatening illness such as fulminant liver failure or liver cirrhosis.

Infection with hepatitis E virus can also lead to problems in other organs. For some of these reported conditions such as musculoskeletal or immune-mediated manifestations the relationship is not entirely clear, but for several neurological and blood conditions the relationship appears more consistent:

Pregnant women show a more severe course of infection than other populations. Liver failure with mortality rates of 20% to 25% has been reported from outbreaks of genotype 1 and 2 HEV in developing countries. Besides signs of an acute infections, adverse effects on the mother and fetus may include preterm delivery, abortion, stillbirth, and neonatal death.