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. In retrospect, the earliest known epidemic of hepatitis E occurred in 1955 in New Delhi, but the virus was not isolated until 1983 by Russian scientists investigating an outbreak in Afghanistan. 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.
Signs and symptoms
Acute infection
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.
Chronic infection
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.
Other organs
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: Acute pancreatitis (HEV genotype 1) Neurological complications (though the mechanism of neurological damage is unknown at this point.) include: Guillain-Barré syndrome (acute limb weakness due to nerve involvement), neuralgic amyotrophy (arm and shoulder weakness, also known as Parsonage-Turner syndrome), acute transverse myelitis and acute meningoencephalitis. Glomerulonephritis with nephrotic syndrome and/or cryoglobulinemia Mixed cryoglobulinemia, where antibodies in the bloodstream react inappropriately at low temperatures Severe thrombocytopenia (low platelet count in the blood) which confers an increased risk of dangerous bleeding
Infection in pregnancy
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.
The pathological and biological mechanisms behind the adverse outcomes of pregnancy infections remain largely unclear. Increased viral replication and influence of hormonal changes on the immune system are currently thought to contribute to worsening the course of infection. Furthermore, studies showing evidence for viral replication in the placenta or reporting the full viral life cycle in placental-derived cells in vitro suggest that the human placenta may be a site of viral replication outside the liver. The primary reason for HEV severity in pregnancy remains enigmatic.