Hepatitis E virus (HEV) is an enterically transmitted infection that is typically self-limited. It is spread by fecally contaminated water within endemic areas. Outbreaks can be epidemic and individual. Hepatitis E has many similarities with hepatitis A. Hepatitis E infection has recently been associated with chronic hepatitis in solid organ-transplant recipients.1
HEV was discovered during electron microscopy of feces contaminated with enteric non-A, non-B hepatitis. The virus is icosahedral and nonenveloped. It has a diameter of approximately 34 nanometers, and it contains a single strand of RNA approximately 7.5 kilobases in length.
Hepatitis E is an RNA virus of the genus Hepevirus. Four hepatitis E genotypes exist, and genotype 1 causes human disease.
The most exciting recent advancement has been the development of a successful recombinant hepatitis E vaccine.2
The HEV genome contains 3 open reading frames (ORFs). The largest, ORF-1, codes for the nonstructural proteins responsible for viral replication. ORF-2 contains genes encoding the capsid. The function of ORF-3 is unknown, but the antibodies directed against ORF-3 epitopes have been identified.
The prevalence rate of anti-HEV antibodies is less than 2%. The route of exposure is unknown but generally is attributed to travel in endemic areas.
Hepatitis E has worldwide distribution, but predominating factors include tropical climates, inadequate sanitation, and poor personal hygiene. It is found most often in developing countries near the equator, in both the Eastern and Western hemispheres. Outbreaks are associated with rainy seasons, floods, and overcrowding. Water supply contamination with human feces is a frequent source of epidemics. The largest outbreak was reported in northeast China, with 100,000 people affected between 1986 and 1988. The reservoir of HEV is unknown, but it may be transmitted by animals.
The overall case fatality rate is 4%.
The case fatality rate among pregnant women is 20%, which increases during the second and third trimesters. Reported causes of death include encephalopathy and disseminated intravascular coagulation.
The rate of fulminant hepatic failure in infected pregnant women is high.
Infection has no apparent racial predilection.
Although predilection is unknown, pregnant women are prone to complications.
Hepatitis E predominantly affects those aged 15-40 years.
It may affect younger age groups but generally is not recognized and may be subclinical.
No chronic cases have been described.
The incubation period ranges from 15 days to 60 days, and the course of infection has 2 phases termed prodromal and icteric.
Prodromal-phase symptoms include the following:
Fever with mild temperature elevations (25-97%)
Weight loss (typically 2-4 kg)
Right upper quadrant pain that increases with physical activity
Icteric-phase symptoms include the following:
Jaundice – May be difficult to see with some patients’ natural skin color; serum bilirubin level is greater than 3 mg/dL; scleral icterus is present
Light-colored stools (20-40%)
Other features include the following:
Rapidly increasing serum amino transferase (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) levels that peak within 4-6 weeks of onset and gradually decrease to normal within 1-2 months
Viral excretion in stool persisting 14 days from onset
Symptoms of HEV are similar to other hepatitides and include the following:
Abdominal pain (35-80% of patients)
When or how long the patient is infectious cannot be determined, but infectivity may relate to the presence of the virus in the stool.
Right upper quadrant tenderness
Possible enlarged liver (palpable edges)
Possible transient spider angiomata
HEV is spread by fecally contaminated water within endemic areas. See Background.