Hepatitis E virus is an unclassified virus (initially thought to be a calicivirus) that is the major cause of "non-A, non-B enterically-acquired hepatitis" in humans.

HEV has been responsible for large-scale outbreaks of hepatitis among young adults in many parts of the world (Asia, Africa, Mexico), but no outbreaks have been reported in the U.S.- only sporadic individual cases. Nonetheless, antibodies may be found in apparently healthy individuals in non-endemic countries. The rate of seropositivity in non-endemic countries was initially found to be ~1-2%, but in a recent study, 17-18% of blood donor samples tested from 8 states in the U.S. were positive for anti-HEV antibodies. In the same study, 23-26% of swine veterinarians were seropositive.

• Interestingly, the mortality rate following HEV infection is much higher among pregnant woman (approaching 20%) than in the general population.
  • The infection is most severe when contracted during the third trimester.
  • The reason for this pattern of enhanced disease is not known.

Might pigs or other animals play a role in the epidemiology of HEV infection in humans?

The reservoir of HEV has been assumed to humans themselves. However, several recent findings suggest that pigs may play a role:

• A HEV-like virus (swine HEV [swHEV]) was isolated from pigs in the U.S. in 1997. Serologic testing indicates that this virus is widespread in pigs:
  • >80% seropositivity by 4-5 months of age among pigs in the U.S.
  • 38-56% seropositivity among Canadian pigs
  • 37% seropositivity among pigs in Taiwan
  • 30% seropositivity among pigs in Australia
• Though clinically normal, infected pigs have histologic evidence of hepatitis, including multifocal lymphoplasmacytic hepatitis and focal hepatocellular necrosis. In addition, the virus may also replicate in lymph nodes and the colon.
• Sequence analysis of swHEV indicates that it is highly homologous to, but distinct from, most strains of human HEV. However, swHEV-like viruses (US1 and US2 strains with 94-98% sequence homology to swHEV itself) have been isolated from people in the U.S. The swHEV has been shown to infect non-human primates and the human US1 and US2 strains have also been shown to infect pigs.
  • Similar pairs of closely related human and swine isolates have also been reported in Taiwan, Japan, China, Korea, and The Netherlands. Enhanced rates of seropositivity among persons associated with swine as described above.
    • In Japan in 2003, people were infected with HEV after consuming raw pork liver. Follow-up studies detected HEV genetic sequences in the liver product. Human infections were also associated with consumption of raw wild boar liver and raw deer meat.
• Anti-HEV antibodies have also been detected in rodents, chickens, dogs, cows, sheep and goats, and HEV-like viruses have been isolated from chickens, rodents, and deer.

Many questions remain regarding the relationship between swHEV and huHEV.

• Could exposure to swHEV in people explain the occurrence of seropositivity to human HEV in non-endemic regions of the world, including the U.S.?
  • Or exposure to other animals...anti-HEV antibodies have also been detected in rodents, chickens, dogs, cows, sheep and goats.
• Might swHEV be a possible candidate vaccine strain for humans?

References:

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