Page Banner

United States Department of Agriculture

Agricultural Research Service

headline bar

The Organism, Its Disease and Habitat:

Hepatitis E virus (HEV) induces a human viral hepatitis disease seen principally in developing countries. The source of hepatitis E virus is considered to be water or food contaminated by human feces (Aggarwal and Naik 1997). Recently, Meng et al (1997) isolated a HEV strain from the feces and sera of pigs from herds in the midwestern United States which was closely related, but not identical, to human HEV strains. Seropositivity to HEV was demonstrated in 79% (192/243) of pigs 2 months old (Meng et al 1997). The implication of the findings obtained by Meng and coworkers suggest that HEV is a zoonotic virus with far-reaching ramifications in terms of hepatitis E epidemiology and infection. 

Hepatitis E virus is a spherical, non-enveloped, single stranded, positive-sense RNA virus. There are three well-characterized genotypes of human HEV: Asia-Africa, Mexico, and United States. These genotypes can not be differentiated by serology, but the viral RNA nucleotide sequence is different for each genotype. The genotypes are geographically isolated (Schlauder et al 1999; Tsarev et al 1999). Hepatitis E viruses are a major cause of outbreak and sporadic cases of human viral hepatitis in tropical and sub-tropical countries (Yarbough 1999). In industrialized countries, outbreaks of hepatitis E have not been observed, but the disease has been diagnosed occasionally in travelers returning from trips to HEV-endemic areas (Favorov and Margolis 1999; Langer and Frösner 1996). A few sporadic cases not related to travel or contact with HEV-infected individuals have also been reported in developed countries (McCrudden et al 2000; Tsang et al 2000).

The disease. 

Hepatitis E in most patients is a moderately severe icteric (jaundice) disease with a self-limited course similar to that seen in hepatitis A infections. Jaundice is usually accompanied by malaise, anorexia, abdominal pain, liver enlargement, vomiting, and fever (Chauhan et al 1993; Mast and Krawczynski 1996; Ticehurst 1995). A hepatitis E infection does not lead to long-term shedding of the virus, liver chronicity or cirrhosis of the liver. The case-fatality rate for hepatitis E infection ranges from 0.5-3%, except in pregnant women where it ranges from 15-25% (Mast and Krawczynski 1996; Ticehurst 1995). No treatment is available.

Transmission and target populations

Hepatitis E virus is transmitted principally by the fecal-oral route. Massive outbreaks of hepatitis E involving thousands of cases occur periodically in HEV endemic countries and are generally due to the drinking of fecally-contaminated water (Aggarwal and Naik 1997; Labrique et al 1999; Mast and Krawcznski 1996). There is a definite potential for food borne transmission, but corroborating information is lacking. Person-to-person transmission has been documented (Khuroo and Dar 1992; Robson et al 1992), but is considered to be a minor means of transmission (Aggarwal and Naik 1997).

Unlike hepatitis A in which young children are most commonly infected, hepatitis E is seen most often in the 15-40 year old population (Aggarwal and Naik 1997). Pregnant women, however, are more likely to be infected by HEV, more likely to develop fulminant hepatic failure and more likely to die with concomitant loss of the fetus (Khuroo et al 1981; Tsega et al 1993).

Swine HEV

Meng et al (1997) designated a virus isolated from pigs in the midwestern United States that cross-reacted with antibody to the capsid antigen of human HEV, as swine HEV. The United States swine HEV had the greatest degree of similarity to the United States genotype of human HEV, with a homology of 92% at the nucleotide level (Erker et al 1999; Schlauder et al 1998). US swine hepatitis E was less closely related to the Asia-Africa and Mexico genotypes of human HEV strains, with 79-80% nucleotide sequence identity (Meng et al 1997).

Pigs naturally infected with the United States swine HEV are asymptomatic and appear clinically normal, but they do show anti-HEV antibodies, viremia and virus excretion (Meng et al 1997). Specific pathogen-free (SPF) pigs infected with swine HEV were anti-HEV positive and virus were present in feces, sera and nares, but the animals did not manifest signs of clinical disease (Meng et al 1998a). Injection of SPF pigs with human HEV strains of Asia-Africa or Mexico genotypes did not lead to infection (Meng et al 1998a), whereas injection of SPF pigs with United States human HEV did lead to infection (Meng et al 1998b). The HEV isolated from the pigs were identified as United States human HEV.

Injection of rhesus monkeys with United States swine HEV led to seroconversion, fecal shedding of virus and viremia. There was mild acute hepatitis with a slight elevation of liver enzyme activity (Meng et al 1998b). A chimpanzee injected with swine HEV seroconverted and shed virus in feces, but did not show viremia or signs of hepatitis. Virus isolated from the feces of the infected primates were sequenced and confirmed as United States swine HEV (Meng et al 1998b). The fact that non-human primates could be infected by swine HEV strongly suggests that swine HEV can infect humans, and that swine are a reservoir for HEV.

A survey of pigs from herds in Taiwan indicated that 37% were positive for anti-HEV IgG (Hsieh et al 1999). The nucleotide sequence of Taiwan swine HEV had only 80% identity with United States swine HEV. The Taiwan swine HEV had 97% nucleotide identity to Taiwan human HEV, but only 70-77% identity to human HEV of the Asia-Africa, Mexico, or United States genotypes. The preliminary data obtained by Meng et al (1997) and Hsieh et al (1999) indicates that swine and human isolates from a particular geographical area are closely related. The close genetic relationship of the swine HEV and human HEV isolates from Taiwan has led Hsieh et al (1999) to postulate that pigs are a source of sporadic hepatitis E in people in Taiwan.

Further studies indicate that pigs from China and Thailand, HEV endemic countries, had a HEV seropositivity of about 30% (Meng et al 1999). The HEV seropositivity for pigs from countries not endemic for HEV, such as Australia, Canada and Korea, ranged from 4-41% (Meng et al 1999; Chandler et al 1999). These preliminary data indicate that HEV seropositivity is present in pigs in both HEV endemic and non-endemic countries. Thus, the presence of anti-HEV IgG in pigs from various parts of the world indicates that pigs are a probable reservoir of the virus.

Implications of swine HEV

The fecal excretion of HEV by infected pigs when considered in light of the relatedness of human and swine HEV strains indicates that various scenarios exist that could lead to the spread of HEV in the environment. For example, run-off waters from pig farms or from lands spread with untreated pig manure could pollute irrigation and surface waters and result in the eventual contamination of fruits and vegetables. Also, run-off water from swine farms could pollute water environments in which shellfish are growing with resultant contamination of the shellfish with HEV. Thus, the ubiquity of swine production coupled with the increased globalization of the food marketplace has important implications in the spread of hepatitis E.


  1. Aggarwal, R. and S. R. Naik. 1997. Epidemiology of hepatitis E: past, present and future. Trop. Gastroenterol. 18: 49-56.
  2. Chandler, J. D., M. A. Riddell, F. Li, R. J. Love and D. A. Anderson. 1999. Serological evidence for swine hepatitis E virus infection in Australian pig herds. Vet. Microbiol. 68: 95-105.
  3. Chauhan, A., J. B. Dilawari, U. Kaur, S. Jameel, Y. K. Chawla and N. K. Ganguly. 1993. Hepatitis E virus transmission to a volunteer. Lancet 341: 149-150.
  4. Erker, J. C., S. M. Desai, G. C. Schlauder, G. J. Dawson and I. K. Mushahwar. 1999. A hepatitis E variant from the United States: Molecular characterization and transmission in cynomolgus macaques. J. Gen. Virol. 80: 681-690. 
  5. Favorov, M. O. and H. S. Margolis. 1999. Hepatitis E virus infection: an enterically transmitted cause of hepatitis, 1-16. In W. M. Schied, W. A. Craig and J. M. Hughes (eds.), Emerging Infections 3, ASM Press, Washington, DC. 
  6. Hsieh, S. Y., J. J. Meng, Y. H. Wu, S. T. Liu, A. W. Tam, D. Y. Lin and Y. T. Liaw. 1999. Identity of a novel swine hepatitis E virus in Taiwan forming a monophyletic group with Taiwan isolates of human hepatitis E virus. J. Clin. Microbiol. 37: 3828-3834.
  7. Khuroo, M. S. and M. Y. Dar. 1992. Hepatitis E: Evidence for person-to-person transmission and inability of low dose immune serum globulin from an Indian source to prevent it. Indian J. Gastroenterol. 11: 113-116.
  8. Khuroo, M. S., M. R. Tell, S. Skidmore, M. A. Sofi and M. I. Khuroo. 1981. Incidence and severity of viral hepatitis in pregnancy. Am. J. Med. 70: 252-255. 
  9. Labrique, A. B., D. L. Thomas, S. K. Stoszek and K. E. Nelson. 1999. Hepatitis E: An emerging infectious disease. Epidemiol. Rev. 21: 162-179.
  10. Langer, R. C. A. and G. G. Frösner. 1996. Relative importance of the enterically transmitted human hepatitis viruses type A and E as a cause of foreign travel associated hepatitis. Arch. Virol. (Suppl) 11: 171-179.
  11. Mast, E. E. and K. Krawczynski. 1996. Hepatitis E: An overview. Ann. Rev. Med. 47: 257-266.
  12. McCrudden, R., S. O'Connell, T. Farrant, S. Beaton, J. P. Iredale and D. Fine. 2000. Sporadic acute hepatitis E in the United Kingdom: An underdiagnosed phenomenon? Gut 46: 732-733.
  13. Meng, X.-J., S. Dea, R. E. Engle, R. Friendship, Y. S. Lyoo, T. Sirinarumitr, K. Urairong, D. Wang, D. Wong, D. Yoo, Y. Zhang, R. H. Purcell and S. U. Emerson. 1999. Prevalence of antibodies to the hepatitis E virus in pigs from countries where hepatitis E is common or is rare in the human population. J. Med. Virol. 59: 297-202. 
  14. Meng, X-J., P. G. Halbur, J. S. Haynes, T. S. Tsarera, J. D. Bruna, R. L. Royer. R. H. Purcell and S. U. Emerson. 1998a. Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch. Virol. 143: 1405-1415.
  15. Meng, X-J., P. G. Halbur, M. S. Shapiro, S. Govindarajan, J. D. Bruna, I. K. Mushahwar, R. M. Purcell, and S. U. Emerson. 1998b. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J. Virol. 72: 9714-9721.
  16. Meng, X-J., R. H. Purcell, P. G. Halbur, J. R. Lehman, D. M. Webb, T. S. Tsarveva, J. S. Haynes, B. J. Thacker and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E virus. Proc. Natl. Acad. Sci. USA 94: 9860-9865.
  17. Robson, S. C., S. Adams, N. Brink, B. Woodruff and D. Bradley. 1992. Hospital outbreak of hepatitis E. Lancet 339: 1424-1425.
  18. Schlauder, G. G., S. M. Desai, A. R. Zanetti, N. C. Tassopoulos and I. K. Mushabwar. 1999. Novel hepatitis E virus (HEV) isolates from Europe: Evidence for additional genotypes of HEV. J. Med. Virol. 57: 243-251. 
  19. Schlauder, G. G., G. J. Dawson, J. C. Erker, P. Y. Kwo, M. F. Knigge, D. L. Smalley, J. E. Rosenblatt, S. M. Desai and I. K. Mushahwar. 1998. The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. J. Gen. Virol. 79: 447-456.
  20. Ticehurst, J. 1995. Hepatitis E virus, p. 1056-1067. In P. R. Murray (ed.), Manual of clinical microbiology, 6th ed., ASM Press, Washington, DC, USA.
  21. Tsang, T. H. F., E. K. Denison, H. V. Williams, L. V. Venczel, M. M. Ginsberg and D. J. Vugia. 2000. Acute hepatitis E infection acquired in California. Clin. Infect. Dis. 30: 618-619.
  22. Tsarev, S. A., L. N. Binn, P. J. Gomatos, R. R. Arthur, M. K. Monier, H. van Cryck-Gandre, C. F. Longer and B. L. Innis. 1999. Phylogenetic analysis of hepatitis E virus isolates from Egypt. J. Med. Virol. 57: 68-74.
  23. Tsega, E. K. Krawczynski, B.-G. Hansson and E. Nordenfelt. 1993. Hepatitis E virus detection in pregnancy in Ethiopia. Ethiop. Med. J. 31: 173-181. 
  24. Yarbough, P. O. 1999. Hepatitis E virus. Intervirology 42: 179-184.

Feedback about this article or suggestions about topics that you would like us to address should be addressed to either the author of this article or the editor, below.

Author: James L. Smith, Ph.D. (
Editor: Mark L. Tamplin, Ph.D.

Last Modified: 10/24/2006
Footer Content Back to Top of Page