Hepatitis E: A Synopsis of Recent Publications and Presentations

reviews & commentary

By Philip R. Fischer, MD, DTM&H

Synopsis: Hepatitis E is increasingly identified in various areas of the world, and animal reservoirs have been found in the United States. Infection is not rare in travelers, but it is often subclinical.

Hepatitis e virus (hev) is an important cause of acute liver disease in many developing countries. It is felt to be spread by the fecal-oral route, usually causes epidemic illness, and generally affects young adults. Hepatitis E is particularly severe during pregnancy.

A few years ago, a retrospective serosurvey showed that hepatitis E was essentially nonexistent in expatriate American missionaries from 1967-1984.1 Case reports, however, have identified hepatitis E in travelers,2 and a survey of California blood donors (1% seropositive) revealed that foreign travel was a risk factor for HEV seropositivity.3

In recent months, new publications and scientific presentations reveal an expanding knowledge base about hepatitis E. Several of these are intended to keep our readers up-to-date.

Eli Schwartz and colleagues in Israel reported five cases of HEV infection in travelers and reviewed the literature. They identified the Indian subcontinent as the most likely destination of travelers who became infected. (Schwartz E, et al. Hepatitis E virus infection in travelers. Clin Infect Dis 1999;29:1312-1314.)

Beyond case reports identifying the possibility of HEV infection in travelers, however, one wonders how common this illness actually is. Ooi and colleagues from three U.S. travel clinics prospectively evaluated 356 travelers. Interestingly, nine (3%) were already IgG seropositive on entry into the study, and each of these individuals had traveled outside the United States in the preceding five years. New infection was identified in four short-term (8-21 days) travelers (to China, Peru, Russia, and Thailand) even though all four remained asymptomatic. Thus, it appears that new HEV infection can occur in more than 1% of American travelers. Thus, hepatitis E could be similar to hepatitis A in frequency.4 (Ooi WW, et al. Hepatitis E seroconversion in United States travelers abroad. Am J Trop Med Hyg 1999;61: 822-824.)

Meanwhile, epidemics continue to occur. Larasati and colleagues reported to the American Society of Tropical Medicine and Hygiene in Washington, DC, December 1999, about an epidemic in Indonesia that involved more than 500 clinical cases. A full 2% of the population became ill, but 90% of cases occurred in individuals older than 20 years of age. There is, so far, no clear explanation for the apparent sparing of children from hepatitis E during the first two decades of life. (Larasati RP, et al. First time epidemic HEV transmission in Java, Indonesia. Abstract 537. 48th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, DC, 1999.)

Closer to home, HEV is also lurking. Wondering if an animal reservoir might be more important than the postulated fecal-oral transmission, Kabrane-Lazizi and associates tested serum samples from 239 wild rats collected in various U.S. sites. Seropositivity for HEV was found in 44% of rats from Louisiana, 77% of rats from Maryland, and 90% of rats from Hawaii. Further study will be needed to identify the relationship(s) between the high frequency of HEV infection in rats and the apparent non-endemicity of human HEV in the United States. (Kabrane-Lazizi Y, et al. Evidence for widespread infection of wild rats with hepatitis E virus in the United States. Am J Trop Med Hyg 1999;61:331-335.) Pigs have also been suggested to be potential HEV reservoirs.

It seems that the global HEV situation is evolving even as our understanding of clinical hepatitis E grows. Fortunately, preventive intervention is also being developed. At the recent American Society of Tropical Medicine and Hygiene meeting, Shrestha reported a successful HEV vaccine trial. Forty-four Nepalese volunteers received a series of three injections (0, 1, and 6 months) of a recombinant hepatitis E vaccine. Vaccination was well tolerated with no serious adverse reactions. All vaccine recipients showed serological evidence of protection by the end of the study. Larger studies are planned. (Shrestha SK, et al. A safety and immunogenicity study of a recombinant baculovirus expressed hepatitis E vaccine in healthy Nepalese volunteers. Abstract 1089. 48th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, DC, 1999.)

What should travel medicine practitioners do with this new information about hepatitis E? First, we should continue to advise travelers to avoid sources of fecal-oral contamination and to shy away from close, personal contact with wild animals. Second, realizing that more than 1% of travelers might become infected, pretravel consultation, especially for pregnant travelers, should include a careful discussion of risks and risk avoidance so travelers can judiciously plan the timing and itinerary of their travel. (Dr. Fischer is Associate Professor of Pediatrics, Department of Pediatrics & Adolescent Medicine, Mayo Clinic, Rochester, MN.)


1. Smalligan RD, et al. The risk of viral hepatitis A, B, C, and E among North American missionaries. Am J Trop Med Hyg 1995;53:233-236.

2. Hepatitis E among US travelers, 1989-1992. MMWR Morb Mortal Wkly Rep 1993;42:1-4.

3. Mast EE, et al. Prevalence of and risk factors for antibody to hepatitis E virus seroreactivity among blood donors in Northern California. J Infect Dis 1997; 176:34-40.

4. Reid D, Keystone JS. Health risks abroad: General considerations. In: DuPont HL, Steffen R, eds. Textbook of Travel Medicine and Health. Hamilton, Ontario, Canada: BC Decker; 1997:3-9.

Hepatitis E virus:

a. principally affects young adults.

b. occurs only in humans and not in animals.

c. occurs only on the Indian subcontinent.

d. infects less than 0.5% of travelers from the United States.

e. is a less severe illness in pregnant vs. nonpregnant women.