Hepatitis E: So What’s New?

Abstracts & Commentary

Synopsis: Recent cases of hepatitis E in Europe demonstrate that this illness is not limited to developing countries with limited hygiene. An outbreak in Pakistan shows that secondary person-to-person spread is unusual despite primary attack rates of approximately 15% in young adults.

Sources: Widdowson M-A, et al. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in The Netherlands. Clin Infect Dis. 2003;36:29-33; Bryan JP, et al. Epidemic of hepatitis E in a military unit in Abbottabad, Pakistan. Am J Trop Med Hyg. 2002;67:662-668.

Three unrelated octogenarians living within 10 miles of each other in The Netherlands developed acute hepatitis over a 6-month period. Each patient showed serologic evidence of hepatitis E antibodies. The patients had no known contact with each other or with other individuals who had hepatitis. There had been no recent foreign travel and any unusual food or water exposure. Hepatitis E virus was isolated from one of the patients; genetic sequencing showed that it was similar both to European and North American strains of hepatitis E and to strains of hepatitis E found in Dutch pigs. The patients recovered within 2 months of the onset of their illnesses.

In Pakistan, 109 men were hospitalized with acute hepatitis. At the time of presentation, anti-hepatitis E IgM was identified in 91% of those with sequentially obtained blood samples; only 14% still showed specific IgM antibodies 4 months later. The hepatitis outbreak was linked to fecal contamination of the water system.

Comment by Philip R. Fisher, MD, DTM&H

A viral etiology for "enterically transmitted non-A, non-B hepatitis" was identified in 1983. The inciting agent was referred to as hepatitis E when the illness was increasingly appreciated as an emerging infection. This illness was not actually new, since retrospective testing revealed there had been a large outbreak of this illness in India in the 1950s. The hepatitis E virus was eventually cloned and sequenced in the early 1990s.

Three years ago, Travel Medicine Advisor Update reviewed new clinical information about hepatitis E. Then, as now, it is understood that hepatitis E results from infection by a single-stranded RNA virus that is transmitted by the fecal-oral route. Infection is most common in young adults with attack rates that are highest in women during the second and third trimesters of pregnancy. The disease is self-limited without demonstrated chronic persistence of infection, but the mortality rate is high during pregnancy. Asymptomatic infections are commonly seen, as is the case with hepatitis A. Travelers, especially those to the Indian subcontinent, seemed to be particularly at risk with some evidence that approximately 1% of foreign travelers became infected.

In recent years, genetic sequencing has identified several related genotypes of the hepatitis E virus. One is found in India and surrounding countries. Another is found predominantly in Mexico. A third is found in both North America and Europe as well as in swine populations. A fourth is found in China. The virus identified during the recent cluster of cases in The Netherlands was of the third genotype. The means of transmission to these 3 patients is unknown, but approximately 22% of Dutch swineherds are infected with similar hepatitis E strains. In the United States, wild rodents are often seropositive for hepatitis E virus antibodies.

Seroprevalence studies for hepatitis E are plagued by varying antibody detection techniques and uncertain reproducibility. Nonetheless, studies show that only about 5% of children are infected during the first decade of life and that seroprevalence rises to 10-40% after age 25 years. With acute infection, IgM antibody levels decline rapidly, usually within 4 months, and IgG antibody levels remain elevated for at least 4 years. In the Pakistani military epidemic, approximately 30% of the men tested seemed to have pre-existing anti-hepatitis E antibodies; these antibodies seemed to protect against infection during the outbreak. Vaccine studies are in progress.

In the Pakistani epidemic, 13% of soldiers, including 19% of those who were seronegative at the onset of the outbreak, developed infection. The incubation period for this infection was 2-10 weeks. Four contacts of the original cases developed infection, but they did so with a timing that suggested that a shared single-point exposure might have caused all the cases. Later additional cases were not seen in the military unit. Thus, secondary person-to-person spread seems much less common for hepatitis E than for hepatitis A viruses.

Twenty years after the discovery of hepatitis E, we know that this infection is not limited to developing countries or tropical climates. Transmission is usually linked to contaminated food or water rather than to direct person-to-person spread. Travelers, especially young adult men and pregnant women visiting the Indian subcontinent, should remain vigilant about food and water hygiene.

Recommended Reading

1. Fischer PR. Hepatitis E: Synopsis of recent publications and presentations. Travel Medicine Advisor Update. 2000;10:1-2.

2. Krawczynski K, et al. Hepatitis E. Infect Dis Clin North Am. 2000;14:669-687.

3. Wolk DM, et al. Laboratory diagnosis of viral hepatitis. Infect Dis Clin North Am. 2001;15:1109-1126.