Laboratory-based Surveillance for Hepatitis E Virus Infection, United States, 2005–2012

Jan Drobeniuc

, Tracy Greene-Montfort, Ngoc-Thao Le, Tonya R. Mixson-Hayden, Lilia Ganova-Raeva, Chen Dong, Ryan T. Novak, Umid M. Sharapov, Rania A. Tohme, Eyasu Teshale, Saleem Kamili, and Chong-Gee Teo

Author affiliations: Author affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA

Abstract

To investigate characteristics of hepatitis E cases in the United States, we tested samples from persons seronegative for acute hepatitis A and B whose clinical specimens were referred to the Centers for Disease Control and Prevention during June 2005–March 2012 for hepatitis E virus (HEV) testing. We found that 26 (17%) of 154 persons tested had hepatitis E. Of these, 15 had not recently traveled abroad (nontravelers), and 11 had (travelers). Compared with travelers, nontravelers were older (median 61 vs. 32 years of age) and more likely to be anicteric (53% vs. 8%); the nontraveler group also had fewer persons of South Asian ethnicity (7% vs. 73%) and more solid-organ transplant recipients (47% vs. 0). HEV genotype 3 was characterized from 8 nontravelers and genotypes 1 or 4 from 4 travelers. Clinicians should consider HEV infection in the differential diagnosis of hepatitis, regardless of patient travel history.

Hepatitis E in Africa, southern and central Asia, and Central America causes occasional outbreaks of jaundice and, between outbreaks, occurrences of sporadic jaundice. Primarily spread by waterborne transmission, the disease tends to resolve spontaneously, although fulminant hepatic failure can ensue (1). In eastern Asia and Europe, sporadic hepatitis E, whether imported after return from international travel or acquired indigenously, has been observed; the indigenous form is thought to be foodborne (2). Although the disease is largely self-limiting, in Europe, chronic hepatitis E, which may lead to cirrhosis, is increasingly recognized among solid-organ transplant recipients (SOTRs) (3).
The causative agent of hepatitis E is hepatitis E virus (HEV), of which 4 genotypes are found in humans. Genotypes 1 and 2 circulate in regions where waterborne transmission is common; genotype 3 is prevalent in eastern Asia and the West and genotype 4 in eastern Asia. Genotypes 1 and 2 infect humans, but genotypes 3 and 4 infect humans and animals, predominantly pigs (4).
In the United States, HEV imported into the country after travel to regions to which waterborne HEV transmission is endemic is well recognized (5–7). Recently, 21% of participants of the US-based Third National Health and Nutrition Examination Survey were found seropositive for IgG against HEV (8). This unexpectedly high prevalence rate would not be ascribable to imported HEV infection alone. Indeed, cases of hepatitis E unassociated with travel abroad have been observed in the United States, implying infection by indigenous HEV strains (9–14). Moreover, the increasing number of reports from Europe of hepatitis E among SOTRs (3,15) suggests that SOTRS in the United States might be similarly susceptible to the disease.
We report a study of demographic, clinical, travel-related, and virologic characteristics of persons with hepatitis E derived from a diverse patient base. Critical to this investigation was the application of a validated serologic assay for detecting IgM against HEV (16), the marker of recent HEV infection, as well as a real-time reverse transcription PCR (RT-PCR) that had been validated to detect, to high sensitivity, HEV RNA (17), which is an indicator of active HEV shedding. Together, these 2 assays enabled us to identify patients with incident hepatitis E.