Hepatitis E virus (HEV), the major etiologic agent of enterically transmitted non-A, non-B hepatitis worldwide, is a spherical, non-enveloped, single stranded RNA virus that is approximately 32 to 34 nm in diameter. Based on similar physicochemical and biologic properties, HEV has been provisionally classified in the Caliciviridae family; however, the organization of the HEV genome is substantially different from that of other caliciviruses and HEV may eventually be classified in a separate family.
Hepatitis E - Clinical Features.
Average 40 days
Range 15-60 days
Pregnant women, 15%-25%
Increased with age
The incubation period following exposure to HEV ranges from 15 to 60 days (mean, 40 days). Typical clinical signs and symptoms of acute hepatitis E are similar to those of other types of viral hepatitis and include abdominal pain anorexia, dark urine, fever, hepatomegaly, jaundice, malaise, nausea, and vomiting. Other less common symptoms include arthralgia, diarrhea, pruritus, and urticarial rash. The period of infectivity following acute infection has not been determined but virus excretion in stools has been demonstrated up to 14 days after illness onset. In most hepatitis E outbreaks, the highest rates of clinically evident disease have been in young to middle-age adults; lower disease rates in younger age groups may be the result of an icteric and/or subclinical HEV infection. No evidence of chronic infection has been detected in long-term follow-up of patients with hepatitis E.
The typical serologic course following HEV infection has been characterized using experimental models of infection in nonhuman primates and human volunteer studies. In two human volunteer studies, liver enzyme elevations occurred 4-5 weeks after oral ingestion and persisted for 20-90 days. Virus excretion in stools occurred approximately 4 weeks after oral ingestion and persisted for about 2 weeks. Both IgM and IgG antibody to HEV (anti-HEV) are elicited following HEV infection. The titer of IgM anti-HEV declines rapidly during early convalescence; IgG anti-HEV persists and appears to provide at least short-term protection against disease. No serologic tests to diagnose HEV infection are commercially available in the United States. However, several diagnostic tests are available in research laboratories, including enzyme immunoassays and Western blot assays to detect IgM and IgG anti-HEV in serum, polymerase chain reaction tests to detect HEV RNA in serum and stool, and immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver.
Hepatitis E - Epidemiologic Features.
HEV is transmitted primarily by the fecal-oral route and fecally contaminated drinking water is the most commonly documented vehicle of transmission. Although hepatitis E is most commonly recognized to occur in large outbreaks, HEV infection accounts for >50% of acute sporadic hepatitis in both children and adults in some high endemic areas. Risk factors for infection among persons with sporadic cases of hepatitis E have not been defined. Unlike hepatitis A virus, which is also transmitted by the fecal-oral route, person-to-person transmission of HEV appears to be uncommon. However, nosocomial transmission, presumably by person-to-person contact, has been reported to occur. Virtually all cases of acute hepatitis E in the United States have been reported among travelers returning from high HEV-endemic areas.
Outbreaks of hepatitis E have occurred over a wide geographic area, primarily in developing countries with inadequate environmental sanitation. The reservoir of HEV in these areas is unknown. The occurrence of sporadic HEV infections in humans may maintain transmission during inter-epidemic periods, but a nonhuman reservoir for HEV is also possible. In the United States and other non-endemic areas, where outbreaks of hepatitis E have not been documented to occur, a low prevalence of anti-HEV (less than 2%) has been found in healthy populations. The source of infection for these persons is unknown.
Prevention and Control Measures for Travelers to HEV-Endemic Regions.
Prevention of hepatitis E relies primarily on the provision of clean water supplies. Prudent hygienic practices that may prevent hepatitis E and other enterically transmitted diseases among travelers to developing countries include avoiding drinking water (and beverages with ice) of unknown purity, uncooked shellfish, and uncooked fruits or vegetables that are not peeled or prepared by the traveler. No products are available to prevent hepatitis E. IG prepared from plasma collected in non-HEV-endemic areas is not effective in preventing clinical disease during hepatitis E outbreaks and the efficacy of IG prepared from plasma collected in HEV-endemic areas is unclear. In studies conducted to date with prototype vaccines in animals, vaccine-induced antibody attenuated HEV infection, but did not prevent virus excretion in stools. If a vaccine is developed, the epidemiology of hepatitis E needs to be further defined in order to determine whether vaccination strategies could be effectively used to prevent this disease.