Hepatitis E Virus

Hepatitis E is an important public health disease in many developing countries of Asia and Africa with large explosive outbreaks. The disease is also endemic with sporadic or clustered cases in many industrialized countries. The causative agent, hepatitis E virus (HEV), is a small nonenveloped positive-sense RNA virus that is currently classified in the family Hepeviridae. At least four recognized and two putative genotypes of mammalian HEV have been recognized: genotypes 1 and 2 HEV are restricted to humans and associated with epidemics, whereas genotypes 3 and 4 HEV are zoonotic and associated with sporadic and clustered cases. The life cycle and replication mechanism of HEV remain largely unknown. The genome of HEV consists of three open reading frames (ORF): ORF1 encodes nonstructural proteins involved in virus replication, ORF2 encodes the major capsid protein that induces neutralizing antibodies, and ORF3 encodes a small multifunctional protein. ORF2 and ORF3 overlap each other but neither overlaps ORF1, and the ORF2 and ORF3 proteins are translated from a single bicistronic mRNA. Waterborne transmission of HEV due to fecal contamination of water supplies is the most important route of spread, although other routes such as zoonotic, vertical, foodborne, and blood-borne transmissions have also been documented. In addition to the main clinical signs such as jaundice, anorexia, abdominal pain, nausea, vomiting, and fever, HEV infection has recently been linked to neurological symptoms, although the mechanism of neurotropic clinical manifestation remains unclear. The highest attack rate of clinical disease is in young adults of 20–29 years of age, although the seroprevalence of HEV increases with age. The mortality associated with HEV infection is generally <1 % in the general population, although a relatively high mortality rate of up to 25 % has been reported in infected pregnant women. Hepatitis E was thought to be an exclusively self-limiting acute disease; however, persistent and chronic hepatitis E cases have recently been reported in immunocompromised individuals such as organ transplant recipients. The genetic identification of numerous animal strains of HEV and the demonstrated ability of cross-species infection by these strains have not only broadened our understanding of the ecology and natural history of HEV but also raised important public health concerns for zoonotic HEV transmission and food safety. Pigs and likely other animal species such as deer and rabbits may serve as reservoirs for HEV. Animal handlers such as pig farmers and swine veterinarians have been identified as high-risk occupations and are at an increased risk of zoonotic exposure to HEV infection. The current available diagnostic assays for HEV are not standardized or approved by FDA, and consequently hepatitis E is underdiagnosed in industrialized countries. A vaccine against HEV was recently licensed for use in China, but is not yet available in other countries; protection of water from fecal contamination, practicing good hygiene, and avoiding consumption of raw animal meats are still the primary preventive measures. Pegylated interferon-α and ribavirin have been shown to induce a sustained inhibition of HEV and improve liver histology in infected patients and thus may serve as potential antiviral drugs.