Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with a virus called hepatitis E virus (HEV). HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kilobase genome. HEV has a fecal-oral transmission route. It is one of five known hepatitis viruses: A, B, C, D, and E. Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India.
Molecular Biology
Although it was originally classified in the Caliciviridae family, the virus has since been classified into the genus Hepevirus, but was not assigned to a viral family. The virus itself is a small non-enveloped particle.
The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase, protease, helicase and replicase; ORF2 encode the capsid protein and ORF3 encodes a protein of undefined function. A three-dimensional, atomic-resolution structure of the capsid protein in the context of a virus-like particle has been described. An in vitro culture system is not yet available.
As of 2009 there are approximately 1,600 sequences of both human and animal isolates of HEV available in open-access sequence databases.
Epidemiology
The incidence of hepatitis E is highest in juveniles and adults between the ages of 15 and 40. Though children often contract this infection as well, they less frequently become symptomatic. Mortality rates are generally low, for hepatitis E is a “self-limiting” disease, in that it usually goes away by itself and the patient recovers. However, during the duration of the infection (usually several weeks), the disease severely impairs a person’s ability to work, care for family members, and obtain food. Hepatitis E occasionally develops into an acute, severe liver disease, and is fatal in about 2% of all cases. Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more often severe and is associated with a clinical syndrome called fulminant hepatic failure. Pregnant women, especially those in the third trimester, suffer an elevated mortality rate from the disease of around 20%.
Although there is one serotype of this virus, four distinct genotypes have been reported. Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries.
Differences have been noted between the different genotypes. For genotype 1, the age at which incidence peaks is between 15 and 35 years and mortality is about 1%. Genotype 3 and 4 — the most common in Japan — are more common in people older than 60 years and the mortality is between 5 and 10%. Although prednisolone has been used in the treatment of this condition, because large scale studies have not yet been reported, the role of this drug in treatment is not yet clear.
Patterns
Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate. It is widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly through fecal contamination of water supplies or food; person-to-person transmission is uncommon. Outbreaks of epidemic hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies. Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).
Animals as a reservoir
Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are, however, still unclear.
A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat (Bandicota bengalensis), the black rat (Rattus rattus brunneusculus) and the Asian house shrew (Suncus murinus). A new virus designated rat hepatitis E virus has been isolated.
An avian virus has been described that is associated with hepatitis-splenomegaly syndrome in chickens. This virus is genetically and antigenically related to mammalian HEV, and probably represents a new genus in the family.
Replicative virus has been found in the small intestine, lymph nodes, colon and liver of experimentally infected pigs.
Recent outbreaks
In 2004, there were two major outbreaks, both of them in sub-Saharan Africa. There was an outbreak in Chad in which, as of September 27, there were 1,442 reported cases and 46 deaths. The second was in Sudan with, as of September 28, 6,861 cases and 87 deaths. Increasingly, hepatitis E is being seen in developed nations, with reports of cases in the UK, US and Japan. The disease is thought to be a zoonosis in that animals are thought to be the source. Both deer and swine have been implicated.
In 2011, a minor outbreak was reported in Tangail, a neighborhood of Dhaka, Bangladesh.
In June 2011, in Mumbai, six pregnant women died due to hepatitis E.
Prevention
Improving sanitation is the most important measure, which consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many others that plague developing nations, and they require large-scale international financing of water supply and water treatment projects. A vaccine based on recombinant viral proteins has been developed and recently tested in a high-risk population (military personnel of a developing country). The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost-effectiveness of hepatitis E vaccination.