Hepatitis E is an enterically transmitted infection that is typically self-limited. It is caused by the hepatitis E virus (HEV) and is spread by fecally contaminated water within endemic areas. Outbreaks can be epidemic and individual. Hepatitis E has many similarities with hepatitis A. Hepatitis E has been associated with chronic hepatitis in solid organ-transplant recipients.
The course of infection has 2 phases, the prodromal phase and the icteric phase. The infection is self-limited. Whether protective immunoglobulins develop against future reinfection remains unknown. The overall case fatality rate is 4%, though pregnant women and liver transplant recipients may be at substantially higher risk.
Therapy should be predominantly preventive, relying on clean drinking water, good sanitation, and proper personal hygiene. A successful recombinant hepatitis E vaccine has been developed.
Epidemiology
Classification
There is only one serotype of the virus and classification is based on the nucleotide sequences of the genome. Genotype 1 has been classified into five subtypes. The number of genotype 2 can be classified into two subtypes. Genotypes 3 and 4 have been into ten and seven subtypes respectively.
Distribution
Genotype 1 has been isolated from tropical and several subtropical countries in Asia and Africa. Genotype 2 has been isolated from Mexico, Nigeria, and Chad.
Genotype 3 has been isolated almost worldwide including Asia, Europe, Oceania, North and South America. Genotype 4 appears to be limited exclusively to Asia.
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.
Clinical features
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%.
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.
In immunocompromised subjects - particularly in solid organ transplanted patients - Hepatitis E may cause a chronic infection. Occasionally this may cause liver fibrosis and cirrhosis. The use of low dose ribavirin (600 to 800 milligrams / day) over a three month period has been associated with viral clearance in such cases.
Transmission
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.
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.
A different vaccine (HEV 239, sold as Hecolin by its developer Xiamen Innovax Biotech) was approved for the disease in 2012 by the Chinese Ministry of Science and Technology, following a phase 3 trial on two groups of 50,000 people each from Jiangsu Province where none of the vaccinated became infected during a 12 month period, compared to 15 in the group given placebo treatment.
