Hepatitis E
Encyclopedia
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.
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 frame
s (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
.
(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.
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).
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 chicken
s. 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 node
s, colon
and liver
of experimentally infected pig
s.
n 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.
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.
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(liver inflammation) caused by infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
with a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
called hepatitis E virus
Hepatitis E virus
Hepatitis E virus is the infective organism that causes hepatitis E.The viral particles are 27 to 34 nanometers in diameter, are non-enveloped and contain a single-strand of positive-sense RNA that is approximately 7300 bases in length. The virus particle was first visualised in 1983 but was only...
(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
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
viruses: A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
, B, C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
, D
Hepatitis D
Hepatitis D, also referred to as hepatitis D virus and classified as Hepatitis delta virus, is a disease caused by a small circular enveloped RNA virus. It is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a subviral satellite because it can propagate only in the...
, and E. Infection with this virus was first documented in 1955 during an outbreak in New Delhi
New Delhi
New Delhi is the capital city of India. It serves as the centre of the Government of India and the Government of the National Capital Territory of Delhi. New Delhi is situated within the metropolis of Delhi. It is one of the nine districts of Delhi Union Territory. The total area of the city is...
, India.
Molecular biology
Although it was originally classified in the CaliciviridaeCaliciviridae
The Caliciviridae family are a family of viruses, members of Class IV of the Baltimore scheme. They are positive-sense, single stranded RNA which is non-segmented. The caliciviruses have been found in a number of organisms such as humans, cattle, pigs, cats, chickens, reptiles, dolphins and...
family, the virus has since been classified into the genus Hepevirus
Hepevirus
Hepevirus is a viral genus with no currently assigned family. This genus is not to be confused with the Herpesvirus family. Hepevirus is a fairly isolated viral genus in which the virions are characterized by round, non-enveloped and isometric capsids with a diameter of 27-34 nm. The gene is...
, 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 frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
s (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encode a methyltransferase
Methyltransferase
A methyltransferase is a type of transferase enzyme that transfers a methyl group from a donor to an acceptor.Methylation often occurs on nucleic bases in DNA or amino acids in protein structures...
, protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, helicase
Helicase
Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
and replicase; ORF2 encode the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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
GenBank
The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. This database is produced and maintained by the National Center for Biotechnology Information as part of the International Nucleotide Sequence...
.
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 infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
(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
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
disease, and is fatal in about 2% of all cases. Clinically
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, it is comparable to hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
, 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
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
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
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
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 contaminationFeces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
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
New Delhi
New Delhi is the capital city of India. It serves as the centre of the Government of India and the Government of the National Capital Territory of Delhi. New Delhi is situated within the metropolis of Delhi. It is one of the nine districts of Delhi Union Territory. The total area of the city is...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
(30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir
Kashmir
Kashmir is the northwestern region of the Indian subcontinent. Until the mid-19th century, the term Kashmir geographically denoted only the valley between the Great Himalayas and the Pir Panjal mountain range...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
(52,000 cases in 1978), Kanpur, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
(79,000 cases in 1991), and China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
(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
Suncus murinus
The Asian House Shrew , or the Asian Musk Shrew, is a widespread, adaptable species of shrew found mainly in South Asia but introduced widely throughout Asia....
). 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 chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
s. 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
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s, colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
of experimentally infected pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s.
Recent outbreaks
In 2004, there were two major outbreaks, both of them in sub-SaharaSahara
The Sahara is the world's second largest desert, after Antarctica. At over , it covers most of Northern Africa, making it almost as large as Europe or the United States. The Sahara stretches from the Red Sea, including parts of the Mediterranean coasts, to the outskirts of the Atlantic Ocean...
n Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
. There was an outbreak in Chad
Chad
Chad , officially known as the Republic of Chad, is a landlocked country in Central Africa. It is bordered by Libya to the north, Sudan to the east, the Central African Republic to the south, Cameroon and Nigeria to the southwest, and Niger to the west...
in which, as of September 27, there were 1,442 reported cases and 46 deaths. The second was in Sudan
Sudan
Sudan , officially the Republic of the Sudan , is a country in North Africa, sometimes considered part of the Middle East politically. It is bordered by Egypt to the north, the Red Sea to the northeast, Eritrea and Ethiopia to the east, South Sudan to the south, the Central African Republic to the...
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 sanitationSanitation
Sanitation is the hygienic means of promoting health through prevention of human contact with the hazards of wastes. Hazards can be either physical, microbiological, biological or chemical agents of disease. Wastes that can cause health problems are human and animal feces, solid wastes, domestic...
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.