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Hepatitis E is inflammation of the liver caused by
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
with the
hepatitis E virus The hepatitis E virus (HEV) is the causative agent of hepatitis E. It is of the species ''Orthohepevirus A.'' Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. About 15–110 million ind ...
(HEV); it is a type of
viral hepatitis Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...
. Hepatitis E has mainly a fecal-oral transmission route that is similar to
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
, although the viruses are unrelated. In retrospect, the earliest known epidemic of hepatitis E occurred in 1955 in
New Delhi New Delhi (, , ''Naī Dillī'') is the capital of India and a part of the National Capital Territory of Delhi (NCT). New Delhi is the seat of all three branches of the government of India, hosting the Rashtrapati Bhavan, Parliament House ...
, but the virus was not isolated until 1983 by Russian scientists investigating an outbreak in Afghanistan. HEV is a
positive-sense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
, single-stranded, nonenveloped, RNA icosahedral
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
and one of five known human
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
viruses: A, B, C, D, and E. Like hepatitis A, hepatitis E usually follows an acute and self-limiting course of illness (the condition is temporary and the individual recovers) with low death rates in resource-rich areas; however, it can be more severe in pregnant women and people with a
weakened immune system Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
, with substantially higher death rates. In
pregnant women Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, especially in the third trimester, the disease is more often severe and is associated with a clinical syndrome called
fulminant liver failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicat ...
, with death rates around 20%. Whereas pregnant women may have a rapid and severe course,
organ transplant Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...
recipients who receive medications to weaken the immune system and prevent organ rejection can develop a slower and more persistent form called chronic hepatitis E, which is so diagnosed after 3 months of continuous viremia. HEV can be clustered genetically into 8 genotypes, and genotypes 3 and 4 tend to be the ones that cause chronic hepatitis in the immunosuppressed. In 2017, hepatitis E was estimated to affect more than 19 million people. Those most commonly at risk of HEV are men aged 15 to 35 years of age. A preventive vaccine (HEV 239) is approved for use in
China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
.


Signs and symptoms


Acute infection

The average
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...
of hepatitis E is 40 days, ranging from 2 to 8 weeks. After a short prodromal phase symptoms may include
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
, fatigue, and
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
, though most HEV infections are asymptomatic. The symptomatic phase coincides with elevated hepatic
aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...
levels. Viral RNA becomes detectable in stool and blood serum during the incubation period. Serum IgM and IgG
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
against HEV appear just before the onset of clinical symptoms. Recovery leads to virus clearance from the blood, while the virus may persist in stool for much longer. Recovery is also marked by disappearance of IgM antibodies and increase of levels of IgG antibodies.


Chronic infection

While usually lasting weeks and then resolving, in people with weakened immune systems—particularly in people who have had solid organ transplant—hepatitis E may cause a chronic
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
. Occasionally this may result in a life-threatening illness such as fulminant liver failure or liver
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
.


Other organs

Infection with hepatitis E virus can also lead to problems in other organs. For some of these reported conditions such as musculoskeletal or immune-mediated manifestations the relationship is not entirely clear, but for several neurological and blood conditions the relationship appears more consistent: *
Acute pancreatitis Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes in order of frequency include: 1) a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; 2) heavy alcohol use; 3) systemic disea ...
(HEV genotype 1) * Neurological complications (though the mechanism of neurological damage is unknown at this point.) include: Guillain-Barré syndrome (acute limb weakness due to nerve involvement), neuralgic amyotrophy (arm and shoulder weakness, also known as Parsonage-Turner syndrome), acute
transverse myelitis Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is Inflammation, inflamed. The adjective ''wikt:transverse#Adjective, transverse'' implies that the spinal inflammation (myelitis) extends horizontally throughout ...
and acute
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
. *
Glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...
with nephrotic syndrome and/or cryoglobulinemia * Mixed
cryoglobulinemia Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. ...
, where antibodies in the bloodstream react inappropriately at low temperatures * Severe
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
(low platelet count in the blood) which confers an increased risk of dangerous bleeding


Infection in pregnancy

Pregnant women show a more severe course of infection than other populations. Liver failure with mortality rates of 20% to 25% has been reported from outbreaks of genotype 1 and 2 HEV in developing countries. Besides signs of an acute infections, adverse effects on the mother and fetus may include preterm delivery, abortion,
stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
, and neonatal death. The pathological and biological mechanisms behind the adverse outcomes of
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
infections remain largely unclear. Increased
viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...
and influence of hormonal changes on the immune system are currently thought to contribute to worsening the course of infection. Furthermore, studies showing evidence for viral replication in the placenta or reporting the full
viral life cycle Viruses are only able to Replicate (biology), replicate themselves by commandeering the reproductive apparatus of cells and making them reproduce the virus's genetic structure and virion, particles instead. How viruses do this depends mainly on t ...
in placental-derived cells in vitro suggest that the human
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
may be a site of viral replication outside the liver. The primary reason for HEV severity in pregnancy remains enigmatic.


Virology


Classification

HEV is classified into the family ''Hepeviridae'', which is divided in two genera, ''Orthohepevirus'' (all mammalian and avian HEV isolates) and ''Piscihepevirus'' (cutthroat trout HEV). Only one
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...
of the virus is known, and classification is based on the
nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
sequences of the genome.
Genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
1 can be further subclassified into five subtypes, genotype 2 into two subtypes, and genotypes 3 and 4 have been divided into 10 and seven subtypes. Additionally there are genotypes 5, 6, 7 and 8. Rat HEV was first isolated from Norway rats in Germany, and a 2018 CDC article indicated the detection of rat HEV RNA in a transplant recipient.


Distribution

* Genotype 1 has been isolated from tropical and several subtropical countries in
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
and
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
. * Genotype 2 has been isolated from
Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...
,
Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
, and
Chad Chad (; ar, تشاد , ; french: Tchad, ), officially the Republic of Chad, '; ) is a landlocked country at the crossroads of North and Central Africa. It is bordered by Libya to the north, Sudan to the east, the Central African Republic ...
. * Genotype 3 has been isolated almost worldwide including Asia,
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
,
Oceania Oceania (, , ) is a region, geographical region that includes Australasia, Melanesia, Micronesia, and Polynesia. Spanning the Eastern Hemisphere, Eastern and Western Hemisphere, Western hemispheres, Oceania is estimated to have a land area of ...
, and
North North is one of the four compass points or cardinal directions. It is the opposite of south and is perpendicular to east and west. ''North'' is a noun, adjective, or adverb indicating Direction (geometry), direction or geography. Etymology T ...
and
South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...
. * Genotype 4 appears to be limited to Asia and indigenous cases from Europe. 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.


Transmission

image:Hepatitis E Virus in Pork Liver Sausage.jpg, 390px, Hepatitis E virus in pork liver sausage (the arrows in panel A point to the virion, those in B, C & D point to bound gold nanoparticles used in virus detection) Hepatitis E (genotype 1 and, to a lesser extent genotype 2) is endemic and can cause outbreaks in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly by the
fecal–oral route The fecal–oral route (also called the oral–fecal route or orofecal route) describes a particular route of transmission of a disease wherein pathogens in fecal particles pass from one person to the mouth of another person. Main causes of fecal ...
due to contamination of water supplies or food; direct person-to-person transmission is uncommon. In contrast to genotypes 1 and 2, genotypes 3 and 4 cause sporadic cases thought to be contracted zoonotically, from direct contact with animals or indirectly from contaminated water or undercooked meat. Outbreaks of epidemic hepatitis E most commonly occur after heavy rainfalls, especially
monsoons A monsoon () is traditionally a seasonal reversing wind accompanied by corresponding changes in precipitation but is now used to describe seasonal changes in atmospheric circulation and precipitation associated with annual latitudinal oscil ...
because of their disruption of water supplies; heavy flooding can causes sewage to contaminate water supplies. The World Health Organization recommendation for chlorine on HEV inactivation, a free chlorine residual of for 30 min (pH, <8.0) Major outbreaks have occurred in
New Delhi New Delhi (, , ''Naī Dillī'') is the capital of India and a part of the National Capital Territory of Delhi (NCT). New Delhi is the seat of all three branches of the government of India, hosting the Rashtrapati Bhavan, Parliament House ...
, India (30,000 cases in 1955–1956),
Burma Myanmar, ; UK pronunciations: US pronunciations incl. . Note: Wikipedia's IPA conventions require indicating /r/ even in British English although only some British English speakers pronounce r at the end of syllables. As John Wells explai ...
(20,000 cases in 1976–1977), Kashmir, India (52,000 cases in 1978),
Kanpur, India Kanpur or Cawnpore ( /kɑːnˈpʊər/ pronunciation (help·info)) is an industrial city in the central-western part of the state of Uttar Pradesh, India. Founded in 1207, Kanpur became one of the most important commercial and military stations o ...
(79,000 cases in 1991), and China (100,000 cases between 1986 and 1988). According to Rein et al., HEV genotypes 1 and 2 caused some 20.1 million hepatitis E infections, along with 3.4 million cases of symptomatic disease, and 70,000 deaths in 2005; however the aforementioned paper did not estimate the burden of genotypes 3 and 4. According to the Department for Environment, Food and Rural Affairs, evidence indicated the increase in hepatitis E in the U.K. was due to food-borne
zoonoses A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human ...
, citing a study that found in the U.K. that 10% of pork sausages contained the hepatitis E virus. Some research suggests that food must reach a temperature of for 20 minutes to eliminate the risk of infection. The
Animal Health and Veterinary Laboratories Agency The Animal and Plant Health Agency (APHA), formerly known as the Animal Health and Veterinary Laboratories Agency (AHVLA), is an executive agency of the Department for Environment, Food and Rural Affairs (Defra) of the United Kingdom. It was for ...
discovered hepatitis E in almost half of all pigs in Scotland. Hepatitis E infection appeared to be more common in people on hemodialysis, although the specific risk factors for transmission are not clear.


Animal reservoir

Hepatitis E due to genotypes other than 1 and 2 is thought to be a
zoonosis A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
, in that animals are thought to be the primary reservoir; deer and swine have frequently been implicated. Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Replicative virus has been found in the
small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
,
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s, colon, and
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
of experimentally infected
pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus ...
s. Transmission after consumption of
wild boar The wild boar (''Sus scrofa''), also known as the wild swine, common wild pig, Eurasian wild pig, or simply wild pig, is a suid native to much of Eurasia and North Africa, and has been introduced to the Americas and Oceania. The species is ...
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. Other animal reservoirs are possible but unknown at this time A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat (''
Bandicota bengalensis The lesser bandicoot rat, Sindhi rice rat, bengal rat or Indian mole-rat (''Bandicota bengalensis'') is a giant rat of Southern Asia, not related to the true bandicoots which are marsupials. They can be up to 40 cm long (including the tail ...
''), the black rat (''
Rattus rattus The black rat (''Rattus rattus''), also known as the roof rat, ship rat, or house rat, is a common long-tailed rodent of the stereotypical rat genus ''Rattus'', in the subfamily Murinae. It likely originated in the Indian subcontinent, but is n ...
brunneusculus'') and the Asian house shrew (''
Suncus murinus The Asian house shrew (''Suncus murinus'') is a shrew species native to South and Southeast Asia that has been listed as Least Concern on the IUCN Red List since 2008 because of its large population and wide distribution. It has been introduced i ...
''). A new virus designated rat hepatitis E virus has been isolated.


Genomics

HEV has three open reading frames (ORFs) encoding two polyproteins (O1 and O2 protein). ORF2 encodes three
capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...
proteins whereas O1 encodes seven fragments involved in viral replication, among others. The smallest ORF of the HEV genome, ORF3 is translated from a subgenomic RNA into O3, a protein of 113–115 amino acids. ORF3 is proposed to play critical roles in immune evasion by HEV. Previous studies showed that ORF3 is bound to viral particles found in patient sera and produced in cell culture. Although in cultured cells ORF3 has not appeared essential for HEV RNA replication, viral assembly, or infection, it is required for particle release. 100px, Geldanamycin


Virus lifecycle

The lifecycle of hepatitis E virus is unknown; the capsid protein obtains viral entry by binding to a cellular receptor. ORF2 (c-terminal) moderates viral entry by binding to
HSC70 Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in humans is encoded by the ''HSPA8'' gene on chromosome 11. As a member of the heat shock protein 70 family and a chaperon ...
.
Geldanamycin Geldanamycin is a 1,4-benzoquinone ansamycin antitumor antibiotic that inhibits the function of Hsp90 (Heat Shock Protein 90) by binding to the unusual ADP/ATP-binding pocket of the protein. HSP90 client proteins play important roles in the regula ...
blocks the transport of HEV239 capsid protein, but not the binding/entry of the truncated capsid protein, which indicates that
Hsp90 Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
plays an important part in HEV transport.


Diagnosis

In terms of the diagnosis of hepatitis E, only a laboratory blood test that confirms the presence of HEV RNA or IgM antibodies to HEV can be trusted. In the United States no serologic tests for diagnosis of HEV infection have ever been authorized by the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
has developed an international standard strain for detection and quantification of HEV RNA. In acute infection the viremic window for detection of HEV RNA closes 3 weeks after symptoms begin.


Virological markers

Assuming that vaccination has not occurred, tests may show: * if the person's ''immune system is normal'', then ** if IgM anti-HEV is negative, then there is no evidence of recent HEV infection ** if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection * if the person's ''immune system is weakened by disease or medical treatment'', as in the case of a person who has received a solid organ transplant, then ** if IgM anti-HEV is negative, then if additional blood testing reveals *** positive HEV RNA then the person has HEV infection *** negative HEV RNA then there is no evidence of current or recent infection ** if IgM anti-HEV is positive, then the person is likely to have a recent or current HEV infection, and HEV RNA may be useful to track resolution


Prevention


Sanitation

Sanitation Sanitation refers to public health conditions related to clean drinking water and treatment and disposal of human excreta and sewage. Preventing human contact with feces is part of sanitation, as is hand washing with soap. Sanitation systems ...
is the most important measure in prevention of hepatitis E; this 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 other diseases that plague developing nations. Cooking meat at for five minutes kills the hepatitis E virus, different temperatures means different time to inactivate the virus.


Blood products

The amount of virus present in blood products required to cause transfusion-transmitted infection (TTI) appears variable. Transfusion transmission of hepatitis E virus can be screened via minipool HEV NAT (Nucleic acid testing) screening. NAT is a technique used to screen blood molecularly, when blood donations are received; it screens for TTI.


Vaccines

A vaccine based on recombinant viral proteins was developed in the 1990s and tested in a high-risk population (in
Nepal Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne, सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...
) in 2001. The vaccine appeared to be effective and safe, but development was stopped for lack of profitability, since hepatitis E is rare in developed countries. No hepatitis E vaccine is licensed for use in the United States. The exception is China; after more than a year of scrutiny and inspection by China's State Food and Drug Administration (SFDA), a hepatitis E vaccine developed by Chinese scientists was available at the end of 2012. The vaccine—called HEV 239 by its developer Xiamen Innovax Biotech—was approved for prevention of hepatitis E in 2012 by the Chinese Ministry of Science and Technology, following a controlled trial on 100,000+ people from
Jiangsu Province Jiangsu (; ; pinyin: Jiāngsū, alternatively romanized as Kiangsu or Chiangsu) is an eastern coastal province of the People's Republic of China. It is one of the leading provinces in finance, education, technology, and tourism, with its ca ...
where none of those vaccinated became infected during a 12-month period, compared to 15 in the group given placebo. The first vaccine batches came out of Innovax's factory in late October 2012, to be sold to Chinese distributors. Due to lack of evidence, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
has not made a recommendation regarding routine use of the HEV 239 vaccine as of 2015. Its 2015 position was that national authorities may decide to use the vaccine based on their local epidemiology.


Treatment

There is no drug that has established safety and effectiveness for hepatitis E, and there have been no large randomized clinical trials of antiviral drugs. Reviews of existing small studies suggest that
ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pegin ...
can be considered effective in immunocompromised people who have developed chronic infection. Chronic HEV infection is associated with immunosuppressive therapies, and when that happens in individuals with solid-
organ transplantation Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
, reducing
immunosuppressive Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
medications can result in clearance of HEV in one third of patients.


Epidemiology

The hepatitis E virus causes around 20 million infections a year. These result in around three million acute illnesses and resulted in 44,000 deaths during 2015. Pregnant women are particularly at risk of complications due to HEV infection, who can develop an acute form of the disease that is fatal in 30% of cases or more. HEV is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Hepatitis E is
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found elsew ...
in Central Asia, while Central America and the Middle East have reported outbreaks. Increasingly, hepatitis E is being seen in developed nations, with reports in 2015 of 848 cases of hepatitis E virus infection in England and Wales.


Recent outbreaks

In October 2007, an epidemic of hepatitis E occurred in
Kitgum Kitgum is a municipality in Kitgum District in the Northern Region of Uganda. The town is administered by Kitgum Municipality Council, an urban local government. It is the largest metropolitan area in the district and the site of the district ...
District of northern Uganda. This outbreak progressed to become one of the largest known hepatitis E outbreaks in the world. By June 2009, it had resulted in illness in 10,196 persons and 160 deaths. The aforementioned outbreak occurred despite no previous epidemics having been documented in the country, women were the most affected by HEV. 200px, Namibia, Africa In July 2012, an outbreak was reported in South Sudanese refugee camps in
Maban County Greater Maban (which means ''the people of the land'') is a county located in the Upper Nile State of South Sudan. The county capital is the town of Bunj. In 2017, the South Sudan government divided the county into two: North East and South West. ...
near the
Sudan Sudan ( or ; ar, السودان, as-Sūdān, officially the Republic of the Sudan ( ar, جمهورية السودان, link=no, Jumhūriyyat as-Sūdān), is a country in Northeast Africa. It shares borders with the Central African Republic t ...
border.
South Sudan South Sudan (; din, Paguot Thudän), officially the Republic of South Sudan ( din, Paankɔc Cuëny Thudän), is a landlocked country in East Africa. It is bordered by Ethiopia, Sudan, Central African Republic, Democratic Republic of the C ...
's Ministry of Health reported over 400 cases and 16 fatalities as of 13 September 2012. Progressing further, as of 2 February 2013, 88 died due to the outbreak. The medical charity Medecins Sans Frontieres said it treated almost 4000 people. In April 2014, an outbreak in the Biratnagar Municipality of
Nepal Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne, सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...
resulted in infection of over 6000 locals and at least 9 dead. During an outbreak in
Namibia Namibia (, ), officially the Republic of Namibia, is a country in Southern Africa. Its western border is the Atlantic Ocean. It shares land borders with Zambia and Angola to the north, Botswana to the east and South Africa to the south and ea ...
, the number of affected people rose from 490 in January 2018, to 5014 (with 42 deaths) by April 2019, to 6151 cases (with 56 deaths) by August 2019; the WHO estimated that the case fatality rate was 0.9%. In Hong Kong in May 2020, there were at least 10 cases of hepatitis E that were transmitted by rats, and possibly hundreds of cases that had a transmission mechanism that is not fully understood.


Evolution

The strains of HEV that exist today may have arisen from a shared ancestor virus 536 to 1344 years ago. Another analysis has dated the origin of Hepatitis E to ~6000 years ago, with a suggestion that this was associated with domestication of pigs. At some point, two
clades A clade (), also known as a monophyletic group or natural group, is a group of organisms that are monophyletic – that is, composed of a common ancestor and all its lineal descendants – on a phylogenetic tree. Rather than the English term, t ...
may have diverged — an anthropotropic form and an enzootic form — which subsequently evolved into genotypes 1 and 2 and genotypes 3 and 4, respectively. Whereas genotype 2 remains less commonly detected than other genotypes, genetic evolutionary analyses suggest that genotypes 1, 3, and 4 have spread substantially during the past 100 years.


References

''This article incorporates public domain text from the CDC as cited''


Further reading

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External links

{{Authority control +E Rodent-carried diseases Animal viral diseases Zoonoses Vaccine-preventable diseases E