Blue Circle
Medi Services
Hepatitis A (formerly known as infectious hepatitis) is an acute infectious disease of the livercaused by the hepatitis A virus (HAV).[1] Many cases have few or no symptoms, especially in the young.[2] The time between infection and symptoms, in those who develop them, is between two and six weeks.[3] When symptoms occur, they typically last eight weeks and may include nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain.[2] Around 10–15% of people experience a recurrence of symptoms during the six months after the initial infection.[2] Acute liver failure may rarely occur with this being more common in the elderly.[2]
It is usually spread by eating or drinking food or water contaminated with infected feces.[2]Shellfish which have not been sufficiently cooked are a relatively common source.[4] It may also be spread through close contact with an infectious person.[2] While children often do not have symptoms when infected, they are still able to infect others.[2] After a single infection, a person is immune for the rest of his or her life.[5] Diagnosis requires blood testing, as the symptoms are similar to those of a number of other diseases.[2] It is one of five known hepatitis viruses: A,B, C, D, and E.
The hepatitis A vaccine is effective for prevention.[2][6] Some countries recommend it routinely for children and those at higher risk who have not previously been vaccinated.[2][7] It appears to be effective for life.[2] Other preventive measures include hand washing and properly cooking food.[2] No specific treatment is available, with rest and medications for nausea or diarrhearecommended on an as-needed basis.[2] Infections usually resolve completely and without ongoing liver disease.[2] Treatment of acute liver failure, if it occurs, is with liver transplantation.[2]
Globally, around 1.5 million symptomatic cases occur each year[2] and there were about 102 million cases in 2013.[8] It is more common in regions of the world with poor sanitation and not enough safe water.[7] In the developing world, about 90% of children have been infected by age 10, thus are immune by adulthood.[7] It often occurs in outbreaks in moderately developed countries where children are not exposed when young and vaccination is not widespread.[7] In 2010, acute hepatitis A resulted in 102,000 deaths.[9] World Hepatitis Day occurs each year on July 28 to bring awareness to viral hepatitis.[7]
Early symptoms of hepatitis A infection can be mistaken for influenza, but some sufferers, especially children, exhibit no symptoms at all. Symptoms typically appear 2 to 6 weeks (the incubation period) after the initial infection.[10] 90% of children do not have symptoms. The time between infection and symptoms, in those who develop them, is between two and six weeks with an average of 28 days.[3]
The risk for symptomatic infection is directly related to age, with more than 80% of adults having symptoms compatible with acute viral hepatitis and the majority of children having either asymptomatic or unrecognized infections.[11]
Symptoms usually last less than 2 months, although some people can be ill for as long as 6 months:[12]
| Hepatitis A | |
|---|---|
 | |
| Electron micrograph of hepatitis A virions | |
| Virus classification | |
| Group: | Group IV ((+)ssRNA) |
| Order: | Picornavirales |
| Family: | Picornaviridae |
| Genus: | Hepatovirus |
| Species: | Hepatovirus A |
| Synonyms | |
| |
Hepatovirus A is a species of virus in the order Picornavirales in the family Picornaviridae and is the type species of the genus Hepatovirus. Human and vertebrates serve as natural hosts.[14][15]
At least 13 additional species of the genus Hepatovirus have now been identified.[16] These species infectbats, rodents, hedgehogs and shrews. Phylogenetic analysis suggests a rodent origin for Hepatitis A.
A species of hepatovirus (Phopivirus) has been isolated from a seal.[17] This species shared a common ancestor with hepatitis A virus about 1800 years ago.
Another hepatovirus - Marmota Himalayana hepatovirus - has been isolated from the woodchuck Marmota himalayana.[18] This species appears to have had a common ancestor with the primate species ~1000 years ago.
One serotype and seven different genetic groups (four humans and three simian) have been described.[19]The human genotypes are numbered I-III. Six subtypes have been described (IA, IB, IIA, IIB, IIIA, IIIB). The simian genotypes have been numbered IV-VI. A single isolate of genotype VII isolated from a human has also been described.[20] Genotype III has been isolated from both humans and owl monkeys. Most human isolates are of genotype I.[21] Of the type I isolates subtype IA accounts for the majority.
The mutation rate in the genome has been estimated to be 1.73–9.76 x 10?4 nucleotide substitution per site per year.[22][23] The human strains appear to have diverged from the simian about 3600 years ago.[23]The mean age of genotypes III and IIIA strains has been estimated to be 592 and 202 years, respectively.[23]
Hepatovirus A is a picornavirus; it is nonenveloped and contains a single-stranded RNA packaged in a protein shell.[19] There is only oneserotype of the virus, but multiple genotypes exist.[24] Codon use within the genome is biased and unusually distinct from its host. It also has a poor internal ribosome entry site.[25] In the region that codes for the HAV capsid, highly conserved clusters of rare codons restrict antigenic variability.[14][26]
| Genus | Structure | Symmetry | Capsid | Genomic arrangement | Genomic segmentation |
|---|---|---|---|---|---|
| Hepatovirus | Icosahedral | Pseudo T=3 | Nonenveloped | Linear | Monopartite |
Humans and vertebrates serve as the natural hosts. Transmission routes are fecal-oral and blood.[14]
Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine.[27] The blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver macrophages). Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the virus to host receptors, which mediates endocytosis. Replication follows the positive-stranded RNA virus replication model. Positive-stranded RNA virus transcription is the method of transcription. Translation takes place by viral initiation. The virus exits the host cell by lysis, and viroporins. Virions are secreted into the bile and released in stool. HAV is excreted in large quantities about 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood. The incubation period is 15–50 days and mortality is less than 0.5%.
Within the liver hepatocytes, the RNA genome is released from the protein coat and is translated by the cell's own ribosomes. Unlike otherpicornaviruses, this virus requires an intact eukaryote initiating factor 4G (eIF4G) for the initiation of translation.[28] The requirement for this factor results in an inability to shut down host protein synthesis, unlike other picornaviruses. The virus must then inefficiently compete for the cellular translational machinery which may explain its poor growth in cell culture. Presumably for this reason, the virus has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. Precisely how this strategy works is not quite clear yet.
No apparent virus-mediated cytotoxicity occurs, presumably because of the virus' own requirement for an intact eIF4G and liver pathology is likely immune-mediated.
| Genus | Host details | Tissue tropism | Entry details | Release details | Replication site | Assembly site | Transmission |
|---|---|---|---|---|---|---|---|
| Hepatovirus | Humans; vertebrates | Liver | Cell receptor endocytosis | Lysis | Cytoplasm | Cytoplasm | Oral-fecal; blood |
The virus spreads by the fecal–oral route, and infections often occur in conditions of poor sanitation and overcrowding. Hepatitis A can be transmitted by the parenteral route, but very rarely by blood and blood products. Food-borne outbreaks are not uncommon,[29] and ingestion of shellfish cultivated in polluted water is associated with a high risk of infection.[30] About 40% of all acute viral hepatitis is caused by HAV.[27] Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection. The virus is resistant todetergent, acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60 °C. It can survive for months in fresh and salt water. Common-source (e.g., water, restaurant) outbreaks are typical. Infection is common in children in developing countries, reaching 100% incidence, but following infection, lifelong immunity results. HAV can be inactivated by chlorine treatment (drinking water), formalin(0.35%, 37 °C, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone (0.25%, 1 hour), and UV radiation (2 ?W/cm2/min).
In developing countries, and in regions with poor hygiene standards, the rates of infection with this virus are high[31] and the illness is usually contracted in early childhood. As incomes rise and access to clean water increases, the incidence of HAV decreases.[32] In developed countries, though, the infection is contracted primarily by susceptible young adults, most of whom are infected with the virus during trips to countries with a high incidence of the disease[3] or through contact with infectious persons.
Although HAV is excreted in the feces towards the end of the incubation period, specific diagnosis is made by the detection of HAV-specific IgM antibodies in the blood.[33] IgM antibody is only present in the blood following an acute hepatitis A infection. It is detectable from one to two weeks after the initial infection and persists for up to 14 weeks. The presence of IgG antibodies in the blood means the acute stage of the illness is past and the person is immune to further infection. IgG antibodies to HAV are also found in the blood following vaccination, and tests for immunity to the virus are based on the detection of this antibody.[33]
During the acute stage of the infection, the liver enzyme alanine transferase (ALT) is present in the blood at levels much higher than is normal. The enzyme comes from the liver cells damaged by the virus.[34]
Hepatovirus A is present in the blood (viremia) and feces of infected people up to two weeks before clinical illness develops.[34]
