Hepatitis A is an infectious, vaccine-preventable liver disease caused by Hepatitis A virus (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between exposure and symptoms, in those who develop them, is two to six weeks. When symptoms occur, they typically last eight weeks and may include nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain. Around 10–15% of people experience a recurrence of symptoms during the six months after the initial infection. Acute liver failure may rarely occur, with this being more common in the elderly. It is typically a foodborne illness, usually spread by eating food or drinking water contaminated with infected feces. Undercooked or raw shellfish are relatively common sources. It may also be spread through close contact with an infectious person. While children often do not have symptoms when infected, they are still able to infect others. After a single infection, a person is immune for the rest of their life. Diagnosis requires blood testing, as the symptoms are similar to those of a number of other diseases. It is one of five known hepatitis viruses: A, B, C, D, and E. The hepatitis A vaccine is effective for prevention. Some countries recommend it routinely for children and those at higher risk who have not previously been vaccinated. It appears to be effective for life. Other preventive measures include hand washing and properly cooking food. No specific treatment is available, with rest and medications for nausea or diarrhea recommended on an as-needed basis. Infections usually resolve completely and without ongoing liver disease. Treatment of acute liver failure, if it occurs, is with liver transplantation. Globally, around 1.4 million symptomatic cases occur each year and about 114 million infections (symptomatic and asymptomatic). It is more common in regions of the world with poor sanitation and not enough safe water. In the developing world, about 90% of children have been infected by age 10, thus are immune by adulthood. It often occurs in outbreaks in moderately developed countries where children are not exposed when young and vaccination is not widespread. Acute hepatitis A resulted in 11,200 deaths in 2015. World Hepatitis Day occurs each year on July 28 to bring awareness to viral hepatitis.
Signs and symptoms Early symptoms of hepatitis A infection can be mistaken for influenza, but some people, especially children, exhibit no symptoms at all. Symptoms typically appear two–six weeks (the incubation period) after the initial infection. About 90% of children do not have symptoms. The time between infection and symptoms, in those who develop them, is two–six weeks, with an average of 28 days. 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. Symptoms usually last less than 2 months, although some people can be ill for as long as 6 months:
Fatigue Fever Nausea Appetite loss Jaundice, a yellowing of the skin or the whites of the eyes owing to hyperbilirubinemia Bile is removed from the bloodstream and excreted in the urine, giving it a dark amber color Diarrhea Light or clay-colored faeces (acholic faeces) Abdominal discomfort
Extrahepatic manifestations Joint pains, red cell aplasia, pancreatitis and generalized lymphadenopathy are the possible extrahepatic manifestations. Kidney failure and pericarditis are very uncommon. If they occur, they show an acute onset and disappear upon resolution of the disease.
Virology
Taxonomy Hepatitis A virus is a species of virus in the order Picornavirales, family Picornaviridae, genus Hepatovirus. Humans and other vertebrates serve as natural hosts of this genus. Nine members of Hepatovirus are recognized. These species infect bats, rodents, hedgehogs, and shrews. Phylogenetic analysis suggests a rodent origin for human Hepatitis A. A member virus of hepatovirus B (Phopivirus) has been isolated from a seal. This virus shared a common ancestor with Hepatovirus A about 1800 years ago. Another hepatovirus – Marmota himalayana hepatovirus – has been isolated from the woodchuck Marmota himalayana. This virus appears to have had a common ancestor with the primate-infecting species around 1000 years ago.
Genotypes One serotype and six different genotypes (three human and three simian) have been described. 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 but has been reclassified as subgenotype IIB. Genotype III has been isolated from both humans and owl monkeys. Most human isolates are of genotype I. Of genotype I isolates, subtype IA accounts for the majority. The mutation rate in the genome has been estimated to be 1.73–9.76 × 10−4 nucleotide substitutions per site per year. The human strains appear to have diverged from the simian about 3600 years ago. The mean age of genotypes III and IIIA strains has been estimated to be 592 and 202 years, respectively.
Structure Hepatitis A virus is a picornavirus; it is not enveloped and contains a positive-sense, single-strand of RNA packaged in a protein shell. Only one serotype of the virus has been found, but multiple genotypes exist. Codon use within the genome is biased and unusually distinct from its host. It also has a poor internal ribosome entry site. In the region that codes for the HAV capsid, highly conserved clusters of rare codons restrict antigenic variability.
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