HAV does not cause chronic infections, unlike other hepatitis viruses. Relapsing hepatitis occurs in about 3–20% of patients, usually 3 to 12 weeks after the initial episode, but the symptoms are less severe than the initial ones. Fulminant hepatitis is rare, occurring in less than 1% of cases, but cholestatic forms and relapsing hepatitis have also been described. Older patients are at increased risk of severe outcomes, hospitalization, and death. While infection is largely asymptomatic in children (>90% of children less than 6 years old), symptoms are much more common (>70%) in adults. The next, icteric, phase is defined by jaundice and hepatic cytolysis with elevated serum aminotransferase activities. The 4-week initial incubation period is often followed by a nonspecific prodromal phase during which a person suffering from infection can experience flu-like syndrome and intestinal disorders for a few days. There is only one serotype despite the existence of several genotypes. A third subgenotype, named IC, has been proposed for genotype I but is not yet recognized by the ICTV. Among them, only genotypes I, II, and III, further divided into subtypes A and B, infect humans. Based on the latest International Committee on Taxonomy of Viruses (ICTV) report, HAV is now classified into five genotypes. This polyprotein is processed by viral (protease 3C) and host cell proteases to give the structural (VP4, VP2, VP3, and VP1) and the non-structural mature proteins (2B, 2C, 3A, 3B, 3C (protease), and 3D (RNA-dependent RNA polymerase)). HAV has a single positive-strand 7.5 kb RNA genome with a single open reading frame (ORF) encoding one large polyprotein. Naked virions are quasi-enveloped virions in which the membrane has been removed by the detergent action of bile acids within the biliary canaliculus before they are excreted in the faeces. Quasi-enveloped virions have a lipid membrane and are found in the blood and culture supernatants. There are two types of infectious HAV particles: naked and quasi-enveloped virions. The hepatitis A virus (HAV) belongs to the Hepatovirus genus within the Picornaviridae family. The development of HAV antivirals may be important to control HAV outbreaks in developed countries where a universal vaccination programme is not recommended. Several countries have successfully introduced universal mass vaccination for children, but high-risk groups in high-income countries remain insufficiently protected. Hepatitis A infections can be prevented by vaccination safe and effective vaccines have been available for decades. Most of these outbreaks occur among high-risk groups: travellers, men who have sex with men, people who use substances, and people facing homelessness. The populations of developed countries are highly susceptible to HAV, and large outbreaks can occur when the virus is spread by globalization and by increased travel and movement of foodstuffs. Paradoxically, improving sanitary conditions in these countries, which reduces the incidence of HAV infections, can lead to more severe disease in susceptible adults. The virus is endemic in low-income countries where sanitary and sociodemographic conditions are poor. It is transmitted mainly by direct contact with patients who have been infected or by ingesting contaminated water or food. The hepatitis A virus (HAV) is a leading cause of acute viral hepatitis worldwide.
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