Reports of illness resembling hepatitis A virus (HAV) infection were described in Greek writings from the fourth century BC.1 Once referred to as epidemic jaundice, catarrhal jaundice, and infectious hepatitis, hepatitis A outbreaks have been well documented since the eighteenth century.1 In 1973, hepatitis A viral particles were visualized for the first time using electron microscopy and were identified as the etiologic agent of hepatitis A.2,3 These findings led to the development of diagnostic tests that could differentiate acute from past HAV infection, the propagation of HAV in cell culture, and the development and licensure of hepatitis A vaccines. HAV spreads primarily by the fecal-oral route, either by direct contact with an infected individual or through consumption of contaminated food or water. In 2015, the World Health Organization estimated that 1.4 million hepatitis A cases occur globally each year.4
HAV is a 27 nm, spherical, nonenveloped virus with an icosahedral capsid configuration, and is a member of the Hepatovirus A species in the genus Hepatovirus and the family Picornaviridae.5,6 The HAV genome is composed of a single-stranded, positive sense RNA molecule whose organization and replication scheme are similar to poliovirus and other members of the family Picornaviridae. Unlike other picornaviruses, HAV does not commandeer the host replication machinery but coexists with the host by using codons rarely used by the host. HAV infects primates and replicates predominantly in the liver where it infects hepatocytes. HAV can also infect epithelial cells in the small intestine. The virus hijacks host cellular membranes to cloak itself from host immune response and is excreted as naked virions in feces and into the blood stream as enveloped virions.7
Antibody binding studies indicate there is only a single HAV serotype. HAV isolates from diverse geographic areas are recognized by polyclonal antibody generated against capsid proteins (anti-HAV) and by neutralizing monoclonal antibodies to human HAV. Although HAV has little phenotypic diversity, enough genetic diversity exists in the capsid region to define six genotypes and allow for studies of molecular relatedness.8 Genotypes I–III infect humans while genotypes IV–VI infect simians.
Compared to other picornaviruses, HAV is more resistant to inactivation by heating, to pH less than 3, to drying at ambient temperature, and to low concentrations of free chlorine or hypochlorite.9,10 HAV is also resistant to freezing and remains infectious in feces or on environmental surfaces for several weeks.11,12 HAV can be inactivated by many common disinfecting chemicals, including hypochlorite (bleach) and quaternary ammonium formulations containing 23% HCl, found in many toilet bowl cleaners.13 HAV is only partially inactivated by pasteurization (60°C for 1 hour) but is completely inactivated in food by heating to temperatures higher than 85°C (>185ºF) for at least 1 minute.13 HAV grows poorly in cell culture where it requires a very long adaptation period (up to 1 ...