HAV is a single-stranded, positive-sense, linear RNA enterovirus of the Picornaviridae family.

In humans, viral
replication depends on hepatocyte uptake and synthesis, and assembly occurs exclusively in the liver cells.
Virus acquisition results almost exclusively from ingestion (eg, fecal-oral transmission), although isolated cases
of parenteral transmission have been reported.

HAV is an icosahedral nonenveloped virus, measuring approximately 28 nm in diameter (see the image below).
Its resilience is demonstrated by its resistance to denaturation by ether, acid (pH 3.0), drying, and temperatures
as high as 56C and as low as -20C. The hepatitis A virus can remain viable for many years. Boiling water is
an effective means of destroying it. Chlorine and iodine are similarly effective.

Various genotypes of HAV exist; however, there appears to be only 1 serotype. Virion proteins 1 and 3 are the
primary sites of antibody recognition and subsequent neutralization. No antibody cross-reactivity has been
identified with other viruses causing acute hepatitis. Evidence in recent years appears to show the exosomes
play a dual role in the transmission of HAV and HCV, allowing these viruses to evade antibody-mediated
immune responses but, paradoxically, can also be detected by plasmacytoid dendritic cells (pDCs) leading to
innate immune activation and type I interferon production.[1]

Liu et al performed phylogenetic and recombination analyses on 31 complete HAV genomes from infected
humans and simians. They identified 3 intra-genotypic recombination events (I-III), which they believe
demonstrate that humans can be co-infected with different HAV subgenotypes.[2]

The first recombination event (I) occurred between the lineage represented by the Japanese isolate AH2
(AB020565, subgenotype IA), and the second event (II) occurred between the lineage represented by the North
African isolate MBB (M20273, subgenotype IB).[2] These 2 recombination events resulted in the recombinant
Uruguayan isolate HAV5 (EU131373).

The third recombination event (III) occurred between the North African lineage (isolate MBB; M20273,
subgenotype IB) and the German lineage (isolate GBM; X75215, subgenotype IA), leading to the Italian isolate
FG (X83302).[2]

Hepatocyte uptake involves a receptor, identified by Kaplan et al, on the plasma membrane of the cell, and viral
replication is believed to occur exclusively in hepatocytes.[3] The demonstration of HAV in saliva has raised
questions about this exclusivity. After entry into the cell, viral RNA is uncoated, and the host ribosomes bind to
form polysomes. Viral proteins are synthesized, and the viral genome is copied by a viral RNA polymerase (see
the image below). Assembled virus particles are shed into the biliary tree and excreted in the feces.

Minimal cellular morphologic changes result from hepatocyte infection. The development of an immunologic
response to infection is accompanied by a predominantly portal and periportal lymphocytic infiltrate and a
varying degree of necrosis.

Many authorities believe that hepatocyte injury is secondary to the hosts immunologic response. This
hypothesis is supported by the lack of cytotoxic activity in tissue culture and correlations between immunologic
response and manifestations of hepatocyte injury.

Person-to-person contact is the most common means of transmission and is generally limited to close contacts.
Transmission through blood products has been described. The period of greatest shedding of HAV is during
the anicteric prodrome (14-21 d) of infection and corresponds to the time when transmission is highest (see the
image below). Recognizing that the active virus is shed after the development of jaundice is important, although
amounts fall rapidly.

Outbreaks of acute hepatitis A have received international attention. The most notable report of transmission
appeared in the New England Journal of Medicine.[4]This report describes a point source epidemic of HAV
infection at a Pennsylvania restaurant where the vehicle for transmission was green onions used to make a
mild salsa. The contamination of the onions occurred before the vegetable arrived in the United States.

The incubation period usually lasts 2-6 weeks, and the time to onset of symptoms may be dose related. The
presence of disease manifestations and the severity of symptoms after HAV infection directly correlate with
patient age. In developing nations, the age of acquisition is before age 2 years. In Western societies,
acquisition is most frequent in persons aged 5-17 years. Within this age range, the illness is more often mild or
subclinical; however, severe disease, including fulminant hepatic failure, does occur.
The hepatitis A virus (HAV) is very stable, withstandingsubstantial heat, drying,low pH and
detergents. This means it is able to survive in the environment (including in foods and drinking
water) and acid barrier of the stomach, and be excreted in the bile, leading to faecal shedding. The
mechanisms responsible for hepatocellularinjury remain poorly characterised but appear to
be caused by the host s response to infection rather than a direct cytopathic effect of the virus.
The long incubation phase of the virus is related to its ability to interfere with normal mechanisms
for the recognition of viral infection and resultant synthesis of interferon (IFN) - . With the onset
of hepatocellular injury, HLA - restricted, virus specic,cytotoxic,CD8 T cells begin to secrete
IFN which stimulates the recruitment of additional,non -specic inammatory cells,causing
hepatocellular injury. The secretion of neutralising antibodies occurs concurrent with the earliest
evidence of serum aminotransferase elevation and hepatocellular injury. Neutralising antibody is of
primary importance in protection against HAV infection and disease.