Hepatitis A is a liver
infection caused by the hepatitis A virus (HAV).
HAV was first identified in 1973 as an
icosahedral, non-enveloped virus with a diameter
between 27 nm (nanometres) and 32 nm (Figure 1). The virus is a member of
the genus Hepatovirus and belongs to
the Picornavirus clade. The pathogen is made up of two components, namely, viral
protein and highly conserved, single-stranded, positive-sense
RNA, and is structurally one of the smallest and
simplest RNA viruses found in animals, making it
difficult to distinguish its icosahedral
geometry from other Picornaviruses. HAV is
transmitted primarily through the ingestion of water
and food, and food contaminated by
human feces, and reaches the liver - its targeted organ - through the bloodstream. HAV infection is
endemic in third world countries, and is prevalent in the Far East.
Figure 1. An electron
micrograph of hepatitis A virus.
Following ingestion, HAV enters the
bloodstream through the epithelium of the
intestine. The blood carries the virus to the
liver, and multiplies within hepatocytes and
Kupffer cells (liver macrophages). Virions
(empty capsids) are secreted into the bile and
released in stool. HAV is excreted in large
quantities approximately 11 days prior to
appearance of symptoms or anti-HAV
immunoglobulin M (IgM) antibodies in the blood.
Each capsid is made-up of 60 copies of viral
protein-1, viral protein-2, and viral protein-3.
Viral protein-1 and viral protein-3 are exposed
on the surface of the capsid, giving the virus
its conformational immunodominant antigenic
Within liver hepatocytes, the
RNA genome is released from the protein coat and
is translated by the host cell's own
protein-producing machinery, in particular, the
ribosomes. Unlike other Picornavirus members,
HAV requires an intact eukaryote
4G (eIF4G) for the initiation of translation.
The requirement for this factor results in an
inability to shut down host protein synthesis.
The virus must then inefficiently compete for
the cellular translational machinery, which may
explain why it requires a long adaptation period
to grow in cell culture. On the contrary,
members of the same family usually do not
require a long adaptation period to propagate in
The spread of HAV usually occurs in
epidemics and outbreaks, and thus nearly one in
three persons in the US have been tested
positive for antibodies against HAV. HAV is particularly unaffected
by environmental factors and can therefore
persist in the environment for a relatively long
period of time. In fact, the virus can survive
up to a month at room temperature. In order to inactivate HAV,
the virus must either be heated to temperatures greater
than 85°C, placed in ultraviolet radiation,
exposed to foramalin, iodine, or concentrated
chlorine. This is why it is crucial to steam and
cook shellfish collected from places that are
known to contain high levels of HAV, such as in Central America. Moreover, since
HAV is found in the stools of those infected
with the virus, improper washing of the hands
may lead to the spread of the virus. Those most at risk are
people in developing countries, where the
standards for hygiene and sanitation are very
Hepatitis A occurs only in
humans, but has been shown to infect test
organisms in vitro (Berkham & Bakalar, 2000).
The main target of HAV is the liver. This is
because the virus has surface antigens specific
for receptors found on liver cells only.
Generally, the liver
is responsible for purifying blood and
processing nutrients. A healthy liver is
essential to the functioning of blood,
lymph, and bile production. If the
liver fails, all other organs in the body will
soon start to fail. Unlike
and C viruses, HAV only causes an
acute infection, rather than chronic. In acute
infections, the liver recovers fully in most
people without any lingering after effects;
chronic infections are life long. Once an
individual has been infected with HAV and has
cleared the pathogen, the host develops
lifelong immunity to repeated infections.
In some rare cases, fulminant hepatitis
(acute liver failure)
develops; this can be fatal in people who are immunocompromised
(people with AIDS, leukemia, or cancer), have a
pre-existing hepatitis infection (hepatitis B or C), or those who are over the age of
40. The overall risk for death
is 0.3% for those persons under the age
of 40, while the
risk increases to 1.8% for those over 40 years
of age (Berkham & Bakalar, 2000).
Symptoms: The effects of HAV
infection range from
no symptoms to possible life-threatening
conditions in some rare cases. In
children less than the age of six, 70% of
infections are nonsymptamatic and if symptoms do
occur, it is usually
anicteric (Koopmans et al., 2008). Symptoms in older people include
fever, appetite lost, nausea, stomachache, darkened
urine, and jaundice (Figure 2).
Jaundice is characterized by the yellowish
staining of the skin or eyes. Jaundice is caused
by an increase in blood plasma bilirubin,
which is a chemical derivative of biliverdin - a chemical
breakdown component of hemoglobin.
Bilirubin is naturally yellow in colour, whereas biliverdin
is naturally green
(bilverdin is also the reason why bruised
yellowish-green after the onset of injury). Increased levels of bilirubin in the
blood suggests that red blood cells have been damaged and
have released free hemoglobin into the bloodstream. Usually
when the virus first enters the bloodstream, phagocytes such
as macrophages take up the virus and release potent chemical
agents, such as reactive oxygenated species and
nitric oxide, to destroy the pathogen. These chemicals have an
effect on neighboring cells, including red blood cells.
Since blood and lymph pass through the liver, kupffer cells
(specialized liver macrophages) and natural killer cells of
the immune system are actively destroying free-hepatitis A
virus flowing in the bloodstream and viral-infected cella,
respectively, and subsequently damaging red blood cells. Symptoms
typically last two months, but can extend up to six months in
roughly 10% of the population.
In 2000, there was an estimate 120000 new
cases of hepatitis A reported in the United
Figure 2. The
viral disease hepatitis A is manifested here as
icterus, or jaundice of the conjunctivae and
Diagnonis: The humoral immune response is very
important in diagnosing a person with HAV
infection. IgM, immunoglobulin A (IgA),
immunoglobulin G (IgG),
and anti-HAV antibodies make themselves present at the same
time the symptoms of the infection begin to
manifest themselves (Nainan et al.,
2006). Clinically, hepatitis caused by HAV is
not easy to differentiate from hepatitis caused
by other viruses, and therefore serologic
testing is needed to make an accurate diagnosis
(Nainan et al., 2006). The only way of detecting
whether a person is currently infected or was
previously infected is by conducting a blood
test for antibodies using capture enzyme-linked
immunosorbent assay (ELISA) (also known as
Although there is no cure for
hepatitis A, it can be prevented with a quick
and simple vaccine. Havrix, the vaccine
for hepatitis A, comes in two different
formulas, namely, one for children 2 to 18 years
of age and one for adults over the age of 18.
The two formulas differ in terms of dosage
amounts and dosage schedule. Vaccination takes
full affect four weeks after the first dose and
typically lasts 20 years.
Berkman, A. & Bakalar, N.
(2000). Hepatitis A to G. New York: Warner
Koopmans, M., Cliver, O.D., &
Bosh, A. (2008). Emerging issues in food safety:
Food bourne viruses Progress and Challenges.
United States: ASM Press.
Nainan, O.V., Xia, G.
Vaughan, G., & Margolis, H.S. (2006). Diagnosis
of Hepatitis A Virus Infection: a molecular
Approach. Clinical Microbiology, 19: