Hepatitis A

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Hepatitis A

Synonyms Infectious hepatitis

A case of jaundice caused by hepatitis A

Specialty Infectious disease, gastroenterology

Symptoms Nausea, vomiting, diarrhea, dark urine,

jaundice, fever, abdominal pain[1]

Complications Acute liver failure[1]

Usual onset 2–6 weeks after infection[2]

Duration 8 weeks[1]

Causes Eating food or drinking water

contaminated with hepatitis A virus
infected feces[1]
 Diagnostic method Blood tests[1]

Prevention Hepatitis A vaccine, hand washing,

properly cooking food[1][3]

Treatment Supportive care, liver transplantation[1]

Frequency 114 million symptomatic and

nonsymptomatic (2015)[4]

Deaths 11,200[5]

Hepatitis A is an infectious disease of the liver caused by the hepatitis A virus (HAV).[6] Many
cases have few or no symptoms, especially in the young.[1] The time between infection and
symptoms, in those who develop them, is between two and six weeks.[2] When symptoms occur,
they typically last eight weeks and may include nausea, vomiting, diarrhea, jaundice, fever, and
abdominal pain.[1] Around 10–15% of people experience a recurrence of symptoms during the six
months after the initial infection.[1] Acute liver failure may rarely occur, with this being more
common in the elderly.[1]

It is usually spread by eating food or drinking water contaminated with infected feces.[1] Shellfish
which have not been sufficiently cooked are a relatively common source.[7] It may also be spread
through close contact with an infectious person.[1] While children often do not have symptoms
when infected, they are still able to infect others.[1] After a single infection, a person is immune
for the rest of his or her life.[8] Diagnosis requires blood testing, as the symptoms are similar to
those of a number of other diseases.[1] It is one of five known hepatitis viruses: A, B, C, D, and E.

The hepatitis A vaccine is effective for prevention.[1][3] Some countries recommend it routinely for
children and those at higher risk who have not previously been vaccinated.[1][9] It appears to be
effective for life.[1] Other preventive measures include hand washing and properly cooking food.[1]
No specific treatment is available, with rest and medications for nausea or diarrhea
recommended on an as-needed basis.[1] Infections usually resolve completely and without
ongoing liver disease.[1] Treatment of acute liver failure, if it occurs, is with liver
transplantation.[1]

Globally, around 1.4 million symptomatic cases occur each year[1] and about 114 million
infections (symptomatic and asymptomatic).[4] It is more common in regions of the world with
poor sanitation and not enough safe water.[9] In the developing world, about 90% of children have
been infected by age 10, thus are immune by adulthood.[9] It often occurs in outbreaks in
moderately developed countries where children are not exposed when young and vaccination is
not widespread.[9] Acute hepatitis A resulted in 11,200 deaths in 2015.[5] World Hepatitis Day
occurs each year on July 28 to bring awareness to viral hepatitis.[9]

Contents
[hide]

 1Signs and symptoms

 2Virology
o 2.1Taxonomy
o 2.2Genotypes
o 2.3Structure
o 2.4Life cycle
o 2.5Transmission
 3Diagnosis
 4Prevention
o 4.1Vaccination
 5Treatment
 6Prognosis
 7Epidemiology
o 7.1Countries
 8References
 9External links

Signs and symptoms[edit]

Early symptoms of hepatitis A infection can be mistaken for influenza, but some sufferers,
especially children, exhibit no symptoms at all. Symptoms typically appear 2 to 6 weeks (the
incubation period) after the initial infection.[10] About 90% of children do not have symptoms.
The time between infection and symptoms, in those who develop them, is between 2 and 6 weeks
with an average of 28 days.[2]

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.[11]

Symptoms usually last less than 2 months, although some people can be ill for as long as 6
months:[12]

 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
colour
 Diarrhea
 Light, or clay-coloured faeces (acholic faeces)
 Abdominal discomfort[13]

Virology[edit]

Hepatitis A

Electron micrograph of hepatitis A

virions

Virus classification

Group: Group IV ((+)ssRNA)

Order: Picornavirales

Family: Picornaviridae

Genus: Hepatovirus

Species: Hepatovirus A

Synonyms
  Hepatitis A virus

Taxonomy[edit]

Hepatovirus A is a species of virus in the order Picornavirales in the family Picornaviridae and
is the type species of the genus Hepatovirus. Humans and vertebrates serve as natural hosts.[14][15]

At least 13 additional species of the genus Hepatovirus have now been identified.[16] These
species infect bats, rodents, hedgehogs, and shrews. Phylogenetic analysis suggests a rodent
origin for Hepatitis A.

A species of hepatovirus (Phopivirus) has been isolated from a seal.[17] This species shared a
common ancestor with hepatitis A virus about 1800 years ago.

Another hepatovirus - Marmota Himalayana hepatovirus - has been isolated from the
woodchuck Marmota himalayana.[18] This species appears to have had a common ancestor with
the primate-infecting species around 1000 years ago.

Genotypes[edit]

One serotype and seven different genetic groups (four human and three simian) have been
described.[19] 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.[20] Genotype III has been isolated
from both humans and owl monkeys. Most human isolates are of genotype I.[21] Of the type I
isolates subtype IA accounts for the majority.

The mutation rate in the genome has been estimated to be 1.73–9.76 x 10−4 nucleotide
substitutions per site per year.[22][23] The human strains appear to have diverged from the simian
about 3600 years ago.[23] The mean age of genotypes III and IIIA strains has been estimated to be
592 and 202 years, respectively.[23]

Structure[edit]

Hepatovirus A is a picornavirus; it is not enveloped and contains a single-stranded RNA

packaged in a protein shell.[19] Only one serotype of the virus has been found, but multiple
genotypes exist.[24] Codon use within the genome is biased and unusually distinct from its host. It
also has a poor internal ribosome entry site.[25] In the region that codes for the HAV capsid,
highly conserved clusters of rare codons restrict antigenic variability.[14][26]
 Genomic Genomic
Genus Structure Symmetry Capsid
arrangement segmentation
Pseudo
Hepatovirus Icosahedral Nonenveloped Linear Monopartite
T=3

Life cycle[edit]

Humans and vertebrates serve as the natural hosts. Transmission routes are fecal-oral and
blood.[14]

Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or
intestine.[27] The blood carries the virus to its target, the liver, where it multiplies within
hepatocytes and Kupffer cells (liver macrophages). Viral replication is cytoplasmic. Entry into
the host cell is achieved by attachment of the virus to host receptors, which mediates
endocytosis. Replication follows the positive-stranded RNA virus replication model. Positive-
stranded RNA virus transcription is the method of transcription. Translation takes place by viral
initiation. The virus exits the host cell by lysis and viroporins. Virions are secreted into the bile
and released in stool. HAV is excreted in large quantities about 11 days prior to the appearance
of symptoms or anti-HAV IgM antibodies in the blood. The incubation period is 15–50 days and
mortality is less than 0.5%.

Within the liver hepatocytes, the RNA genome is released from the protein coat and is translated
by the cell's own ribosomes. Unlike other picornaviruses, this virus requires an intact eukaryote
initiating factor 4G (eIF4G) for the initiation of translation.[28] The requirement for this factor
results in an inability to shut down host protein synthesis, unlike other picornaviruses. The virus
must then inefficiently compete for the cellular translational machinery which may explain its
poor growth in cell culture. Presumably for this reason, the virus has strategically adopted a
naturally highly deoptimized codon usage with respect to that of its cellular host. Precisely how
this strategy works is not quite clear yet.

No apparent virus-mediated cytotoxicity occurs, presumably because of the virus' own

requirement for an intact eIF4G, and liver pathology is likely immune-mediated.

Host Tissue Entry Release Replication Assembly

Genus Transmission
details tropism details details site site
Cell
Humans; Oral-fecal;
Hepatovirus Liver receptor Lysis Cytoplasm Cytoplasm
vertebrates blood
endocytosis

Transmission[edit]

The virus spreads by the fecal–oral route, and infections often occur in conditions of poor
sanitation and overcrowding. Hepatitis A can be transmitted by the parenteral route, but very
rarely by blood and blood products. Food-borne outbreaks are common,[29] and ingestion of
shellfish cultivated in polluted water is associated with a high risk of infection.[30] About 40% of
all acute viral hepatitis is caused by HAV.[27] Infected individuals are infectious prior to onset of
symptoms, roughly 10 days following infection. The virus is resistant to detergent, acid (pH 1),
solvents (e.g., ether, chloroform), drying, and temperatures up to 60°C. It can survive for months
in fresh and salt water. Common-source (e.g., water, restaurant) outbreaks are typical. Infection
is common in children in developing countries, reaching 100% incidence, but following
infection, lifelong immunity results. HAV can be inactivated by chlorine treatment (drinking
water), formalin (0.35%, 37°C, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone
(0.25%, 1 hour), and UV radiation (2 μW/cm2/min).

In developing countries, and in regions with poor hygiene standards, the rates of infection with
this virus are high[31] and the illness is usually contracted in early childhood. As incomes rise and
access to clean water increases, the incidence of HAV decreases.[32] In developed countries,
though, the infection is contracted primarily by susceptible young adults, most of whom are
infected with the virus during trips to countries with a high incidence of the disease[2] or through
contact with infectious persons.

Humans are the only natural reservoir of the virus. No known insect or other animal vectors can
transmit the virus. A chronic HAV state has not been reported.[33]