Hepatitis A is an acute
infectious diseaseInfectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
of the
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
caused by the hepatitis A virus (Hep A), an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person. Tens of millions of individuals worldwide are estimated to
become infected with Hep A each year. The time between infection and the appearance of the symptoms (the
incubation periodIncubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
) is between two and six weeks and the average incubation period is 28 days.
In
developing countriesA developing country, also known as a less-developed country, is a nation with a low level of material well-being. Since no single definition of the term developing country is recognized internationally, the levels of development may vary widely within so-called developing countries...
, and in regions with poor hygiene standards, the
incidenceIncidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of infection with this virus is high and the illness is usually contracted in early childhood. As incomes rise and access to clean water increases, the incidence of HAV decreases. Hepatitis A infection causes no clinical signs and symptoms in over 90% of infected children and since the infection confers lifelong immunity, the disease is of no special significance to those infected early in life. In Europe, the United States and other industrialized countries, on the other hand, 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 or through contact with infectious persons.
HAV infection produces a self-limited disease that does not result in chronic infection or chronic liver disease. However, 10%–15% of patients might experience a relapse of symptoms during the 6 months after acute illness. Acute liver failure from Hepatitis A is rare (overall case-fatality rate: 0.5%). The risk for symptomatic infection is directly related to age, with >80% of adults having symptoms compatible with acute viral hepatitis and the majority of children having either asymptomatic or unrecognized infection. Antibody produced in response to HAV infection persists for life and confers protection against reinfection. The disease can be prevented by
vaccinationVaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
, and
hepatitis A vaccineHepatitis A vaccine is a vaccine against the hepatitis A virus. The first successful vaccine against it was invented by Maurice Hilleman at Merck. The vaccine protects against the virus in more than 95% of cases and provides protection from the virus for at least ten years...
has been proven effective in controlling outbreaks worldwide.
Signs and symptoms
Early symptoms of hepatitis A infection can be mistaken for
influenzaInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, but some sufferers, especially children, exhibit no symptoms at all. Symptoms typically appear 2 to 6 weeks, (the
incubation periodIncubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
), after the initial infection.
Symptoms usually last less than 2 months, although some people can be ill for as long as 6 months.:
- Fatigue
- Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
- Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
- Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
- Appetite loss
- Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, a yellowing of the skin or whites of the eyes
- Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
is removed from blood stream and excreted in urine, giving it a dark amber colour
- Clay-coloured feces
Virology
Following ingestion, HAV enters the bloodstream through the epithelium of the
oropharynxThe Oropharynx reaches from the Uvula to the level of the hyoid bone.It opens anteriorly, through the isthmus faucium, into the mouth, while in its lateral wall, between the two palatine arches, is the palatine tonsil....
or intestine. The blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver macrophages). Virions 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
IgMIGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
antibodies in the blood. The
incubation periodIncubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
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 members of the Picornaviruses this virus requires an intact eukaryote initiating factor 4G (eIF4G) for the initiation of translation. 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.
There is no apparent virus-mediated
cytotoxicityCytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
presumably because of the virus' own requirement for an intact eIF4G and liver pathology is likely immune-mediated.
Structure
The Hepatitis
virusA virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
(HAV) is a
PicornavirusA picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...
; it is
non-envelopedMany viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
and contains a single-stranded RNA packaged in a protein
shellA capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
.
There is only one serotype of the virus, but multiple genotypes exist.
Codon use within the genome is biased and unusually distinct from its host. It also has a poor
internal ribosome entry siteAn internal ribosome entry site, abbreviated IRES, is a nucleotide sequence that allows for translation initiation in the middle of a messenger RNA sequence as part of the greater process of protein synthesis...
In the region that codes for the HAV
capsidA capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
there are highly conserved clusters of rare codons that restrict antigenic variability.
Transmission
The virus spreads by the
fecal-oral routeThe fecal-oral route, or alternatively, the oral-fecal route or orofecal route is a route of transmission of diseases, in which they are passed when pathogens in fecal particles from one host are introduced into the oral cavity of another potential host.There are usually intermediate steps,...
and infections often occur in conditions of poor sanitation and overcrowding. Hepatitis A can be transmitted by the
parenteralParenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
route but very rarely by blood and blood products. Food-borne outbreaks are not uncommon, and ingestion of
shellfishShellfish is a culinary and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater environments, some kinds are found only in freshwater...
cultivated in polluted water is associated with a high risk of infection.
Approximately 40% of all acute viral hepatitis is caused by HAV. Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection. The virus is resistant to
detergentA detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...
, acid (pH 1), solvents (e.g.,
etherEthers are a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R'. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
,
chloroformChloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
), drying, and temperatures up to 60
oC. 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%
incidenceIncidence may refer to:* Incidence , a measure of the risk of developing some new condition within a specified period of time* Incidence , the binary relations describing how subsets meet...
, but following infection there is life-long
immunityImmunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
. HAV can be inactivated by:
chlorineChlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
treatment (drinking water), formalin (0.35%, 37
oC, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone (0.25%, 1 hour), and UV radiation (2 μW/cm
2/min).
Diagnosis
Although HAV is excreted in the feces towards the end of the
incubation periodIncubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
, specific diagnosis is made by the detection of HAV-specific
IgMIGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
antibodiesAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
in the blood. IgM antibody is only present in the blood following an
acuteAcute may refer to:* Acute accent* Acute angle* Acute * Acute * Acute toxicity...
hepatitis A infection. It is detectable from one to two weeks after the initial infection and persists for up to 14 weeks. The presence of IgG antibody in the blood means that the acute stage of the illness is past and the person is immune to further infection. IgG antibody to HAV is also found in the blood following
vaccinationVaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
and tests for immunity to the virus are based on the detection of this antibody.
During the acute stage of the infection, the liver enzyme alanine transferase (ALT) is present in the blood at levels much higher than is normal. The
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
comes from the liver cells that have been damaged by the virus.
Hepatitis A virus is present in the blood, (
viremiaViremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream.- Primary versus Secondary :...
), and feces of infected people up to two weeks before clinical illness develops.
Prevention
Hepatitis A can be prevented by
vaccinationHepatitis A vaccine is a vaccine against the hepatitis A virus. The first successful vaccine against it was invented by Maurice Hilleman at Merck. The vaccine protects against the virus in more than 95% of cases and provides protection from the virus for at least ten years...
, good
hygieneHygiene refers to the set of practices perceived by a community to be associated with the preservation of health and healthy living. While in modern medical sciences there is a set of standards of hygiene recommended for different situations, what is considered hygienic or not can vary between...
and
sanitationSanitation is the hygienic means of promoting health through prevention of human contact with the hazards of wastes. Hazards can be either physical, microbiological, biological or chemical agents of disease. Wastes that can cause health problems are human and animal feces, solid wastes, domestic...
.
The vaccine protects against HAV in more than 95% of cases for longer than 20 years. It contains inactivated hepatitis A virus providing active immunity against a future infection. The vaccine was first phased in 1996 for children in high-risk areas, and in 1999 it was spread to areas with elevating levels of infection.
The vaccine is given by injection. An initial dose provides protection starting two to four weeks after vaccination; the second booster dose, given six to twelve months later, provides protection for over twenty years.
Treatment
There is no specific treatment for hepatitis A. Sufferers are advised to rest, avoid fatty foods and alcohol (these may be poorly tolerated for some additional months during the recovery phase and cause minor relapses), eat a well-balanced diet, and stay hydrated.
Prognosis
The
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
Centers for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) in 1991 reported a low
mortality rateMortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
for hepatitis A of 4 deaths per 1000 cases for the general
populationA population is all the organisms that both belong to the same group or species and live in the same geographical area. The area that is used to define a sexual population is such that inter-breeding is possible between any pair within the area and more probable than cross-breeding with individuals...
but a higher rate of 17.5 per 1000 in those aged 50 and over. The risk of death from acute liver failure following HAV infection increases with age and when the person has underlying chronic liver disease.
Young children who are infected with hepatitis A typically have a milder form of the disease, usually lasting from 1–3 weeks, whereas adults tend to experience a much more severe form of the disease.
Epidemiology
Antibodies to HAV (anti-HAV) in the blood are a marker of past or current infection. High-income regions (Western Europe, Australia, New Zealand, Canada, the United States, Japan, the Republic of Korea, and Singapore) have very low HAV endemicity levels and a high proportion of susceptible adults, low-income regions (sub-Saharan Africa and parts of South Asia) have high endemicity levels and almost no susceptible adolescents and adults, and most middle-income regions have a mix of intermediate and low endemicity levels. Anti-HAV prevalence suggest that middle-income regions in Asia, Latin America, Eastern Europe, and the Middle East currently have an intermediate or low level of endemicity. The countries in these regions may have an increasing burden of disease from hepatitis A.
There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997. The agency estimates that there were as many as 270,000 cases each year from 1980 through 2000.
Cases
The most widespread hepatitis A outbreak in the 2003 United States hepatitis outbreak afflicted at least 640 people (killing four) in north-eastern
OhioOhio is a Midwestern state in the United States. The 34th largest state by area in the U.S.,it is the 7th‑most populous with over 11.5 million residents, containing several major American cities and seven metropolitan areas with populations of 500,000 or more.The state's capital is Columbus...
and south-western
PennsylvaniaThe Commonwealth of Pennsylvania is a U.S. state that is located in the Northeastern and Mid-Atlantic regions of the United States. The state borders Delaware and Maryland to the south, West Virginia to the southwest, Ohio to the west, New York and Ontario, Canada, to the north, and New Jersey to...
in late 2003. The outbreak was blamed on tainted
green onionScallions , are the edible plants of various Allium species, all of which are "onion-like", having hollow green leaves and lacking a fully developed root bulb.-Etymology:The words...
s at a restaurant in
Monaca, PennsylvaniaMonaca is a borough in Beaver County, Pennsylvania, United States along the Ohio River, northwest of Pittsburgh. Monaca was first incorporated as Phillipsburg in 1840, and had been known by that name since the 1820s. In 1892, the name of the borough was changed to Monaca in honor of the Native...
. In 1988, 300,000 people in Shanghai, China were infected with HAV after eating
clamsThe word "clam" can be applied to freshwater mussels, and other freshwater bivalves, as well as marine bivalves.In the United States, "clam" can be used in several different ways: one, as a general term covering all bivalve molluscs...
from a contaminated river.
See also
- Hepatitis B
- Hepatitis B in China
Hepatitis B is endemic in China. Of the 350 million individuals worldwide infected with the hepatitis B virus , one-third reside in China. As of 2006 China has immunized 11.1 million children in its poorest provinces as part of several programs initiated by the Chinese government and as part of the...
- Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
- Hepatitis D
Hepatitis D, also referred to as hepatitis D virus and classified as Hepatitis delta virus, is a disease caused by a small circular enveloped RNA virus. It is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a subviral satellite because it can propagate only in the...
- Hepatitis E
Hepatitis E is a viral hepatitis caused by infection with a virus called hepatitis E virus . HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kilobase genome. HEV has a fecal-oral transmission route. It is one of five known hepatitis viruses: A, B, C, D, and E...
- Hepatitis F
Hepatitis F is a hypothetical virus linked to hepatitis. Several hepatitis F candidates emerged in the 1990s; none of these reports have been substantiated....
- Hepatitis G
- Maurice Hilleman
Maurice Ralph Hilleman was an American microbiologist who specialized in vaccinology and developed over three dozen vaccines, more than any other scientist...
External links