Hepatitis A; Causes, Symptoms, Diagnosis, Treatment

Hepatitis A








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Hepatitis A is an acute, necroinflammatory disease of the liver which results from infection by the hepatitis A virus (HAV). Hepatitis A virus is a positive-sense, single-stranded RNA virus classified within the genus Hepatovirus of the family Picornaviridae []. The chief mode of transmission for HAV is through the fecal-oral route, including person-to-person spread, and contaminated water or food products, but it has also been associated with outbreaks in injecting drug users and men who have sex with men [, ]. The virus is very resistant in the environment as well as to several preservation methods (acidification or freezing) [].

Hepatitis A is an acute infection of the liver caused by a small, non-enveloped hepatotropic virus classified in the genus Hepatovirus within the family Picornaviridae. Hepatitis A virus and HEV are acquired by consuming food and water contaminated by the virus (excreted in-patient’s stool) by way of the fecal-oral. HBV, HCV are contagious by blood and blood products, also may be transmitted by sexual contact. Vaccine for hepatitis A and B is available, but no vaccine is available for hepatitis C or E.

Hepatitis A is a vaccine-preventable, communicable disease of the liver caused by the hepatitis A virus (HAV). It is usually transmitted person-to-person through the fecal-oral route or consumption of contaminated food or water. Hepatitis A is a self-limited disease that does not result in chronic infection. Most adults with hepatitis A have symptoms, including fatigue, low appetite, stomach pain, nausea, and jaundice, which usually resolve within 2 months of infection; most children less than 6 years of age do not have symptoms or have an unrecognized infection. Antibodies produced in response to hepatitis A infection last for life and protect against reinfection. The best way to prevent hepatitis A infection is to get vaccinated.

Causes and Transmission of Hepatitis A

  • Transmission – Types of foods implicated in the transmission of HAV include shellfish, salads, sandwiches, vegetables, fruits, reconstituted frozen orange juice, ice cream, cheese, rice pudding, iced cake, custard, milk, bread, cookies and other raw or undercooked foods [. Contamination of foods with HAV can occur in several different ways: fruits and vegetables cultivated in and/or irrigated with fecally contaminated materials; shellfish are grown in and harvested from fecally polluted waters [; processing and preparation of food in fecally soiled equipment; and handling of ready-to-eat items of food by infected individuals with poor personal hygiene [.
  • Person-to-person transmission through the fecal-oral route – (i.e., ingestion of something that has been contaminated with the feces of an infected person) is the primary means of HAV transmission in the United States. Infections in the United States result primarily from travel to another country where hepatitis A virus transmission is common, close personal contact with infected persons, sex among men who have sex with men, and behaviors associated with injection drug use. [rx,rx]
  • Exposure to contaminated food or water – can cause common-source outbreaks and sporadic cases of HAV infection. Uncooked foods contaminated with HAV can be a source of outbreaks, as well as cooked foods that are not heated to temperatures capable of killing the virus during preparation (i.e., 185 degrees F [>85 degrees C] for one minute) and foods that are contaminated after cooking, as occurs in outbreaks associated with infected food handlers [rxrx]. Waterborne outbreaks are infrequent in developed countries with properly maintained sanitation and water supplies [rx]. In the United States, floods are unlikely to cause outbreaks of communicable diseases, and outbreaks of HAV caused by flooding have not been documented (see Floodwater After a Disaster or Emergency).
  • The virus most commonly spreads – when you eat or drink something contaminated with fecal matter, even just tiny amounts. It does not spread through sneezing or coughing. Here are some of the specific ways the hepatitis A virus can spread:
    • Eating food handled by someone with the virus who doesn’t thoroughly wash his or her hands after using the toilet
    • Drinking contaminated water
    • Eating raw shellfish from water polluted with sewage
    • Being in close contact with a person who’s infected — even if that person has no signs or symptoms
    • Having sex with someone who has the virus

Who is at increased risk for acquiring hepatitis A virus (HAV) infection?

  • Persons with direct contact with persons who have hepatitis A
  • Men who have sex with men
  • Users of injection and non-injection drugs
  • Persons with clotting factor disorders
  • Persons working with nonhuman primates
  • Household members and other close personal contacts of adopted children newly arriving from countries with high or intermediate hepatitis A endemicity

Who should be vaccinated against hepatitis A?

The Advisory Committee on Immunization Practices (ACIP) recommends that the following persons be vaccinated against hepatitis A:

  • All children at age 1 year,
  • People with unstable housing or experiencing homelessness
  • Persons who are at increased risk for infection,
  • Persons who are at increased risk for complications from hepatitis A, and
  • Any person wishing to obtain immunity (protection).

Children

  • ACIP recommends that all children in the United States receive hepatitis A vaccine at 1 year of age (i.e., 12-23 months) to avoid interference by passive maternal anti-HAV that may be present during the first year of life.
  • In the United States, children who are not vaccinated by 2 years of age can be vaccinated at subsequent visits; vaccination can be considered for children 2 to 18 years old and for anyone who wants protection against hepatitis A infection.  Booster doses are not recommended.

Persons at Increased Risk for Hepatitis A Infection

  • Persons traveling to or working in countries that have high or intermediate endemicity of hepatitis A – Persons who travel to developing countries are at high risk for hepatitis A, even those traveling to urban areas, staying in luxury hotels, and those who report maintaining good hand hygiene and being careful about what they drink and eat.
  • Men who have sex with men  Men who have sex with men should be vaccinated.
  • Users of injection and non-injection drugs Persons who use the injection and non-injection drugs should be vaccinated.
  • Persons who have an occupational risk for infection  Persons who work with HAV-infected primates or with HAV in a research laboratory setting should be vaccinated. No other groups have been shown to be at increased risk for HAV infection because of occupational exposure.
  • Persons who have chronic liver disease Persons with chronic liver disease who have never had hepatitis A should be vaccinated, as they have a higher likelihood of having fulminant hepatitis A (i.e., rapid onset of liver failure, often leading to death). Persons who are either awaiting or have received liver transplants also should be vaccinated.
  • Persons who have clotting-factor disorders  Persons who have never had hepatitis A and who are administered clotting-factor concentrates, especially solvent detergent-treated preparations, should be vaccinated.
  • Household members and other close personal contacts of adopted children newly arriving from countries with high or intermediate hepatitis A endemicity.  Previously unvaccinated persons who anticipate close personal contact (e.g., household contact or regular babysitting) with an international adoptee from a country of high or intermediate endemicity during the first 60 days following the arrival of the adoptee in the United States should be vaccinated. The first dose of the 2-dose hepatitis A vaccine series should be administered as soon as adoption is planned, ideally 2 or more weeks before the arrival of the adoptee.
  • Persons with direct contact with persons who have hepatitis A – Persons who have been recently exposed to HAV and who have not previously received hepatitis A vaccine should be vaccinated.

Symptoms of Hepatitis A

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.[rx] 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.[rx, rx] 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.[rx]

Initial symptoms

The initial symptoms of hepatitis A can include:

  • Feeling tired and generally unwell
  • Joint and muscle pain
  • A raised temperature
  • Loss of appetite
  • Feeling or being sick
  • Pain in the upper right part of your tummy
  • a headache, sore throat and cough
  • constipation or diarrhea
  • a raised, itchy rash (hives)

These symptoms usually last from a few days up to a couple of weeks.

Later symptoms

After the initial symptoms, the following symptoms may develop:

Most people make a full recovery within a couple of months, although the symptoms can come and go for up to 6 months.

Signs of a serious problem

Hepatitis A is not usually serious, but in rare cases, it can cause the liver to stop working properly (liver failure).

As well as the symptoms mentioned, signs of liver failure can include:

Get medical advice as soon as possible if you have these symptoms. Liver failure can be life-threatening if not treated quickly.

Symptoms Overall of hepatitis A include the following

  • Asymptomatic infection
  • Symptomatic infection with jaundice, dark urine, and clay-colored stool
  • Cholestatic hepatitis with prolonged alkaline phosphatase and bilirubin elevation and pruritus
  • Relapsing infection
  • Fulminant hepatitis.
  • A general feeling of being unwell (malaise)
  • Flu-like symptoms (e.g., headaches, muscle aches, low-grade fever)
  • Nausea and vomiting, abdominal pain
  • Jaundice (new or uncharacteristic yellow tinge to the skin and mucous membranes)
  • Diarrhea
  • Itching of the skin
  • Tea- or dark-colored urine
  • Pale bowel movements
  • 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 color
  • Diarrhea
  • Light, or clay-colored feces (acholic feces)
  • Abdominal discomfort[rx]

Extrahepatic manifestations

  • Joint pains, red cell aplasia, pancreatitis and generalized lymphadenopathy are the possible extrahepatic manifestations. Renal failure and pericarditis are very uncommon.[rx] If they occur, they show an acute onset and disappear upon resolution of the diseases


Diagnosis of Hepatitis A

Your doctor will suspect hepatitis if you have the symptoms above and you have high levels of liver enzymes when he tests your blood. He’ll confirm the diagnosis with these blood tests:

  • A test will be ordered to detect antibodies – to hepatitis A. The results of this test will also determine if the patient has been recently exposed to HAV.
  • Blood probably – will be tested for the hepatitis B and hepatitis C viruses, and others. For example, if a patient has had a large amount of vomiting or has not been able to take in liquids, the blood electrolytes may be out of balance. Blood chemistry may be tested to check electrolytes.
  • IgM (immunoglobulin M) antibodies – Your body makes these when you’re first exposed to hepatitis A. They stay in your bloodstream for about 3 to 6 months.
  • IgG ( immunoglobulin G) antibodies – These show up after the virus has been in your body for a while. You may have them all your life. They protect you against hepatitis A for the rest of your life. If you test positive for them but not for IgM antibodies, it means you had a hepatitis A infection in the past or you’ve been vaccinated against it.

Treatment of Hepatitis A

  • Get plenty of rest – especially during the initial stages of the infection, as you’ll probably feel very tired
  • Take painkillers – such as paracetamol or ibuprofen, if you have any aches and pains – how much you can take depends on how well your liver is working (ask your GP for advice)
  • Reduce itching by maintaining a cool –  well-ventilated environment, wearing loose clothing and avoiding hot baths or showers  your GP may recommend using an antihistamine in severe cases
  • Eat small light meals to help reduce nausea and vomiting – your GP can prescribe a medication called an antiemetic if the problem persists.
  • Get some rest – You’ll probably feel tired, sick, and have less energy than before you were infected.
  • Manage nausea – Nausea can make it difficult to eat. Try snacking throughout the day rather than eating full meals. To get enough calories, eat more high-calorie foods. For instance, drink fruit juice or milk rather than water. Drinking plenty of fluids is important to prevent dehydration if vomiting occurs.
  • Try to keep food down – Nausea that comes with hepatitis A can make it tough to eat. It may be easier to snack during the day than to eat full meals. To make sure you get enough, go for more high-calorie foods and drink fruit juice or milk instead of water. Fluids will also help keep you hydrated if you’re throwing up.
  • Avoid alcohol – It’s hard for your liver to process medications and alcohol. Plus, drinking can lead to added liver damage. Tell your doctor about any medications you take, including over-the-counter drugs.

Types of Hepatitis A Vaccine

There are 3 main types of hepatitis A vaccination:

  • a vaccine for hepatitis A only
  • a combined vaccine for hepatitis A and hepatitis B
  • a combined vaccine for hepatitis A and typhoid fever

Hepatitis A vaccination (minimum age: 12 months for routine vaccination)

Routine vaccination

  •  2-dose series (Havrix 6–12 months apart or Vaqta 6–18 months apart, minimum interval 6 months); a series began before the 2nd birthday should be completed even if the child turns 2 before the second dose is administered.

Catch-up vaccination

  • Anyone 2 years of age or older may receive the HepA vaccine if desired. The minimum interval between doses: 6 months
  • Adolescents 18 years and older may receive the combined HepA and HepB vaccine, Twinrix, as a 3-dose series (0, 1, and 6 months) or 4-dose series (0, 7, and 21–30 days, followed by a dose at 12 months).

International travel

  • Persons traveling to or working in countries with high or intermediate endemic hepatitis A:
    • Infants age 6–11 months: 1 dose before departure; revaccinate with 2 doses, separated by 6–18 months, between 12 to 23 months of age
    • Unvaccinated age 12 months and older: 1st dose as soon as travel considered

Commercial vaccines

Vaccines to prevent hepatitis A

VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ROUTE SCHEDULE BOOSTER
Hepatitis A vaccine, inactivated Havrix (GlaxoSmithKline) 1–18 0.5 mL (720 ELU) IM 0, 6–12 mo None
≥19 1.0 mL (1,440 ELU) IM 0, 6–12 mo None
Hepatitis A vaccine, inactivated Vaqta (Merck & Co., Inc.) 1–18 0.5 mL (25 U) IM 0, 6–18 mo None
≥19 1.0 mL (50 U) IM 0, 6–18 mo None
Combined hepatitis A and B vaccine Twinrix (GlaxoSmithKline ≥18 (primary) 1.0 mL (720 ELU HAV + 20 μg HBsAg) IM 0, 1, 6 mo None
≥18 (accelerated) same as above IM 0, 7, 21–30 d 12 mo

Abbreviations: ELU, ELISA units of inactivated HAV; IM, intramuscular; U, units HAV antigen; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen.

Several commercial hepatitis vaccines are available. The definition of (U)nits varies among manufacturers depending on how hepatitis A antigen is measured in their products.

  • Avaxim –  made by Sanofi Pasteur. Inactivated hepatitis A virus produced in MRC-5 cells. Each dose contains 160 U of antigen adsorbed on aluminum hydroxide (0.3 mg Al).[rx]
  • Epaxal – made by Crucell. Also sold under the brand names HAVpur and VIROHEP-A. This vaccine consists of virosomes, artificial particles composed of synthetic lipids and influenza proteins in addition to the hepatitis A antigen. It does not contain aluminium.[rx]
  • Havrix – made by GlaxoSmithKline. Inactivated hepatitis A virus produced in MRC-5 cells. Each adult dose contains 1440 ELISA units of viral antigen adsorbed on aluminum hydroxide (0.5 mg Al). The pediatric (child) doses contain half the amount of viral antigen and aluminum.[rx]
  • Healive – made by Sinovac. Inactivated hepatitis A virus cultured in human diploid cells, followed by harvest, purification, inactivation, and aluminum adsorption. Each adult dose contains 500 U of viral antigen. The pediatric dose contains 250 U of viral antigen.
  • Vaqta – made by Merck. Inactivated hepatitis A virus produced in MRC-5 cells. An adult dose contains 50 U of antigen adsorbed onto 0.45 mg of aluminum (as aluminum hydroxyphosphate sulfate); a child dose contains half the amounts of antigen and aluminum.[rx]
  • Biovac-A –  made by Pukang, sold under the brand name Biovac-A in India and under the brand name Mevac-A in Guatemala, Philippines, Bangladesh, Nepal, Uzbekistan, and Chile. It is a freeze-dried live attenuated hepatitis A vaccine. Hepatitis A virus H2 strain is produced in human diploid cells. A pack of 0.5ml vial of Biovac-A and 0.5ml ampoule of SWFI (sterile water for injection), contains not be less than 6.5 Lg CCID50. Only a single dose is needed. It is recommended by the WHO. Long term persistence research data predicated that sero-conversion remained and the antibody titer was not less than 128 IU/ml, 15 years after vaccination.

Combination vaccines

  • Hepatitis A and B vaccine is a vaccine against hepatitis A and hepatitis B.
  • Hepatitis A and typhoid vaccine is a vaccine against hepatitis A and typhoid.[rx][rx]

Hepatitis A virus vaccination recommendations by the British human immunodeficiency virus Association, the European AIDS Clinical Society, the US Advisory Committee for Immunization Practices and the World Health Organization

Health Authority Target candidates Dosing Schedule Comments
BHIVA[] Household and sexual contacts of infected persons Monovalent HAV vaccine recommended We support the BHIVA’s recommendations of targeted vaccination during outbreaks and of stratifying dosing schedule by CD4 counts, particularly administering a 3-dose schedule for those with lower CD4 counts. Despite waning antibody levels, we could not find evidence to justify routine boosters every 10 yr for those at risk. It may be preferable to follow antibody titers and revaccinate seroreverters
Travellers Patients with CD4 counts > 350 cells/mm3 should be offered 2 vaccine doses at 0 and 6 mo
MSM
Injecting and non-injecting drug users Patients with CD4 counts < 350 cells/mm3 should receive 3 vaccine doses at 0, 1, and 6 mo
Individuals at risk of infection during outbreaks
Those with occupational exposure to HAV (e.g., laboratory workers, sewage workers) Patients at continued risk of exposure receive a boosting vaccine dose every 10 yr
Hemophiliacs Following a significant exposure, HIV-positive contacts who are HAV-seronegative receive post-exposure prophylaxis with the HAV vaccine, with the first dose given as soon as possible and within 14 d of exposure; if the CD4 count is < 200 cells/mm3, they should also receive human normal immunoglobulin
Residents of care institutions, and their caregivers
EACS[] Travelers Vaccinate if seronegative. Did not specify how A shorter list of at-risk candidates for vaccination. Our review supports their recommendation to check antibody titers in individuals with risk profile to guide the need for primary or booster vaccinations
MSM
IDUs
Active hepatitis B or C infection
ACIP[] MSM Monovalent vaccine formulations should be administered in a 2-dose schedule at either 0 and 6-12 mo (Havrix), or 0 and 6-18 mo (Vaqta) Unlike BHIVA, in addition to the monovalent vaccine formulations, ACIP also recommends the combined hepatitis A and B vaccine
Injection or non-injection illicit drugs users
Persons working with HAV-infected primates or
with HAV in a research laboratory setting
Persons with chronic liver disease If the combined hepatitis A and hepatitis B vaccine (Twinrix) is used, administer 3 doses at 0, 1, and 6 mo; alternatively, a 4-dose schedule may be used, administered on days 0, 7, and 21-30 followed by a booster dose at 12 mo No mention of the need to follow antibody titers or booster vaccines or the application of immunization during outbreaks
Persons who receive clotting factor concentrates
Travellers
Close personal contact (e.g., household or regular babysitting) with an international adoptee during the first 60 d after arrival in the United States from a country with high or intermediate endemicity
WHO[] Travellers Inactivated vaccine: 2 doses, the second dose normally 6 mo after the first. If needed, this interval may be extended to 18-36 mo Does not specify whether all HIV-positive persons should be considered as immunosuppressed patients although evidence from Table ​[rx] suggests that except for the duration of viremia acute HAV is not more severe in HIV-positive compared to HIV-negative patients
Immunosuppressed patients
Patients with chronic liver disease

HAV: Hepatitis A virus; HIV: Human immunodeficiency virus; IDUs: Injecting drug users.

Precautions and Contraindications

  • Hepatitis A–containing vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component, including neomycin. Twinrix should not be administered to people with a history of hypersensitivity to yeast.
  • The tip caps of prefilled syringes of Havrix and Twinrix and the vial stopper, syringe plunger stopper, and tip caps of Vaqta may contain dry natural rubber, which may cause allergic reactions in latex-sensitive people. Because hepatitis A vaccine consists of inactivated virus, and hepatitis B vaccine consists of a recombinant protein, no special precautions are needed for vaccination of immunocompromised travelers. Providers should check precautions and contraindications before administering IG.

Pregnancy

  • Hepatitis A vaccine is considered safe for pregnant women. A recent review of the Vaccine Adverse Event Reporting System did not identify any concerning patterns of adverse events in pregnant women or their infants after hepatitis A vaccination (Havrix, Vaqta) or hepatitis A and B combined vaccination (Twinrix) during pregnancy.
  • Hepatitis A vaccine should be administered to pregnant women who are at high risk of exposure and to pregnant women who want protection according to the adult immunization schedule.


Prevention

Vaccination is the most effective way to prevent HBV infection. The consensus panel recommends HBV vaccination for the following adults:

  • People who are infected with HCV
  • People who are sexually active with or who share a household with a person with infectious HBV
  • Men who have sex with men (MSM)
  • People who inject drugs
  • People with occupational exposure to blood (e.g., medical care workers, dentists)
  • People who attend or work at institutions for people with developmental disabilities
  • Hemodialysis patients or those with end-stage renal disease
  • People who are infected with HIV
  • Anyone with liver disease
  • Anyone who lives in or travels to countries with high rates of HBV
  • Adults in correctional settings

Get a hepatitis A vaccine

  • Ask your doctor or nurse about hepatitis A vaccine.
    • The hepatitis A vaccine is given in 2 doses, 6 months apart. The vaccine is nearly 100% effective and has been a routine childhood vaccine in the United States since 2005.

Eat safe foods

Eat

  • Food that is cooked and served hot
  • Hard-cooked eggs
  • Fruits and vegetables you have washed in clean water or peeled yourself
  • Pasteurized dairy products

Don’t eat

  • Food served at room temperature
  • Food from street vendors
  • Raw or soft-cooked (runny) eggs
  • Raw or undercooked (rare) meat or fish
  • Unwashed or unpeeled raw fruits and vegetables
  • Peelings from fruit or vegetables
  • Condiments (such as salsa) made with fresh ingredients
  • Salads
  • Unpasteurized dairy products
  • ”Bushmeat” (monkeys, bats, or other wild game)

Drink safe beverages

Drink

  • Bottled water that is sealed (carbonated is safer)
  • Water that has been disinfected (boiled, filtered, treated)
  • Ice made with bottled or disinfected water
  • Carbonated drinks
  • Hot coffee or tea
  • Pasteurized milk

Don’t drink

  • Tap or well water
  • Ice made with tap or well water
  • Drinks made with tap or well water (such as reconstituted juice)
  • Flavored ice and popsicles
  • Unpasteurized milk

For more information see Food and Water Safety.

Practice hygiene and cleanliness

  • Wash your hands often.
  • If soap and water aren’t available, clean your hands with hand sanitizer (containing at least 60% alcohol).
  • Don’t touch your eyes, nose, or mouth. If you need to touch your face, make sure your hands are clean.
  • Try to avoid close contact, such as kissing, hugging, or sharing eating utensils or cups with people who are sick.

WHO Response

In May 2016, The World Health Assembly adopted the first “Global Health Sector Strategy on Viral Hepatitis, 2016-2021”. The strategy highlights the critical role of Universal Health Coverage and the targets of the strategy are aligned with those of the Sustainable Development Goals. The strategy has a vision of eliminating viral hepatitis as a public health problem and this is encapsulated in the global targets of reducing new viral hepatitis infections by 90% and reducing deaths due to viral hepatitis by 65% by 2030. Actions to be taken by countries and WHO Secretariat to reach these targets are outlined in the strategy.

To support countries in moving towards achieving the global hepatitis goals under the Sustainable Development Agenda 2030 WHO is working in the following areas:

  • raising awareness, promoting partnerships and mobilizing resources;
  • formulating evidence-based policy and data for action;
  • preventing transmission; and
  • scaling up screening, care and treatment services.

WHO published the “Progress report on HIV, viral hepatitis and sexually transmitted infections, 2019”, outlining its progress towards elimination. The report sets out global statistics on viral hepatitis B and C, the rate of new infections, the prevalence of chronic infections and mortality caused by these 2 high-burden viruses, as well as coverage of key interventions, all current as at the end of 2016 and 2017.

Since 2011, together with national governments, civil society and partners, WHO has organized annual World Hepatitis Day campaigns (as 1 of its 9 flagship annual health campaigns) to increase awareness and understanding of viral hepatitis. The date of 28 July was chosen because it is the birthday of Nobel-prize winning scientist Dr Baruch Bloomberg, who discovered the hepatitis B virus and developed a diagnostic test and vaccine for the virus.

For World Hepatitis Day 2019, WHO is focusing on the theme “Invest in eliminating hepatitis” to highlight the need for increased domestic and international funding to scale up hepatitis prevention, testing and treatment services, in order to achieve the 2030 elimination targets.


References

Hepatitis A


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