| Hepatitis A |
| Classification and external resources |
Hepatitis A induced jaundice
|
| ICD-10 |
B15 |
| ICD-9 |
070.0, 070.1 |
| DiseasesDB |
5757 |
| MedlinePlus |
000278 |
| eMedicine |
med/991 ped/977 |
| MeSH |
D006506 |
Hepatitis A (formerly known as infectious hepatitis) is an acute infectious disease of the liver caused by the hepatitis A virus (HAV),[1] an RNA virus, usually spread by 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 HAV each year.[2] The time between infection and the appearance of the symptoms (the incubation period) is between two and six weeks and the average incubation period is 28 days.[3]
In developing countries, and in regions with poor hygiene standards, the incidence of infection with this virus is high[4] and the illness is usually contracted in early childhood. As incomes rise and access to clean water increases, the incidence of HAV decreases.[5] 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[3] 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 more than 80% of adults having symptoms compatible with acute viral hepatitis and the majority of children having either asymptomatic or unrecognized infection.[6] Antibody produced in response to HAV infection persists for life and confers protection against reinfection. The disease can be prevented by vaccination, and hepatitis A vaccines have been proven effective in controlling outbreaks worldwide.[3]
Contents
- 1 Signs and symptoms
- 2 Virology
- 2.1 Structure
- 2.2 Transmission
- 3 Diagnosis
- 4 Prevention
- 4.1 Vaccination programmes
- 5 Treatment
- 6 Prognosis
- 7 Epidemiology
- 8 References
- 9 External links
Signs and symptoms[edit source | 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.[7]
Symptoms usually last less than 2 months, although some people can be ill for as long as 6 months:[8]
- Fatigue
- Fever
- Nausea
- Appetite loss
- Jaundice, a yellowing of the skin or whites of the eyes due to hyperbilirubinemia
- Bile is removed from blood stream and excreted in urine, giving it a dark amber colour
- Clay-coloured feces
Virology[edit source | edit]
| Hepatitis A |
|
| Electron micrograph of hepatitis A virions. |
| Virus classification |
| Group: |
Group IV ((+)ssRNA) |
| Order: |
Picornavirales |
| Family: |
Picornaviridae |
| Genus: |
Hepatovirus |
| Species: |
Hepatitis A virus |
Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine.[9] 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 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 members of the Picornaviruses this virus requires an intact eukaryote initiating factor 4G (eIF4G) for the initiation of translation.[10] 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 cytotoxicity presumably because of the virus' own requirement for an intact eIF4G and liver pathology is likely immune-mediated.
Structure[edit source | edit]
The Hepatitis A virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a protein shell.[11] There is only one serotype of the virus, but multiple genotypes exist.[12] Codon use within the genome is biased and unusually distinct from its host. It also has a poor internal ribosome entry site.[13] In the region that codes for the HAV capsid, there are highly conserved clusters of rare codons that restrict antigenic variability.[14]
Transmission[edit source | 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 not uncommon,[15] and ingestion of shellfish cultivated in polluted water is associated with a high risk of infection.[16] Approximately 40% of all acute viral hepatitis is caused by HAV.[9] 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 there is lifelong immunity. 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).
Diagnosis[edit source | edit]
Serum IgG, IgM and ALT following Hepatitis A virus infection
Although HAV is excreted in the feces towards the end of the incubation period, specific diagnosis is made by the detection of HAV-specific IgM antibodies in the blood.[17] IgM antibody is only present in the blood following an acute 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 vaccination and tests for immunity to the virus are based on the detection of this antibody.[17]
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 enzyme comes from the liver cells that have been damaged by the virus.[18]
Hepatitis A virus is present in the blood (viremia) and feces of infected people up to two weeks before clinical illness develops.[18]
Prevention[edit source | edit]
For information about the vaccine, its properties, and its application, see Hepatitis A vaccine.
Hepatitis A can be prevented by vaccination, good hygiene and sanitation.[1][19]
There are two types of vaccines: one containing inactivated hepatitis A virus, and another containing a live but attenuated virus.[20] Both provide active immunity against a future infection. The vaccine protects against HAV in more than 95% of cases for longer than 25 years.[21] In the USA 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.[22]
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.[22]
Vaccination programmes[edit source | edit]
The vaccine was introduced in 1992 and was initially recommended for persons at high risk. Since then Bahrain and Israel have embarked on eradication programmes.[23] Australia, China, Belarus, Italy, Spain and the United States have started similar programmes. The incidence of Hepatitis A where widespread vaccination has been practised has decreased dramatically. In China and the United States the incidence of Hepatitis A has decreased by 90% since 1990.[24][25]
Treatment[edit source | edit]
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.[26]
Prognosis[edit source | edit]
The United States Centers for Disease Control and Prevention (CDC) in 1991 reported a low mortality rate for hepatitis A of 4 deaths per 1000 cases for the general population 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 that 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.[15]
Epidemiology[edit source | edit]
Hepatitis A Distribution 2005
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 had an intermediate or low level of endemicity in 2005. The countries in these regions may have an increasing burden of disease from hepatitis A.[27]
Globally, in 2010, acute hepatitis A resulted in 102,000 deaths which is slightly up from 99,000 in 1990.[28]
There were 30,000 cases of Hepatitis A reported to the CDC in the U.S. in 1997 and as many as 270,000 cases each year from 1980 through 2000. Approximately one third of the US population has been infected by Hepatitis A, most of whom go undiagnosed.[29]
Genotypes[edit source | edit]
Only one serotype and seven different genetic groups (four humans and three simian) have been described.[11] 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.[30] Genotype III has been isolated from both humans and owl monkeys. Most human isolates are of genotype I.[31] 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 substitution per site per year.[32][33] The human strains appear to have diverged from the simian ~3600 years ago.[citation needed] The mean age of genotypes III and IIIA strains has been estimated to be 592 and 202 years respectively.[citation needed]
Cases[edit source | edit]
The most widespread hepatitis A outbreak in the 2003 United States hepatitis outbreak afflicted at least 640 people (killing four) in north-eastern Ohio and south-western Pennsylvania in late 2003. The outbreak was blamed on tainted green onions at a restaurant in Monaca, Pennsylvania.[34][35] In 1988, more than 300,000 people in Shanghai, China were infected with HAV after eating clams (Anadara subcrenata) from a contaminated river.[9] In June 2013, frozen berries sold by US retailer Costco and purchased by around 240,000 people were the subject of a recall, after at least 158 people were infected with HAV, 69 of whom were hospitalized.[36][37]
References[edit source | edit]
- ^ a b Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 541–4. ISBN 0-8385-8529-9.
- ^ Wasley A, Fiore A, Bell BP (2006). "Hepatitis A in the era of vaccination". Epidemiol Rev 28: 101–11. doi:10.1093/epirev/mxj012. PMID 16775039.
- ^ a b c Connor BA (2005). "Hepatitis A vaccine in the last-minute traveler". Am. J. Med. 118 (Suppl 10A): 58S–62S. doi:10.1016/j.amjmed.2005.07.018. PMID 16271543.
- ^ Steffen R (October 2005). "Changing travel-related global epidemiology of hepatitis A". Am. J. Med. 118 (Suppl 10A): 46S–49S. doi:10.1016/j.amjmed.2005.07.016. PMID 16271541.
- ^ Jacobsen KH, Koopman JS (2005). "The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns". Int J Epidemiol 34 (3): 600–9. doi:10.1093/ije/dyi062. PMID 15831565.
- ^ Ciocca M. (2000). "Clinical course and consequences of hepatitis A infection". Vaccine 18: 71–4. doi:10.1016/S0264-410X(99)00470-3. PMID 10683554.
- ^ "Hepatitis A Symptoms". eMedicineHealth. 2007-05-17. Retrieved 2007-05-18.
- ^ "Hepatitis A Information for the Public". Center for Disease Control. 2009-09-17. Retrieved 2011-01-08.
- ^ a b c Murray, P. R., Rosenthal, K. S. & Pfaller, M. A. (2005) Medical Microbiology 5th ed., Elsevier Mosby.
- ^ Aragonès L, Guix S, Ribes E, Bosch A, Pintó RM (March 2010). "Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid". PLoS Pathog. 6 (3): e1000797. doi:10.1371/journal.ppat.1000797. PMC 2832697. PMID 20221432.
- ^ a b Cristina J, Costa-Mattioli M (August 2007). "Genetic variability and molecular evolution of hepatitis A virus". Virus Res. 127 (2): 151–7. doi:10.1016/j.virusres.2007.01.005. PMID 17328982.
- ^ Costa-Mattioli M, Di Napoli A, Ferré V, Billaudel S, Perez-Bercoff R, Cristina J (December 2003). "Genetic variability of hepatitis A virus". J. Gen. Virol. 84 (Pt 12): 3191–201. doi:10.1099/vir.0.19532-0. PMID 14645901.
- ^ Whetter LE, Day SP, Elroy-Stein O, Brown EA, Lemon SM (August 1994). "Low efficiency of the 5' nontranslated region of hepatitis A virus RNA in directing cap-independent translation in permissive monkey kidney cells". J. Virol. 68 (8): 5253–63. PMC 236470. PMID 8035522.
- ^ Aragonès L, Bosch A, Pintó RM (February 2008). "Hepatitis A virus mutant spectra under the selective pressure of monoclonal antibodies: codon usage constraints limit capsid variability". J. Virol. 82 (4): 1688–700. doi:10.1128/JVI.01842-07. PMC 2258700. PMID 18057242.
- ^ a b Brundage SC, Fitzpatrick AN (2006). "Hepatitis A". Am Fam Physician 73 (12): 2162–8. PMID 16848078.
- ^ Lees D (2000). "Viruses and bivalve shellfish". Int. J. Food Microbiol. 59 (1–2): 81–116. doi:10.1016/S0168-1605(00)00248-8. PMID 10946842.
- ^ a b Stapleton JT (1995). "Host immune response to hepatitis A virus". J. Infect. Dis. 171 (Suppl 1): S9–14. PMID 7876654.
- ^ a b Musana KA, Yale SH, Abdulkarim AS (2004). "Tests of Liver Injury". Clin Med Res 2 (2): 129–31. doi:10.3121/cmr.2.2.129. PMC 1069083. PMID 15931347.
- ^ http://www.nhs.uk/Conditions/Hepatitis-A/Pages/Prevention.aspx?url=Pages/What-is-it.aspx
- ^ Irving GJ, Holden J, Yang R, Pope D (2012). "Hepatitis A immunisation in persons not previously exposed to hepatitis A". Cochrane Database Syst Rev 7: CD009051. doi:10.1002/14651858.CD009051.pub2. PMID 22786522.
- ^ Nothdurft HD (July 2008). "Hepatitis A vaccines". Expert Rev Vaccines 7 (5): 535–45. doi:10.1586/14760584.7.5.535. PMID 18564009.
- ^ a b "Hepatitis A Vaccine: What you need to know". Vaccine Information Statement. CDC. 2006-03-21. Retrieved 2007-03-12.
- ^ André FE (2006). "Universal mass vaccination against hepatitis A.". Curr Top Microbiol Immunol 304: 95–114. PMID 16989266.
- ^ Cui F, Hadler SC, Zheng H, Wang F, Zhenhua W, Yuansheng H, Gong X, Chen Y, Liang X et al. (2009). "Hepatitis A surveillance and vaccine use in China from 1990 through 2007". J Epidemiol 19 (4): 189–195. doi:10.2188/jea.JE20080087. PMID 19561383.
- ^ Daniels D, Grytdal S, Wasley A (May 2009). "Surveillance for acute viral hepatitis - United States, 2007". MMWR Surveill Summ 58 (3): 1–27. PMID 19478727.
- ^ Hepatitis A PubMed Health
- ^ Jacobsen, KH; Wiersma, ST (2010 Sep 24). "Hepatitis A virus seroprevalence by age and world region, 1990 and 2005.". Vaccine 28 (41): 6653–7. PMID 20723630.
- ^ Lozano, R (2012 Dec 15). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.". Lancet 380 (9859): 2095–128. PMID 23245604.
- ^ Index | CDC Viral Hepatitis
- ^ Ching KZ, Nakano T, Chapman LE, Demby A, Robertson BH (January 2002). "Genetic characterization of wild-type genotype VII hepatitis A virus". J. Gen. Virol. 83 (Pt 1): 53–60. PMID 11752700.
- ^ de Paula VS, Baptista ML, Lampe E, Niel C, Gaspar AM (January 2002). "Characterization of hepatitis A virus isolates from subgenotypes IA and IB in Rio de Janeiro, Brazil". J. Med. Virol. 66 (1): 22–7. doi:10.1002/jmv.2106. PMID 11748654.
- ^ Moratorio G, Costa-Mattioli M, Piovani R, Romero H, Musto H, Cristina J (November 2007). "Bayesian coalescent inference of hepatitis A virus populations: evolutionary rates and patterns". J. Gen. Virol. 88 (Pt 11): 3039–42. doi:10.1099/vir.0.83038-0. PMID 17947528.
- ^ Kulkarni MA, Walimbe AM, Cherian S, Arankalle VA (December 2009). "Full length genomes of genotype IIIA Hepatitis A Virus strains (1995-2008) from India and estimates of the evolutionary rates and ages". Infect. Genet. Evol. 9 (6): 1287–94. doi:10.1016/j.meegid.2009.08.009. PMID 19723592.
- ^ "Hepatitis A outbreak associated with green onions at a restaurant--Monaca, Pennsylvania, 2003". MMWR Morb. Mortal. Wkly. Rep. 52 (47): 1155–7. November 2003. PMID 14647018.
- ^ Wheeler C, Vogt TM, Armstrong GL, et al. (September 2005). "An outbreak of hepatitis A associated with green onions". N. Engl. J. Med. 353 (9): 890–7. doi:10.1056/NEJMoa050855. PMID 16135833.
- ^ http://www.usatoday.com/story/news/nation/2013/06/18/hepatitis-a-frozen-berries-118-sick/2434267/
- ^ http://www.cdc.gov/hepatitis/Outbreaks/2013/A1b-03-31/index.html
External links[edit source | edit]
- CDC's hepatitis A links
- CDC's hepatitis A Fact Sheet
- Hepatitis A at the US National Library of Medicine Medical Subject Headings (MeSH)
- Hepatitis A virus at the US National Library of Medicine Medical Subject Headings (MeSH)
- Virus Pathogen Database and Analysis Resource (ViPR): Picornaviridae
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