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| __NOTOC__
| | #REDIRECT[[Hepatitis B virus]] |
| {{Hepatitis B}}
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| {{CMG}}
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| ==Overview==
| | [[Category:Emergency mdicine]] |
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| ==Taxonomy==
| | [[Category:Up-To-Date]] |
| [[Viruses]]; Retro-transcribing viruses; [[Hepadnaviridae]]; Orthohepadnavirus | |
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| ==Causes==
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| For infants and children, the two primary sources of HBV infection are perinatal transmission from infected mothers and horizontal transmission from infected household contacts. Adolescents are at risk for HBV infection primarily through high-risk sexual activity (i.e., sex with more than one partner and male sexual activity with other males) and injection-drug use. Transmission of HBV via transfusion of blood and plasma-derived products is rare because of donor screening for HBsAg and viral inactivation procedures.
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| For a newborn infant whose mother is positive for both [[HBsAg]] and [[HBeAg]], the risk for chronic HBV infection is 70%--90% by age 6 months in the absence of postexposure immunoprophylaxis. For infants of women who are HBsAg positive but HBeAg negative, the risk for chronic infection is <10% in the absence of postexposure immunoprophylaxis. Rare cases of fulminant hepatitis B among perinatally infected infants also have been reported. Studies suggest that breastfeeding by an HBsAg-positive mother does not increase the risk for acquisition of HBV infection in the infant.
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| Children who are not infected at birth remain at risk from long-term interpersonal contact with their infected mothers. In one study, 38% of infants who were born to HBsAg-positive mothers and who were not infected perinatally became infected by age 4 years. In addition, children living with any chronically infected persons are at risk for becoming infected through percutaneous or mucosal exposures to blood or infectious body fluids (e.g., sharing a toothbrush, contact with exudates from dermatologic lesions, contact with HBsAg-contaminated surfaces). HBV transmission rates to susceptible household contacts of chronically infected persons have varied (range: 14%--60%). High rates of infection also have been reported among unvaccinated long-term residents of institutions for the mentally handicapped, and, in rare instances, person-to-person transmission has been reported in child care settings.
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| ==Virology==
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| ===Structure===
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| [[File:HBV Genome.png|left|thumb|The genome organisation of HBV. The genes overlap.]]
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| Hepatitis B virus (HBV) is a member of the [[Hepadnaviridae|Hepadnavirus family]].<ref name=Baron>{{Cite book |author=Zuckerman AJ |chapter=Hepatitis Viruses |title=Baron's Medical Microbiology |editor=Baron S, ''et al'' |edition=4th |publisher=University of Texas Medical Branch |year=1996|url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3738|isbn=0-9631172-1-1 }}</ref> The virus particle, ([[virion]]) consists of an outer [[lipid]] envelope and an [[icosahedron|icosahedral]] [[nucleocapsid]] core composed of [[protein]]. The nucleocapsid encloses the viral DNA and a DNA polymerase that has [[reverse transcriptase]] activity.<ref name="pmid15192795">{{cite journal |author=Locarnini S |title=Molecular virology of hepatitis B virus |journal=[[Seminars in Liver Disease]] |volume=24 Suppl 1 |issue= |pages=3–10 |year=2004 |pmid=15192795 |doi=10.1055/s-2004-828672 |url=http://www.thieme-connect.com/DOI/DOI?10.1055/s-2004-828672 |accessdate=2012-02-08}}</ref> The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses, with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen ([[HBsAg]]), and is produced in excess during the life cycle of the virus.<ref name="pmid3014045">{{cite journal |author=Howard CR |title=The biology of hepadnaviruses |journal=[[The Journal of General Virology]] |volume=67 ( Pt 7) |issue= |pages=1215–35 |year=1986 |month=July |pmid=3014045 |doi= |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=3014045 |accessdate=2012-02-08}}</ref>
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| ===Genome===
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| The [[genome]] of HBV is made of circular [[DNA]], but it is unusual because the DNA is not fully [[Double helix|double-stranded]]. One end of the full length strand is linked to the viral [[DNA polymerase]]. The genome is 3020–3320 [[nucleotides]] long (for the full-length strand) and 1700–2800 nucleotides long (for the short length-strand).<ref name="pmid17383765">{{cite journal |author=Kay A, Zoulim F |title=Hepatitis B virus genetic variability and evolution |journal=[[Virus Research]] |volume=127 |issue=2 |pages=164–76 |year=2007 |month=August |pmid=17383765 |doi=10.1016/j.virusres.2007.02.021 |url=http://linkinghub.elsevier.com/retrieve/pii/S0168-1702(07)00061-5 |accessdate=2012-02-08}}</ref> The negative-sense, (non-coding), is complementary to the viral [[Messenger RNA|mRNA]]. The viral DNA is found in the [[Nucleus (biology)|nucleus]] soon after infection of the [[Cell (biology)|cell]]. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a [[protein]] [[molecule]] from the (-) sense strand and a short sequence of [[RNA]] from the (+) sense strand. Non-coding bases are removed from the ends of the (-) sense strand and the ends are rejoined. There are four known genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start [[codon]] is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by [[Proteolysis|proteolytic]] processing of the pre-core protein. The DNA [[polymerase]] is encoded by gene P. Gene S is the gene that codes for the surface [[antigen]] (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, [[polypeptide]]s of three different sizes called large, middle, and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) are produced.<ref name="pmid17206754">{{cite journal |author=Beck J, Nassal M |title=Hepatitis B virus replication |journal=[[World Journal of Gastroenterology : WJG]] |volume=13 |issue=1 |pages=48–64 |year=2007 |month=January |pmid=17206754 |doi= |url=http://www.wjgnet.com/1007-9327/full/v13/i1/48.htm |accessdate=2012-02-08}}</ref> The function of the protein coded for by gene X is not fully understood but it is associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth regulating molecules.<ref>{{cite journal |author=Li W, Miao X, Qi Z, Zeng W, Liang J, Liang Z |title=Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2 |journal=Virol. J. |volume=7 |pages=45 |year=2010 |pmid=20170530 |pmc=2841080 |doi=10.1186/1743-422X-7-45 |url=http://www.virologyj.com/content/7//45}}</ref>
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| ===Replication===
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| [[File:HBV replication.png|left|thumb|Hepatitis B virus replication.]]
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| The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known pararetroviruses: non-[[retrovirus]]es that still do use [[reverse transcription]] in their replication process. The virus gains entry into the cell by binding to an unknown receptor on the surface and being [[endocytosis|endocytosed]] in. Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The partially double stranded viral DNA is then made fully double stranded and transformed into covalently closed circular DNA (cccDNA) that serves as a template for transcription of four viral [[mRNA]]s. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the [[capsid]] core protein and the viral [[DNA polymerase]]. These four viral transcripts undergo additional processing and go on to form progeny virions that are released from the cell or returned to the nucleus and re-cycled to produce even more copies. <ref name="pmid17206754">{{cite journal |author=Beck J, Nassal M |title=Hepatitis B virus replication |journal=[[World Journal of Gastroenterology : WJG]]|volume=13 |issue=1 |pages=48–64 |year=2007 |month=January |pmid=17206754 |doi= |url=http://www.wjgnet.com/1007-9327/full/v13/i1/48.htm |accessdate=2012-02-08}}</ref> <ref name="pmid17206755">{{cite journal |author=Bruss V |title=Hepatitis B virus morphogenesis |journal=[[World Journal of Gastroenterology : WJG]] |volume=13 |issue=1 |pages=65–73 |year=2007 |month=January |pmid=17206755 |doi= |url=http://www.wjgnet.com/1007-9327/full/v13/i1/65.htm |accessdate=2012-02-08}}</ref> The long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase activity.
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| ===Serotypes and Genotypes ===
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| The virus is divided into four major [[serotype]]s (adr, adw, ayr, ayw) based on antigenic [[epitope]]s presented on its envelope proteins, and into eight genotypes (A-H) according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination.<ref name="pmid15752827">{{cite journal |author=Kramvis A, Kew M, François G |title=Hepatitis B virus genotypes |journal=[[Vaccine]] |volume=23 |issue=19 |pages=2409–23 |year=2005 |month=March |pmid=15752827 |doi=10.1016/j.vaccine.2004.10.045 |url=http://linkinghub.elsevier.com/retrieve/pii/S0264-410X(04)00849-7 |accessdate=2012-02-08}}</ref><ref name="pmid8666521">{{cite journal |author=Magnius LO, Norder H |title=Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene |journal=[[Intervirology]] |volume=38 |issue=1-2 |pages=24–34 |year=1995 |pmid=8666521 |doi= |url= |accessdate=2012-02-08}}</ref>
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| Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A-F).<ref name="Norder1994">{{cite journal | author = Norder H, Courouce AM, Magnius LO | year = 1994 | title = Complete genomes, phylogenic relatedness and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes | journal = Virology | volume = 198 | issue = 2| pages = 489–503 | doi = 10.1006/viro.1994.1060 | pmid = 8291231 }}</ref> Two further types have since been described (G and H).<ref name="pmid15779062">{{cite journal |author=Shibayama T, Masuda G, Ajisawa A, Hiruma K, Tsuda F, Nishizawa T, Takahashi M, Okamoto H |title=Characterization of seven genotypes (A to E, G and H) of hepatitis B virus recovered from Japanese patients infected with human immunodeficiency virus type 1 |journal=Journal of Medical Virology |volume=76 |issue=1 |pages=24–32 |year=2005 |month=May |pmid=15779062 |doi=10.1002/jmv.20319 }}</ref> Most genotypes are now divided into subgenotypes with distinct properties.<ref name="pmid17206751">{{cite journal |author=Schaefer S |title=Hepatitis B virus taxonomy and hepatitis B virus genotypes |journal=World Journal of Gastroenterology : WJG |volume=13 |issue=1 |pages=14–21 |year=2007 |month=January |pmid=17206751 |url=http://www.wjgnet.com/1007-9327/13/14.asp }}</ref>
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| Genotype A is most commonly found in the Americas, Africa, India and Western Europe. Genotype B is most commonly found in Asia and the United States. Genotype B1 dominates in Japan, B2 in China and Vietnam while B3 confined to Indonesia. B4 is confined to Vietnam. All these strains specify the serotype ayw1. B5 is most common in the Philippines. Genotype C is most common in Asia and the United States. Subgenotype C1 is common in Japan, Korea and China. C2 is common in China, South-East Asia and Bangladesh and C3 in Oceania. All these strains specify the serotype adrq. C4 specifying ayw3 is found in Aborigines from Australia.<ref name="pmid20156297">{{cite journal |author=Kurbanov F, Tanaka Y, Mizokami M |title=Geographical and genetic diversity of the human hepatitis B virus |journal=Hepatology Research : the Official Journal of the Japan Society of Hepatology |volume=40 |issue=1 |pages=14–30 |year=2010 |month=January |pmid=20156297 |doi=10.1111/j.1872-034X.2009.00601.x }}</ref> Genotype D is most commonly found in Southern Europe, India and the United States and has been divided into 8 subtypes (D1–D8). In Turkey genotype D is also the most common type. A pattern of defined geographical distribution is less evident with D1–D4 where these subgenotypes are widely spread within Europe, Africa and Asia. This may be due to their divergence having occurred before than of genotypes B and C. D4 appears to be the oldest split and is still the dominating subgenotype of D in Oceania. Type E is most commonly found in West and Southern Africa. Type F is most commonly found in Central and South America and has been divided into two subgroups (F1 and F2). Genotype G has an insertion of 36 nucleotides in the core gene and is found in France and the United States.<ref name="Stuyver2000">{{cite journal |author=Stuyver L, De Gendt S, Van Geyt C, ''et al.'' |title=A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness |journal=J. Gen. Virol. |volume=81 |issue=Pt 1 |pages=67–74 |year=2000 |month=January |pmid=10640543 |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=10640543}}</ref> Type H is most commonly found in Central and South America and California in United States. Africa has five genotypes (A-E). Of these the predominant genotypes are A in Kenya, B and D in Egypt, D in Tunisia, A-D in South Africa and E in Nigeria.<ref name="pmid20156297"/> Genotype H is probably split off from genotype F within the New World.<ref name="Arauz-Ruiz2002">{{cite journal |author=Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO |title=Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America |journal=J. Gen. Virol. |volume=83 |issue=Pt 8 |pages=2059–73 |year=2002 |month=August |pmid=12124470 |url=http://vir.sgmjournals.org/cgi/pmidlookup?view=long&pmid=12124470}}</ref>
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| == References ==
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| {{Reflist|2}}
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| {{STD/STI}}
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| [[Category:Needs overview]]
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| [[Category:Hepatitis|B]]
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| [[Category:Viruses]]
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| [[Category:Infectious disease]] | | [[Category:Infectious disease]] |
| | [[Category:Hepatology]] |
| [[Category:Gastroenterology]] | | [[Category:Gastroenterology]] |
| [[Category:Mature chapter]]
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| [[Category:Disease]]
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| {{WH}}
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| {{WS}}
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