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| == Symptoms and complications ==
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| Hepatitis B virus infection may either be acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months.
| | <div style="font-size: 90%;"> |
| | {{Familytree/start}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | A01 | | | | | | | | | | |A01={{F1|B-cell neoplasms}}}} |
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| | {{Familytree|boxstyle=border: 0;| | | | | B01 | | | | | | | | B02 | | | | | |B01={{F1|CD5+}}|B02={{F1|CD5-}}}} |
| | {{Familytree|boxstyle=border: 0;| | |,|-|-|^|-|-|.| | | | | | |!| | | | | | |}} |
| | {{Familytree|boxstyle=border: 0;| | C01 | | | | C02 | | | | | C03 | | | | | |C01={{F1|CCND1+}}|C02={{F1|CCND1-}}|C03={{F1|DLBCL}}}} |
| | {{Familytree|boxstyle=border: 0;| | |!| | | | | |!| | | |,|-|-|^|-|-|-|-|-|-|.| | | |}} |
| | {{Familytree|boxstyle=border: 0;| | D01 | | | | D02 | | D03 | | | | | | | | D04 | | |D01={{F2|Pleomorphic MCL}}|D02={{F2|DLBCL, NOS CD5+}}|D03={{F1|CD10+}}|D04={{F1|CD10-}}}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | |!| | | | | | | | | |!| | | |}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | E01 | | | | |,|-|-|-|+|-|-|-|.| | | |E01={{F2|DLBCL, NOS GCB type}}}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | F01 | | F02 | | F03 | | |F01={{F1|BCL6+ IRF4/MUM1-}}|F02={{F1|BCL6+ IRF4/MUM1+}}|F03={{F1|BCL6- IRF4/MUM1+}}}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | |!| | | |!| | | |!| | | |}} |
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | G01 | | G02 | | G03 | | |G01={{F2|DLBCL, NOS GCB type}}|G02={{F2|Non-GCB}}|G03={{F2|Post-GCB}}}} |
| | {{Familytree/end}} |
| | </div> |
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| Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, only 5% of newborns that acquire the infection from their mother at birth will clear the infection. Of those infected between the age of one to six, 70% will clear the infection.<ref name="pmid16176431">{{cite journal |author=Kerkar N |title=Hepatitis B in children: complexities in management |journal=Pediatric transplantation |volume=9 |issue=5 |pages=685–91 |year=2005 |pmid=16176431 |doi=10.1111/j.1399-3046.2005.00393.x}}</ref>
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| Acute infection with hepatitis B virus is associated with acute viral [[hepatitis]] - an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, dark urine, and then progresses to development of [[jaundice]]. It has been noted that itchy skin has been an indication as a possible symptom of all hepatitis virus types. The illness lasts for a few weeks and then gradually improves in most affected people. A few patients may have more severe liver disease ([[fulminant hepatic failure]]), and may die as a result of it. The infection may be entirely asymptomatic and may go unrecognized.
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| Chronic infection with hepatitis B virus may be either asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to [[cirrhosis]] over a period of several years. This type of infection dramatically increases the incidence of [[hepatocellular carcinoma]] (liver cancer). Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for [[cirrhosis]] and liver cancer.
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| [[Hepatitis D]] infection can only occur with a concomitant infection with Hepatitis B virus because the Hepatitis D virus uses the Hepatitis B virus surface antigen to form a capsid.<ref name="pmid16364738">{{cite journal |author=Taylor JM |title=Hepatitis delta virus |journal=Virology |volume=344 |issue=1 |pages=71–6 |year=2006 |pmid=16364738 |doi=10.1016/j.virol.2005.09.033}}</ref> Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.<ref name="pmid1661197">{{cite journal |author=Oliveri F, Brunetto MR, Actis GC, Bonino F |title=Pathobiology of chronic hepatitis virus infection and hepatocellular carcinoma (HCC) |journal=The Italian journal of gastroenterology |volume=23 |issue=8 |pages=498–502 |year=1991 |pmid=1661197 |doi=}}</ref> ''[[Polyarteritis nodosa]]'' is more common in people with hepatitis B infection.
| | ===Use of Immunophenotyping/Genetic Testing in Differential Diagnosis of Mature B-Cell and NK/T-Cell Neoplasms=== |
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| == Diagnosis == | | <div style="font-size: 80%;"><BR> |
| [[Image:HBV serum markers.png|left|thumb|400px|Hepatitis B viral antigens and antibodies detectable in the blood following acute infection.]]
| | {{Familytree/start}} |
| [[Image:Chronic HBV v2.png|left|thumb|400px|Hepatitis B viral antigens and antibodies detectable in the blood of a chronically infected person]]
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | A01 | | | | | | | | | | |A01={{F1|B-cell neoplasms}}}} |
| The tests, called [[assay]]s, for detection of hepatitis B virus infection involve [[blood plasma|serum]] or [[blood test]]s that detect either viral antigens (proteins produced by the virus) or [[antibody|antibodies]] produced by the host. Interpretation of these assays is complex.<ref name="pmid3331068">{{cite journal |author=Bonino F, Chiaberge E, Maran E, Piantino P |title=Serological markers of HBV infectivity |journal=Ann. Ist. Super. Sanita |volume=24 |issue=2 |pages=217–23 |year=1987 |pmid=3331068 |doi=}}</ref>
| | {{Familytree|boxstyle=border: 0;| | | | | |,|-|-|-|-|^|-|-|-|-|.| | | | | | |}} |
| | | {{Familytree|boxstyle=border: 0;| | | | | B01 | | | | | | | | B02 | | | | | |B01={{F1|CD5+}}|B02={{F1|CD5-}}}} |
| The hepatitis B surface antigen (''HBsAg'') is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or ''HBcAg''. During this 'window' in which the host remains infected but is successfully clearing the virus, [[IgM]] antibodies to the hepatitis B core antigen (''anti-HBc IgM'') may be the only serological evidence of disease.
| | {{Familytree|boxstyle=border: 0;| | |,|-|-|^|-|-|.| | | | | | |!| | | | | | |}} |
| | | {{Familytree|boxstyle=border: 0;| | C01 | | | | C02 | | | | | C03 | | | | | |C01={{F1|CCND1+}}|C02={{F1|CCND1-}}|C03={{F1|DLBCL}}}} |
| Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (''HBeAg'') will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (''anti-HBe'') will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication.
| | {{Familytree|boxstyle=border: 0;| | |!| | | | | |!| | | |,|-|-|^|-|-|-|-|-|-|.| | | |}} |
| | | {{Familytree|boxstyle=border: 0;| | D01 | | | | D02 | | D03 | | | | | | | | D04 | | |D01={{F2|Pleomorphic MCL}}|D02={{F2|DLBCL, NOS CD5+}}|D03={{F1|CD10+}}|D04={{F1|CD10-}}}} |
| If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by [[IgG]] antibodies to the hepatitis B surface antigen and core antigen, (''anti-HBs'' and ''anti HBc IgG'').<ref name=Baron /> A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | |!| | | | | | | | | |!| | | |}} |
| | | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | E01 | | | | |,|-|-|-|+|-|-|-|.| | | |E01={{F2|DLBCL, NOS GCB type}}}} |
| Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers.<ref name="pmid17256718">{{cite journal |author=Lok AS, McMahon BJ |title=Chronic hepatitis B |journal=Hepatology |volume=45 |issue=2 |pages=507–39 |year=2007 |pmid=17256718 |doi=10.1002/hep.21513}}</ref> Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum [[alanine aminotransferase]] levels and inflammation of the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others.<ref name="pmid17935720">{{cite journal |author=Chu CM, Liaw YF |title=Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B |journal=Gastroenterology |volume=133 |issue=5 |pages=1458–65 |year=2007 |pmid=17935720 |doi=10.1053/j.gastro.2007.08.039}}</ref>
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | F01 | | F02 | | F03 | | |F01={{F1|BCL6+ IRF4/MUM1-}}|F02={{F1|BCL6+ IRF4/MUM1+}}|F03={{F1|BCL6- IRF4/MUM1+}}}} |
| | | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | |!| | | |!| | | |!| | | |}} |
| More recently, [[PCR]] tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens. These tests are called [[viral load]]s and are used to assess a person's infection status and to monitor treatment.<ref name="pmid17051445">{{cite journal |author=Zoulim F |title=New nucleic acid diagnostic tests in viral hepatitis |journal=Semin. Liver Dis. |volume=26 |issue=4 |pages=309–17 |year=2006 |pmid=17051445 |doi=10.1055/s-2006-951602}}</ref>
| | {{Familytree|boxstyle=border: 0;| | | | | | | | | | | | | | | | | | G01 | | G02 | | G03 | | |G01={{F2|DLBCL, NOS GCB type}}|G02={{F2|Non-GCB}}|G03={{F2|Post-GCB}}}} |
| | | {{Familytree/end}} |
| == Treatment ==
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| Hepatitis B infection does not usually require treatment because most adults clear the infection spontaneously.<ref name="pmid17129820">{{cite journal |author=Hollinger FB, Lau DT |title=Hepatitis B: the pathway to recovery through treatment |journal=Gastroenterol. Clin. North Am. |volume=35 |issue=4 |pages=895–931 |year=2006 |pmid=17129820 |doi=10.1016/j.gtc.2006.10.002}}</ref> Early antiviral treatment may only be required in fewer than 1% of patients, whose infection takes a very aggressive course ("fulminant hepatitis") or who are [[immunocompromised]]. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum [[alanine aminotransferase]], a marker of liver damage, and HBV DNA levels are candidates for therapy.<ref name="pmid17606962">{{cite journal |author=Lai CL, Yuen MF |title=The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points |journal=Ann. Intern. Med. |volume=147 |issue=1 |pages=58–61 |year=2007 |pmid=17606962 |doi=}}</ref>
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| Although none of the available drugs can clear the infection, they can stop the virus from replicating, and prevent liver damage such as cirrhosis and liver cancer. Treatments include [[Antiviral drug|antiviral]] drugs such as [[lamivudine]], [[adefovir]] and [[entecavir]], and [[immune system]] modulators such as [[Interferon|interferon alpha]]. However, some individuals are much more likely to respond than others and this might be because of the [[genotype]] of the infecting virus or the patient's heredity. The treatment works by reducing the [[viral load]], (the amount of virus particles as measured in the blood), which in turn reduces viral replication in the liver.
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| On March 29, 2005, the US [[Food and Drug Administration]] (FDA) approved [[Entecavir]] for the treatment of Hepatitis B.<ref>U.S. Food and Drug Administration. March 30, 2005. [http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01348.html FDA Talk Paper: FDA Approves New Treatment for Chronic Hepatitis B]. fda.gov. Retrieved on [[September 11]], [[2007]].</ref>
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| On February 25, 2005, the [[EU Commission]] approved Pegasys.<ref name="pmid16107195">{{cite journal |author=Hui CK, Lau GK |title=Peginterferon-alpha2a (40 kDa) (Pegasys) for hepatitis B |journal=Expert review of anti-infective therapy |volume=3 |issue=4 |pages=495–504 |year=2005 |pmid=16107195 |doi=10.1586/14787210.3.4.495}}</ref><ref>February 25, 2005. [http://www.roche.com/med-cor-2005-02-25 Pegasys approved in the European Union for the treatment of chronic hepatitis B: Only pegylated interferon approved for the treatment of chronic hepatitis B Retrieved on [[September 11]], [[2007]].</ref>
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| On October 27, [[2006]], [[telbivudine]] gained FDA approval. It is marketed under the brand name [[Tyzeka]] in the US and Sebivo outside the US. It is approved in [[Switzerland]].<ref>October 27, 2006. [http://www.hivandhepatitis.com/hep_b/news/2006/102706_a.html FDA Approves Telbivudine for Treatment of Chronic Hepatitis B]. hivandhepatitis.com. Retrieved on [[September 11]], [[2007]].</ref>
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| Infants born to mothers known to carry hepatitis B can be treated with antibodies to the hepatitis B virus (hepatitis B immune globulin or HBIg). When given with the vaccine within twelve hours of birth, the risk of acquiring hepatitis B is reduced 95%. This treatment allows a mother to safely breastfeed her child.
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| == Vaccination ==
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| {{main|Hepatitis B vaccine}} | |
| [[Image:HBsAg.jpg|left|thumb|200px|HBsAg]]
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| Several [[vaccines]] have been developed for the prevention of hepatitis B virus infection. These rely on the use of one of the viral envelope proteins (hepatitis B surface antigen or HBsAg). The vaccine was originally prepared from plasma obtained from patients who had long-standing hepatitis B virus infection. However, currently, these are more often made using [[recombinant DNA]] technology, though plasma-derived vaccines continue to be used; the two types of vaccines are equally effective and safe.<ref name="pmid16940869">{{cite journal |author=Zuckerman JN |title=Vaccination against hepatitis A and B: developments, deployment and delusions |journal=Curr. Opin. Infect. Dis. |volume=19 |issue=5 |pages=456–9 |year=2006 |pmid=16940869 |doi=10.1097/01.qco.0000244051.23511.09}}</ref>
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| Following vaccination Hepatitis B Surface antigen may be detected in serum for several days this is known as vaccine antigenaemia.<ref name="pmid15301037">{{cite journal |author=Martín-Ancel A, Casas ML, Bonet B |title=Implications of postvaccination hepatitis B surface antigenemia in the management of exposures to body fluids |journal=Infect Control Hosp Epidemiol |volume=25 |issue=7 |pages=611–3 |year=2004 |pmid=15301037 |doi=}}</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-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>{{cite journal |author=Kay A, Zoulim F |title=Hepatitis B virus genetic variability and evolution |journal=Virus Res. |volume=127 |issue=2 |pages=164–76 |year=2007 |pmid=17383765}}</ref> The negative-sense, (non-coding), is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the 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 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, polypeptides 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 J. Gastroenterol. |volume=13 |issue=1 |pages=48–64 |year=2007 |pmid=17206754 |doi=}}</ref> The function of the protein coded for by gene X is not fully understood.<ref name="pmid15542625">{{cite journal |author=Bouchard MJ, Schneider RJ |title=The enigmatic X gene of hepatitis B virus |journal=J. Virol. |volume=78 |issue=23 |pages=12725–34 |year=2004 |pmid=15542625 |doi=10.1128/JVI.78.23.12725-12734.2004}}</ref>
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| Hepatitis B virus (HBV) is a member of the [[Hepadnaviridae|Hepadnavirus family]].<ref name=Baron>{{cite book | author = Zuckerman AJ | title = Hepatitis Viruses. ''In:'' Baron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3738 | id = 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=Semin. Liver Dis. |volume=24 Suppl 1 |issue= |pages=3–10 |year=2004 |pmid=15192795 |doi=10.1055/s-2004-828672}}</ref> The outer envelope contains embedded proteins which 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 42nm, 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=J. Gen. Virol. |volume=67 ( Pt 7) |issue= |pages=1215–35 |year=1986 |pmid=3014045 |doi=}}</ref>
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| The hepatitis B surface antigen (''HBsAg'') is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of core protein, alternatively known as hepatitis B core antigen, or ''HBcAg''. During this 'window' in which the host remains infected but is successfully clearing the virus, [[IgM]] antibodies to the hepatitis B core antigen (''anti-HBc IgM'') may be the only serological evidence of disease.
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| Shortly after the appearance of the HBsAg, another antigen named as the hepatitis B e antigen (''HBeAg'') will appear. Traditionally, the presence of HBeAg in a host's serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the 'e' antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the 'e' antigen (''anti-HBe'') will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication.
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| If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by [[IgG]] antibodies to the hepatitis B surface antigen and core antigen, (''anti-HBs'' and ''anti HBc IgG'').<ref name=Baron /> A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.
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| Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers.<ref name="pmid17256718">{{cite journal |author=Lok AS, McMahon BJ |title=Chronic hepatitis B |journal=Hepatology |volume=45 |issue=2 |pages=507–39 |year=2007 |pmid=17256718 |doi=10.1002/hep.21513}}</ref> Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum [[alanine aminotransferase]] levels and inflammation of the liver, as revealed by biopsy. Carriers who have seroconverted to HBeAg negative status, particularly those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others.<ref name="pmid17935720">{{cite journal |author=Chu CM, Liaw YF |title=Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B |journal=Gastroenterology |volume=133 |issue=5 |pages=1458–65 |year=2007 |pmid=17935720 |doi=10.1053/j.gastro.2007.08.039}}</ref>
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| More recently, [[PCR]] tests have been developed to detect and measure the amount of viral nucleic acid in clinical specimens. These tests are called [[viral load]]s and are used to assess a person's infection status and to monitor treatment.<ref name="pmid17051445">{{cite journal |author=Zoulim F |title=New nucleic acid diagnostic tests in viral hepatitis |journal=Semin. Liver Dis. |volume=26 |issue=4 |pages=309–17 |year=2006 |pmid=17051445 |doi=10.1055/s-2006-951602}}</ref>
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| The three standard blood tests for hepatitis B can determine if a person is currently infected with [[HBV]], has recovered, is a chronic carrier, or is susceptible to [[HBV infection]]:<ref name=WHO1>{{cite web | title = Hepatitis B | url = http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index3.html }}</ref>
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