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Hepatitis B virus (HBV) is a member of the family Hepadnaviridae, the members of which replicate in the liver and cause hepatic dysfunction. The only natural host for HBV appears to be humans, but the Hepadnaviridae family also includes viruses that infect woodchucks, ducks, ground squirrels, and herons.
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HBV has a small (3.2 kilobase) genome with a circular DNA that is partially double stranded and a retroviral replication strategy with an RNA intermediate. The genome codes for a surface glycoprotein, nucleocapsid protein, DNA polymerase, and the X protein, a small transcriptional transactivator that influences the transcription of HBV genes.1,2
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The complete HBV virion (Dane particle) is 42 nm in diameter and is composed of an outer lipoprotein coat containing the hepatitis B surface antigen (HBsAg) and a 27-nm nucleocapsid core, the hepatitis B core antigen (HBcAg). In addition to being a component of lipoprotein coat of the virus, HBsAg circulates independently in the blood as 22-nm spheres and tubules. HBsAg is antigenically heterogeneous, with a common antigen, a, and two pairs of mutually exclusive antigens, d and y, and w and r, resulting in four possible subtypes: adw, adr, ayw, and ayr.3,4 Antibodies to the a antigen confer immunity to all the subtypes. Although no clinical differences have been identified between subtypes, there are distinct geographic distributions, which have been useful in epidemiologic studies.5 A third hepatitis B antigen, the e antigen (HBeAg) is a soluble protein that is not part of the virus particle, but can be detected in the serum of patients with acute HBV infection, and in patients with chronic HBV infection who have high virus titers.
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HBV has a higher frequency of mutations than other DNA viruses due to its replication via an RNA intermediate, using a reverse transcriptase that seems to lack a proofreading function.4 The clinical significance of these mutations is not well established, but may include increased virulence, decreased host response to therapy, and viral replication in the presence of protective levels of antibody to HBsAg after vaccination or hepatitis B immune globulin (HBIG) administration.6,7
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HBV has been shown to retain infectivity in serum for at least 1 month when stored at either room temperature or frozen. HBV is also stable on environmental surfaces for 7 days or longer; thus, indirect inoculation of HBV can occur through inanimate objects.8,15 Infectivity is destroyed at 90°C after 1 hour.9
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CLINICAL ILLNESS, PATHOGENESIS, AND IMMUNE RESPONSE
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HBV infection can be asymptomatic, cause acute self-limited hepatitis, or result in fulminant hepatitis and death. Persons infected with HBV also may develop chronic infection, which can lead to chronic liver disease and death from cirrhosis or hepatocellular carcinoma (HCC).
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The incubation period for acute infection is an average of 90 days (range: 60–150 days) after exposure to HBV.8...