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Hepatitis B virus

Micro > Virology > DNA viruses
Hepatitis B virus (HBV)

Hepatitis B is an icosahedral, enveloped, double stranded circular DNA virus. It belongs to the Hepadnaviridae family.  It is transmitted through blood, sexual contact, or transplacentally.  The genome is partially RNA and partially DNA. To help with replication, it contains a reverse transcriptase enzyme (i.e. an RNA-dependent DNA polymerase). [in this way it is similar to HIV, and thus some medications active against HIV may be active against hepatitis B]. Upon infection, it travels in the blood to hepatocytes where it replicates by completing the partially dsDNA viral genome via viral DNA polymerase; now complete dsDNA generates mRNA transcripts; mRNA produces viral proteins; mRNA is also used to make partially dsDNA via the reverse transcriptase; partially dsDNA is packaged and particles bud through cell membrane.

Hepatitis b can result in acute or chronic hepatitis, though a majority of infections are asymptomatic. In acute hepatitis, viral antigens on infected hepatocytes activate cytotoxic T-lymphocytes, leading to inflammation and necrosis of hepatocytes.  This will result in jaundice and fever.

In the US, needle sharing and sexual transmission are the most common modes of transmission, while vertical transmission is seen mostly outside the US.  Transmission through blood products is most common outside the US, where there may be inadequate screening. Transmission can occur after occupational exposure to infected blood or blood products.  Chronic infection/inflammation of hepatocytes may cause cirrhosis and increased risk for hepatocellular carcinoma (especially in hosts with weak immune response (e.g. infants) because infected hepatocytes are not cleared and the virus persists in carrier state).

Diagnosis is through clinical acumen and serology. Serology testing consist of Hepatitis B surface antigen (HBsAg), which can appear prior to symptoms, or abnormal liver function tests (such as elevated ALT).  HBsAg is present in both acute and chronic infection.  Over the course of the infection, core antigen antibodies are produced while the surface antigen is still present.  Later on, the surface antigen disappears and is followed by the appearance of antibodies to surface antigen.  After resolution of the infection, anti-HBs and anti-HBc IgG will still remain. The presence of HBeAg indicates a high degree of infetiousness

The "window period" is a when HBsAg and HBsAb (e.g. anti-HBsAg) are both negative. Diagnosis during the window period requires detection of Hepatitis B Core Ab, or in some cases a positive Hepatitis B PCR.

In chronic infection, HBsAb never appears, and there is classically persistent + HBsAG, +/- HB core Ab, and a + PCR in the setting of chronic elevation of transaminases.

65% of infections are asymptomatic, 25% of infections may be acute with resolution, 1% may present as acute fulminant hepatitis (80% mortality), and 10% of infections are chronic active or chronic persistent. Chronic infection may lead to liver failure and/or hepatocellular carcinoma.

Co-infection of Hepatitis D with Hepatitis B leads to a more fulminant initial course. Superinfection of Hepatitis D superimposed on chronic Hepatitis B infection leads to an acute flare of hepatitis and a more fulminant course.

Treatment of HBV is dependent on the type of presentation. Supportive therapy is used for acute illness.    Lamivudine, tenofovir, adefovir, or other nucleoside analogs may be used in cases of chronic infection.

Prevention: A recombinant HBsAg vaccine can be administered to newborns and is recommended for all children in the US as well as adults at risk of infection. Post-exposure prophylaxis measures include Hepatitis B immune globulin (HBIG), which contain anti-HBsAg antibodies. Infants of HBsAg+ mothers are given HBIG immediately after birth, followed by Hepatitis B vaccination. Note that the strength of immune response determines clinical course of infection: A strong response produces a severe course that resolves quickly, whereas a weak response produces a mild but chronic course.
Related concepts
1.       Circular double stranded DNA
2.       Double stranded DNA virus
3.       Hepadnaviridae
4.       Hepatitis B virus
5.       Hepatitis
6.       HepB
7.       HBV
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