Hepatitis B

Hepatitis B virus Template:Taxobox begin placement virus Template:Taxobox group vii entry
Family:	Hepadnaviridae
Genus:	Orthohepadnavirus
Species:	Hepatitis B virus

|} Originally known as serum hepatitis, Hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa. Hepatitis B is recognized as endemic in China and various other parts of Asia. Over one-third of the world's population has been or is actively infected by hepatitis B virus (acronym HBV).

Contents

1 Molecular Biology

Molecular Biology

The Hepatitis B virus is a member of the Hepadnavirus family. It consists of a proteinaceous core particle containing the viral genome in the form of double standed DNA and an outer lipid-based envelope with embedded proteins. The envelope proteins are involved in viral binding and release into susceptible cells. The inner capsid relocates the DNA genome to the cell's nucleus where viral mRNAs are transcribed. Three subgenomic transcripts encoding the envelope proteins are made, along with a poorly understood transcript encoding the X protein, whose function is still under debate. A fourth pre-genomic RNA is transcribed, which is exported to the cytosol and translates the viral polymerase and core proteins. Polymerase and pre-genomic RNA are encapsidated in assembling core particles, where reverse transcription of the pre-genomic RNA to genomic DNA occurs by the polymerase protein. The mature core particle then exits the cell via normal secretory pathways, acquiring an envelope along the way.

Hepatitis B is one of a few known non-retroviral viruses which employ reverse transcription as part of its replication process. Other viruses which use reverse transcription include HTLV or HIV, the virus that causes AIDS, but HIV and Hepatitis B are not related. Hepatitis B's genome is DNA, and reverse transcription is one of the latter steps in making new viral particles, whereas HIV has an RNA genome and reverse transcription is one of the first steps in replication.

Transmission

Hepatitis B is largely transmitted through exposure to bodily fluids containing the virus. This includes unprotected sexual contact, blood transfusions, re-use of contaminated needles and syringes, vertical transmission from mother to child during childbirth, and so on. The primary method of transmission depends on the prevalence of the disease in a given area. In low prevalence areas, such as the continental United States, IV drug abuse and unprotected sex are the primary method. In moderate prevalence areas, the disease is predominantly spread among children. In high prevalence countries, such as China, vertical transmission is most common. Without intervention, a mother who is positive for the Hepatitis B surface antigen confers a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for the hepatitis B e antigen.

Roughly 16-40% of unimmunized sexual partners of individuals with hepatitis B will be infected through sexual contact. The risk of transmission is closely related to the rate of viral replication in the infected individual at the time of exposure.

Complications

Hepatitis B infection may lead to a chronic inflammation of the liver, leading to cirrhosis. This type of infection dramatically increases the incidence of liver cancer.

The greater a person's age at the time of infection, the greater the chance their body will 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 neonates that acquire the infection from their mother at birth will clear the infection. Seventy percent of those infected between the age of one to six will clear the infection. When the infection is not cleared, one becomes a chronic carrier of the virus.

Hepatitis D infection requires a concomitant infection with hepatitis B. Co-infection with Hepatitis D increases the risk of liver cirrhosis and subsequently, liver cancer.

Diagnosis

The original assays for Hepatitis B involve serum tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex. The Hepatitis B surface antigen (HBsAg) is most frequently used to screen for the disease. It is the first detectable antigen to appear, 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. During this 'window' in which the host remains infected but is sucessfully clearing the virus, antibodies to the Hepatitis B core antigen (anti-HBc IGM) may the the only serologic evidence of disease.

Shortly after the appearace of the HBsAg, the Hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a hosts serum is associated with much higher rates of viral replication, however, some variants of the hepatitis B virus do not produce the 'e' antigen at all, 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 afterward. This conversion is usually associated with a dramatic decline in viral replication. If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by antibodies to the hepatitis B surface antigen (anti-HBs). A person negative for HBsAg but positive for anti-HBs has either cleared an infection or has been vaccinated previously.

More recently, PCR tests have been developed that allow quantization of viral load and is useful to assess a persons status and monitor treatment.

Treatment

There are currently several treatments for chronic hepatitis B that can increase a person's chance of clearing the infection. Treatments are available in the form of antivirals such as lamivudine and adefovir and immune system modulators such as interferon alpha. There are several other antivirals under investigation. Roughly, all of the currently available treatments, when used alone, are about equally efficacious. However, some individuals are much more likely to respond than others. It is not presently known if combination therapy offers any advantages. In general, each works by reducing the viral load by several orders of magnitude thus helping a body's immune system clear the infection. Treatment strategies should be individualized by a doctor and patient. Considerations include the risks associated with each treatment, a person's likelihood of clearing the virus with treatment, a person's risk for developing complications of persistent infection, and development of viral resistance with treatment.

Chronic carriers should be strongly encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and hepatocellular carcinoma (liver cancer).

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 also allows a mother to safely breastfeed her child.

An individual exposed to the virus that has never been vaccinated may also be treated with HBIG just after the exposure. For instance, a health care worker accidentally stuck by a needle used in a hepatitis B carrier would qualify. Treatment must be soon after exposure, however.

Prevention

A recombinant vaccine is available to prevent hepatitis B.

Many countries now routinely vaccinate infants against hepatitis B. In many areas, vaccination against hepatitis B is also required for all healthcare workers. Booster doses are recommended every five to ten years for healthcare workers.