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Tuesday 17 March 2009

Hepatitis B virus (HBV), the etiologic agent of "serum hepatitis," is a significant cause of acute and chronic liver disease worldwide.

HBV, a member of the hepadnavirus family, is a DNA virus that can be transmitted percutaneously (e.g., intravenous drug use or blood transfusion), perinatally, and sexually.

HBV has a unique replicative cycle. It synthesizes its DNA genome by reverse transcription of an RNA template. The lack of proofreading function of the reverse transcriptase results in a high mutation rate for HBV and creates an opportunity for selection of mutants that have an advantage for growth or avoidance of immune recognition.

Progeny viral DNA can integrate into the host genome, and this is associated with rearrangement of viral and host flanking sequences that can affect viral and host gene expression.

HBV infects hepatocytes, and cellular injury occurs mainly due to the immune response to infected liver cells and not to cytopathic effects of the virus.

HBV may evade immune defenses by inhibiting IFN-β production and by downregulating viral gene expression.

The effectiveness of the CTL response is a major determinant of whether a person clears the virus or becomes a chronic carrier. When infected hepatocytes are destroyed by CTLs, replicating virus is also eliminated and the infection is cleared.

However, if the rate of infection of hepatocytes outpaces the ability of CTLs to eliminate infected cells, a chronic infection is established.

This may happen in 5% to 10% of adults and up to 90% of children infected perinatally. In this setting, the liver develops a chronic hepatitis, with lymphocytic inflammation, apoptotic hepatocytes resulting from CTL-mediated killing, and progressive destruction of the liver parenchyma.

Viral mutants arise during chronic infection, and it has been hypothesized that these might modulate the severity of disease by changing the expression of certain immunogenic epitopes or altering viral replication levels. Long-term viral replication can lead to cirrhosis of the liver and an increased risk for hepatocellular carcinoma.

In some infected individuals, hepatocytes are infected but the CTL response is dormant, resulting in the establishment of a "carrier" state, without progressive liver damage.