Hepatitis B virus (HBV), discovered in 1966, infects more than 350
million people in the world. The infection of HBV is a leading
cause of chronic carriage of the virus and progressive liver
diseases, such as hepatitis, liver cirrhosis and hepatocellular
carcinoma (HCC). HBV consists of a circular, partially
double-stranded DNA molecule of 3.2 kb in length, which contains
four overlapping reading frames that code for surface proteins
(HBsAg), core proteins (HBcAg/HBeAg), the viral polymerase, and the
transcriptional transactivator X protein. Chronic hepatitis appears
to be due to a suboptimal cellular immune response that destroys
some of the infected hepatocytes and does not purge the virus from
the remaining infected hepatocytes, thereby permitting the
persisting virus to trigger a chronic indolent necroinflammatory
liver disease that sets the stage for development of HCC. However,
the mechanisms responsible for malignant transformation in chronic
HBV infection are not well defined, and both viral and host factors
have been implicated in the process. All cases of HCC occur after
many years of chronic hepatitis which could, theoretically, provide
the mitogenic and mutagenic environment to precipitate random
genetic and chromosomal damage, and lead to the development of HCC.
Hepatitis B virus X protein (HBx), an important transforming
inducer, plays a crucial role in HCC development. HBx has the
capability to influence a variety of signal transduction pathways
within the cells. Monitoring of the HBV genotypes and antibody to
Hepatitis B x antigen (anti-HBx) are significant for predicting
early diagnosis of liver cirrhosis and HCC. HBV and Hepatitis C
virus or HIV coinfections can accelerate the course of chronic
liver disease and facilitate progression to cirrhosis and HCC. As
for therapy of liver diseases, five drugs are now FDA-approved for
the treatment of HBV, including interferon (IFN), lamivudine,
adefovir, entecavir, and peginterferon alfa-2a. Moreover, the
prevention for HBV infection is very important. It is likely that
the most important outcome of the research on HBV has been the
invention, development, and application of the vaccine against HBV.
However, at present most investigators focus on basic research
rather than practical applications. The HBV research should be
focused on animal models and clinical practice. The technology
update in HBV research and the multisubject combination may be
attached importance to next a few decades. Some molecular
approaches, such as antisense, oligonucleotides, ribozymes, RNA
interference targeting HBV mRNA, are available in antiviral
therapies.
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