Chronic hepatitis B virus (HBV) infection remains an important global burden with an estimated 240 million HBV carriers worldwide and more than half a million people dying annually from the consequences of the HBV infection. Besides interferon and pegylated interferon, there are five antiviral drugs [lamivudine, adefovir (dipivoxil), entecavir, telbivudine, and tenofovir disoproxil fumarate] that have proved effective in the treatment of chronic hepatitis B. These five antiviral drugs interfere with viral DNA synthesis, which consists of a step reminiscent of the reverse transcriptase step in the replicative cycle of HIV. None of the antiviral drugs, or interferon, are capable of eradicating the covalently closed circular DNA, which remains settled as an episome within the virus-infected hepatocytes. In the short-term (1-3 years), the use of antiviral treatment is aimed at reducing viral DNA below levels of detection, whereas in the long term (10 years and, possibly, lifelong), treatment is aimed at reducing the progression to cirrhosis, hepatocellular carcinoma, liver decompensation, and death. As long as the virus can hide as the episomal covalently closed circular DNA, attempts to envisage a definite cure of the HBV infection may seem fortuitous.
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