Hepatitis B virus (HBV) poses a major global health burden with 260 million people being chronically infected and 890,000 dying annually from complications in the course of the
infection. HBV is a small enveloped virus with a reverse-transcribed
DNA genome that infects hepatocytes and can cause acute and
chronic infections of the liver. HBV is endemic in humans and apes representing the prototype member of the viral family Hepadnaviridae and can be divided into 10 genotypes. Hepadnaviruses have been found in all vertebrate classes and constitute an ancient viral family that descended from non-enveloped progenitors more than 360 million years ago. The de novo emergence of the envelope
protein gene was accompanied with the liver-tropism and resulted in a tight virus-host association. The oldest HBV genomes so far have been isolated from
human remains of the Bronze Age and the Neolithic (~7000 years before present). Despite the remarkable stability of the hepadnaviral genome over geological eras, HBV is able to rapidly evolve within an infected individual under pressure of the immune response or during
antiviral treatment. Treatment with currently available
antivirals blocking intracellular replication of HBV allows controlling of high
viremia and improving liver health during long-term
therapy of patients with
chronic hepatitis B (CHB), but they are not sufficient to cure the disease. New
therapy options that cover all HBV genotypes and emerging viral variants will have to be developed soon. In addition to the
antiviral treatment of chronically infected patients, continued efforts to expand the global coverage of the currently available HBV
vaccine will be one of the key factors for controlling the rising global spread of HBV. Certain improvements of the
vaccine (e.g. inclusion of PreS domains) could counteract known problems such as low or no responsiveness of certain risk groups and waning anti-HBs titers leading to occult
infections, especially with HBV genotypes E or F. But even with an optimal
vaccine and a cure for
hepatitis B, global eradication of HBV would be difficult to achieve because of an existing viral reservoir in primates and bats carrying closely related hepadnaviruses with zoonotic potential.