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The hepatitis B virus covers both the molecular grounds of hepatitis B replication and gene expression "in vivo" and in model systems, and the clinical impact of genetic variants or immune response in chronic infection. This text emphasizes the molecular mechanisms underlying diseases associated with the virus, including liver carcinogenesis. It discusses their possible relevance to therapy and to the prevention of infection. It also discusses rational approaches to design novel vaccines or cytokine treatments, as well as strategies to develop vectors for liver-directed gene therapy.