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Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, significant progress has been made in understanding the pathogenesis of the virus and creating an effective vaccine. In the past two decades, several antiviral therapies have reduced the incidence of HBV-related hepatocellular carcinoma. The nucleos(t)ide analogues have succeeded in decreasing the viral load to undetectable levels but have been unable to eradicate the virus due to the persistence of covalently closed circular DNA in the hepatocyte nucleus. Despite being on successful antiviral therapy for multiple years, patients are still at risk of developing hepatocellular carcinoma. Recently, a number of different drug targets have been identified that intervene on the viral replication cycle or host immune system. This chapter discusses the immunopathogenesis of the virus, the effectiveness of nucleos(t)ide analogues, and recent therapeutic developments. In light of robust progress achieved in antiviral therapy, the cure for hepatitis B is likely on the horizon.
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