Hepatitis B virus (HBV) causes both transient and chronic liver infections, with chronic infections potentially leading to liver cancer. Despite the availability of an effective vaccine, vaccination is not a treatment for established infections, and its high cost has hindered its introduction in many poorer countries. Treatment options for chronic infections have been limited, with alpha interferon therapy being effective in only a subset of carriers. More recent approaches involving nucleoside analogs and other inhibitors of virus replication show promise but require further evaluation. The persistence of chronic infections is attributed to the long-lived nature of hepatocytes and the stable virus-host cell interaction. Understanding the virus-host interactions is crucial for developing better treatments and reducing the incidence of hepatocellular cancer (HCC). The liver, composed primarily of hepatocytes, bile ductule epithelium, and Kupffer cells, plays a vital role in energy storage, blood homeostasis, chemical detoxification, and immunity. Hepatocytes are the primary target of HBV infection, and their continuous shedding of the virus into the bloodstream ensures the persistence of infection. The formation of cccDNA, the template for viral mRNA transcription, marks the initiation of infection. Viral gene expression is regulated by liver-specific transcription factors, and the viral proteins, including core, polymerase, and envelope proteins, are essential for viral replication and assembly. The assembly and reverse transcription processes involve the binding of the polymerase to the epsilon stem-loop structure on pgRNA, followed by RNA packaging and DNA synthesis. The regulation of cccDNA amplification is a key aspect of hepadnavirus replication, and the interaction between nucleocapsids and envelope proteins is thought to play a role in virion formation. Transient infections, which are common in adults, often involve the entire hepatocyte population but are rapidly cleared, raising questions about the immune response and virus clearance mechanisms.Hepatitis B virus (HBV) causes both transient and chronic liver infections, with chronic infections potentially leading to liver cancer. Despite the availability of an effective vaccine, vaccination is not a treatment for established infections, and its high cost has hindered its introduction in many poorer countries. Treatment options for chronic infections have been limited, with alpha interferon therapy being effective in only a subset of carriers. More recent approaches involving nucleoside analogs and other inhibitors of virus replication show promise but require further evaluation. The persistence of chronic infections is attributed to the long-lived nature of hepatocytes and the stable virus-host cell interaction. Understanding the virus-host interactions is crucial for developing better treatments and reducing the incidence of hepatocellular cancer (HCC). The liver, composed primarily of hepatocytes, bile ductule epithelium, and Kupffer cells, plays a vital role in energy storage, blood homeostasis, chemical detoxification, and immunity. Hepatocytes are the primary target of HBV infection, and their continuous shedding of the virus into the bloodstream ensures the persistence of infection. The formation of cccDNA, the template for viral mRNA transcription, marks the initiation of infection. Viral gene expression is regulated by liver-specific transcription factors, and the viral proteins, including core, polymerase, and envelope proteins, are essential for viral replication and assembly. The assembly and reverse transcription processes involve the binding of the polymerase to the epsilon stem-loop structure on pgRNA, followed by RNA packaging and DNA synthesis. The regulation of cccDNA amplification is a key aspect of hepadnavirus replication, and the interaction between nucleocapsids and envelope proteins is thought to play a role in virion formation. Transient infections, which are common in adults, often involve the entire hepatocyte population but are rapidly cleared, raising questions about the immune response and virus clearance mechanisms.