Chronic HBV infection can lead to advanced liver disease, including cirrhosis and hepatocellular carcinoma. Hepatitis B is viewed as a specific immunity-mediated liver disease. Control of covalently closed circular DNA (cccDNA) amplification is an important feature necessary for the ability of hepadnaviruses to persistently infect cells, without cytopathic effects. The high level of viral replication and cccDNA copy number induce cytopathic changes in both cell culture and the livers of infected animals. HBV replication may also disturb intracellular organelles, causing ER stress and alteration of mitochondrial function and increased replication may lead to depletion of cellular molecular resources like phospholipids that are needed for synthesis of cellular membrane, lipoproteins, and HBV sub and full viral particles. Liver injury can be caused not only by high levels of viral replication in infected hepatocytes, but also by the accumulation of the viral proteins in the absence of HBV replication in hepatocytes. Accumulation of viral proteins does occur in livers of patients with chronic HBV infection.


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