Hepatitis B virus (HBV)
infection has a multi-dimensional effect on the host, which not only alters the dynamics of immune response but also persists in the hepatocytes to predispose oncogenic factors. The virus exists in multiple forms of which the nuclear localized covalently closed
circular DNA (cccDNA) is the most stable and the primary reason for viral persistence even after clearance of
surface antigen and
viral DNA. The second reason is the existence of pregenomic
RNA (
pgRNA) containing virion particles. On the other hand, the integration of the viral genome in the host chromosome also leads to persistent production of
viral proteins along with the
chromosomal instabilities. The
interferon treatment or administration of nucleot(s)ide analogs leads to reduction in the
viral DNA load, but the
pgRNA and
surface antigen clearance are a slow process and complete loss of serological
HBsAg is rare. The prolonged exposure of immune cells to the
viral antigens, particularly HBs
antigen, in the blood circulation results in T-cell exhaustion, which disrupts immune clearance of the virus and virus-infected cells. In addition, it predisposes immune-tolerant microenvironment, which facilitates the
tumor progression. Thus cccDNA,
pgRNA, and
HBsAg along with the
viral DNA could be the therapeutic targets in the early disease stages that may improve the quality of life of
chronic hepatitis B patients by impeding the progression of the disease toward
hepatocellular carcinoma.