Table 1

Main factors that influence HBV persistence and pathogenesis

  • Immune-mediated factors:

    • Lack of robust type-1 IFN production

    • Weak CD8 T- and CD4 T-cell responses

    • NK-, NKT cell-mediated liver damage

  • Virological factors:

    • cccDNA stability

    • Interference with the innate immune system of the hepatocytes:

      • (a) HBeAg-mediated inhibition of TLR-2 signalling

      • (b) HBx-mediated inhibition of RIG-1 pathways

      • (c) SVPs-mediated inhibition of TLR-9 signalling

      • (d) Impairment of STAT translocation/methylation

    • Alteration of cellular pathways

      • (a) Cell-signalling pathways

      • (b) Mitochondria functions

      • (c) Lipid metabolism

      • (d) Epigenetic status of host genome

  • Emergence of HBV variants:

    • Induced by immune pressure (PC/BCP)

    • Induced by antiviral therapy with polymerase inhibitors

  • Co-infection with other viruses:

    • HBV/HCV

    • HBV/HDV

    • HBV/HIV