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