FIGURE 4.

Impact of HBV-DNA integration in the achievement and assessment of HBV functional cure. In patients with an active HBV reservoir, HBsAg can derive from the transcriptional activity of cccDNA and from HBV-integrated DNA. HBsAg from integrated HBV-DNA can consequently contribute to the elevated burden of viral antigens and the subsequent exhaustion of anti-HBV immune response, potentially jeopardizing the achievement of HBV functional cure. In patients with a silenced HBV reservoir, HBsAg in serum can still be present deriving exclusively from integrated HBs-encoding regions, thus hampering the proper recognition of the achievement of HBV functional cure.