Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma

Figure 1 Hepatitis B virus immune tolerance mechanism. In hepatocyte, hepatitis B virus (HBV) inhibits toll-like receptors mediated interferon (IFN)-α/β production by blocking the activation of interferon regulatory factor 3 HBV interferes with the retinoic acid-inducible gene-I (RIG-I) signaling pathway in hepatocyte and inhibits the production of IFN-α/β by disrupting the interaction between mitochondrial antiviral-signaling protein and RIG-I. HBV affects the activation of natural killer (NK) cells by inhibiting the production of interleukin (IL)-18 by macrophages. HBV promotes the generation of Tregs, which release IL-10 and transforming growth factor β to increase the expression of surface inhibitory receptors on NK cells and CD8 + T cells, thereby reducing IFN and tumor necrosis factor-α release. The expression of immune checkpoints on the surface of CD8 + T cells increases, leading to T cell exhaustion, resulting in immune tolerance of HBV. IL: Interleukin; HBV: Hepatitis B virus; NK: Natural killer; IFN: Interferon; NKG2A: Natural killer group 2A; NKG2D: Natural killer group 2D; Tim-3: T-cell immunoglobulin and mucin domain-containing protein 3; DC: Dendritic cell; CD: Cluster of differentiation; PD-1: Programmed death-1; CTLA4: Cytotoxic T lymphocyte-associated protein 4; TGF: Transforming growth factor; PD-L1: Programmed cell death 1 ligand 1; TNF: Tumor necrosis factor; TLR: Toll-like receptors; IRF-3: Interferon regulatory factor 3; IPS-1: Interferon-β promoter stimulator 1; RIG-I: Retinoic acid-inducible gene-I.