Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy

Figure 1 Mechanisms of hepatitis C virus-induced inflammation. Hepatitis C virus (HCV) RNA triggers Toll-like receptor mediated nuclear factor (NF)-κB activation and inflammatory cytokine release, while HCV proteins mainly lead to oxidative and endoplasmic reticulum stress and potassium efflux, causing the Nod-like receptor pyrin domain containing inflammasome activation. The released inflammatory factors bind to their corresponding receptors and then directly induce NF-κB activation or indirectly lead to signalling pathway mediated downstream inflammatory response. HCV: Hepatitis C virus; ERS: Endoplasmic reticulum stress; AP-1: Activating protein-1; ASC: Apoptosis-associated speck-like protein containing CARD; DAMP: Damage associated molecular patterns; mtDNA: Mitochondrial DNA; MyD88: Myeloid differentiation factor 88; NLRP3: Nod-like receptor pyrin domain containing 3; ROS: Reactive oxygen species; vRNA: Viral RNA; TLR: Toll-like receptor; TNF-α: Tumor necrosis factor-α; IL: Interleukin.

Figure 2 Inflammatory cascade responses in the hepatic microenvironment. Crosstalk among parenchymal cells (hepatocytes), non-parenchymal liver cells (Kupffer cells and hepatic stellate cells) and recruited immune cells (macrophages, mast cells, dendritic cells and natural killer cells) plus hepatitis C virus replication in the hepatic microenvironment mediates inflammatory cascade signalling and exacerbates liver injury and disease progression. HSC: Hepatic stellate cells; NK: Natural killer; HCV: Hepatitis C virus.

Figure 3 Promising anti-inflammatory/hepatoprotective agents for chronic hepatitis C. HCV: Hepatitis C virus; IFN: Interferon; NS: Non-structural; HO-1: Heme oxygenase-1; TLR: Toll-like receptor.