“…-Facilitates viral particle binding in both HBV and HCV (189,190) LMW-HA TLR2, TLR4, CD44 (119,120,122,(191)(192)(193) Direct Ligand: Immune cell interactions -Generated during inflammation and tissue injury by endogenous and bacterial hyaluronidases and by mechanical forces and oxidative stress (194,195) -Activates pro-inflammatory response in macrophages (119,121,122), dendritic cells via TLR4 and endothelial cells (191) -Stimulates macrophages to produce IL-8, IL-12, MIP-1a, MIP-1b, and MCP-1 (119,121,122) -Stimulates DCs and endothelial cells to produce IL-1b, TNF-a, and IL-12 (191) ECM-DAMP -LMW-HA is considered an ECM-DAMP known to activate the inflammasome and subsequently caspase-1 (126). The activation of the -Hyaluronic acid is upregulated in liver connective tissue of patients with steatosis, steatohepatitis, cirrhosis, and HCC (197) (Continued) and HSCs, HBV core protein was able to induce expression of TSP-1 by hepatic cells and induce activation of TGF-b1 (294).…”