Fig. 2.

Effects of bile acid accumulation in the liver. Bile acid accumulation in cholestatic conditions can activate different signaling pathways in different cell types of the liver. Damaged hepatocytes can initiate an inflammatory response by secreting chemokines and DAMPs that activate other cells (i.e., cholangiocytes, HSCs, and inflammatory cells). High levels of bile acids can also directly disrupt tight junctions and basal membrane of bile ducts, leading to activation of cholangiocytes and perpetuation of the inflammatory/fibrotic response with proliferation and activation of HSCs. Persistent chronic inflammation and fibrosis can progress into cirrhosis. DAMPs: damage-associated molecular patterns; HSCs: hepatic stellate cells; lncRNA H19: long non-coding RNA H19