Protection of cholangiocytes Bile, with its high concentration of hydrophobic bile salts, exhibits extracellular cytotoxicity in vitro, but does not cause cholangiocyte injury under physiological conditions. In PBC, inflammatory bile duct injury may be aggravated by hydrophobic bile salts. Two mechanisms have been discussed by which UDCA protects the biliary epithelium against toxic effects of bile, i.e., relative reduction of hydrophobic bile salts and enrichment of phospholipids in bile. When administered at recommended doses of 13 to 15 mg/kg/day, UDCA content may rise up to 50% of total bile salts [243] and to an even higher percentage when the dose of UDCA is increased [244, 245] . In consequence, bile composition is shifted towards less toxic and less hydrophobic bile salts.