TNF and cholestasis: This scenario is of particular relevance in some CLDs, such as in human ALD or experimental BDL [243,250]: both ethanol ingestion or experimental cholestasis can lead to significant translocation of gut derived endotoxins to the portal circulation, where they interact with the surface receptor CD14, resulting in activation of Kupffer cells and increased synthesis of pro-inflammatory cytokines (mainly TNF), eicosanoids, and, once again, ROS and NO.