Specifically, the ADAM17-mediated enhanced release of proinflammatory cytokines within the liver microenvironment, such as cleaving soluble TNFα from the cell surface of infiltrating or resident hepatic immune cell populations (44), likely significantly contributes to liver injury and has been implicated in the pathogenesis of both PBC and PSC (19, 21, 61, 62). This evidence concerns the gene TNF and primary biliary cholangitis.