The pathophysiology of CFLD is not fully understood, but it is hypothesized that over time, impaired biliary secretion from abnormal cystic fibrosis transmembrane conductance regulator (CFTR) proteins in the apical membrane of cholangiocytes and the production of thick, viscous bile with increased free radicals leads to both direct hepatocyte damage and indirect periportal fibrosis as HSCs are activated to produce collagen [60]. Here, CFTR is linked to cystic fibrosis-related liver disease.