CFTR and cystic fibrosis: Within the monogenic diseases with both intrahepatic and extrahepatic manifestations, cystic fibrosis (CF) was the first human monogenic disease modelled with organoids, specifically using human intestinal organoids derived from rectal biopsies of patients with CF.79 The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a chloride channel normally expressed in epithelial cells of many organs, including on the surface of cholangiocytes and bile duct cells.