In a recent review, Trauner et al. list the various causes for “toxic” bile formation, among them an increased bile acid/phospholipid ratio, as is the case in patients with MDR3 mutations or the mdr2−/− mouse, or a decreased HCO3− concentration and bile hydration, such as in cystic fibrosis patients and in the cftr−/− mouse, or possibly due to AE2 downregulation in primary biliary cirrchosis [50]. This evidence concerns the gene ABCB4 and cystic fibrosis.