PMC

Diseases of civilization are usually a cause or consequence of liver and gall bladder diseases

3D hepatic organoid by Daniel Mueller and Patrina Gunness; fluorescence image taken at the Karolinska Institute, Stockholm, Sweden.

PPARα, peroxisome proliferator‐activated receptor α. SHP, small heterodimer partner; UGT, uridine 5'‐diphospo‐glucuronosyltransferase; SULTs, sulfotransferases.

NAFLD, non‐alcoholic fatty liver disease; NASH, non‐alcoholic steatohepatitis; ALT, alanine transaminase; AST, aspartate transaminase; γ‐GT‐gamma glutamyl transferase. An up arrow indicates increase and down arrow indicates decrease.

After bile acid (BA) synthesis in hepatocytes, BAs are mono‐conjugated and are excreted through the bile salt export pump (BSEP) into the bile canaliculi. The divalent BAs are excreted by the multidrug resistance‐associated protein 2 (MRP2) and the multidrug export pump (MDR). These bile acids are secreted as bile into the ileum where they may be further conjugated and metabolized. BAs are then recycled into the liver via the portal vein, being taken up mainly by the Na⁺–taurocholate co‐transporting polypeptide (NTCP) and to a lesser extent by the organic anion transporter proteins (OATP1 and OATP4). During bile acid overload or cholestasis, BAs can be secreted into the systemic circulation through MRP3 and MRP4 and also to some extent via OATP2 and OST‐α and ‐β. Figure adapted from Thomas et al. () with permission from Macmillan Publishers Ltd.