title: Liver alkaline phosphatase: a missing link between choleresis and biliary inflammation.
abstract: Several lines of evidence show that serum alkaline phosphatase (AP) is not only a signpost of cholestasis but also a surrogate marker of the severity of primary biliary cirrhosis and primary sclerosing cholangitis. In the present opinion article, we review and discuss the putative role of liver AP in health and in cholestatic diseases. In inflammatory cholestatic conditions, loss of activity of liver AP (resulting from its relocation from canaliculi and the acidic milieu) might promote hyper-adenosine triphosphate-bilia, lipopolysaccharide overload, and subsequent exacerbation and perpetuation of inflammation. Drugs that can restore the polarity of hepatocytes and canalicular export of bile acids or act as bile alkalinity modifiers are predicted to exert anti-inflammatory effects and to benefit both primary biliary cirrhosis and primary sclerosing cholangitis. Oral administration of intestinal AP could be a valid therapeutic intervention that deserves further study under experimental conditions as well as in human diseases. Overall, the key role of the liver microenvironment that might shape the different facets of the inflammatory processes in fibrosing cholangiopathies is highlighted.
authors.affiliation: UPMC University of Paris 06, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Paris, France.|AP-HP, Hôpital Saint-Antoine, Service d'Hépatologie, Paris, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007239:Infections / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000201:enzymology*; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase