Bile Acids: From Genomics to Disease and Therapy

Since the last International Bile Acid Meeting in The Hague in 2000, bile acid research has continued to flourish and therapeutic use of bile acids has attained a broader role. Bile acid research has been stimulated by the discovery that bile acids specifically bind to receptors of the cell nucleus. Thereby, they regulate the transcription of transport proteins and enzymes involved in synthesis, transport and metabolism of bile acids and maintain cholesterol homeostasis. Knowledge about genetic defects of bile acid transport which may cause cholestasis or intestinal malabsorption has also increased impressively. Therapy of chronic cholestatic liver diseases, especially of primary biliary cirrhosis, with ursodeoxycholic acid represents an important advance in modern hepatology and has stimulated basic and clinical research to unravel the underlying mechanisms of action and to optimize treatment schedules.

This book is the proceedings of Falk Symposium 129, the XVII International Bile Acid Meeting held in Freiburg, Germany, May 30-June 1, 2002, which was again dedicated to both basic and clinical aspects of bile acid research with a focus on the role of bile acids in hepatobiliary and intestinal diseases. The latest findings are presented by the leading scientists and clinicians in the field.

List of Principal Contributors. Preface. Pathways and regulation of bile acid synthesis; J.B. Cheng, D.W. Russell. Section I: Regulation of Gene Expression by Bile Acids. 1. The homeostatic control of bile acid biosynthesis and transport by nuclear receptors; C.J. Sinal, F.J. Gonzales. 2. Coordinated regulation of hepatobiliary transporter genes by nuclear receptors; S. Karpen. 3. Transactivation of the human OATP8 gene by the Farnesoid X Receptor/Bile Acid Receptor (FXR/BAR); G.A. Kullak-Ublick, D. Jung. Section II: Synthesis and Metabolism of Bile Acids. 4. Vitamin D receptor as a bile acid sensor; T.T. Lu, et al. 5. Molecular mechanisms of nuclear receptor regulation of bile acid synthesis; J.Y.L. Chiang, et al. 6. Manipulating the bile acid pool regulates CYP7A1 by changing FXR activation; Guorong Xu, et al. Section III: Transport of Bile Acids and Bile Secretion. 9. Mutations in the sodium-independent bile salt uptake transporter of human liver SLC21A6; J. König, et al. 10. Regulation of the rat organic anion transporting polypeptide 4 (Oatp4) by bile acids; D.Rost, et al. 11. Regulation of expression and function of the canalicular bile acid export pump; P. Meier-Abt. 12. The in-vivo and in-vitro function of human BSEP; R. Thompson. 13. Sinusoidal efflux of bile acids; H.Akita, et al. 14. Organ-specific regulation of nuclear hormone receptors and bile salt transport proteins in obstructive cholestasis; A. Bohan, et al. Section IV: Bile Acids in Disease. 22. Acquired alterations of hepatobiliary transport systems in human cholestatic liver diseases: potential targets of pharmacotherapy; M. Trauner, et al. 23. Bilary lipid composition in BRIC patients; R.H.J. Houwen, et al. 24. Mutations in MDR3 in adult onset cholangiopathy; S. Strautnieks, et al. 25. MDR3 gene mutations and cholesterol cholelithiasis; O. Rosmorduc, et al. 26. Expression and localization of hepatobiliary transporters in primary biliary cirrhosis; H. Kojima, et al. 27. Neonatal liver disease in two siblings caused by a failure to racemize (25R)trihydroxy-cholestanoic acid due to a gene mutation in 2-methylacyl-CoA racemase: Effectiveness of cholic acid therapy in preventing liver and neurological disease; K.D.R. Setchell, et al. Section V: Bile Acids in Therapy. 28. UDCA and TUDCA ameliorate hepatocyte damage caused by EtOH and acetaldehyde by different mechanisms; U. Leuschner, et al. 29. Ursodeoxycholic acid therapy affects the cytokine network and plays an immunomodulatory role in patients with primary sclerosing cholangitis and primary biliary cirrhosis; M.G. Neumann, et al. 30. Dose response of UDCA in the treatment of cholestatic disorders; G. Mazzella, et al. 31. High dose ursodeoxycholic acid in the management of primary sclerosing cholangitis; R.W. Chapman. 32. Intrahepatic cholestasis of pregnancy: a placebo controlled randomised trial of ursodeoxycholic acid vs. dexamethasone on maternal and fetal outcome and metabolism; A Glantz, et al. 33. Ursodeoxycholic acid in the chemoprevention of colon cancer; K. Kowdley. Index. Ten Additional Articles.