The pathogenesis of cell death and necrosis in the liver is a central topic of research in liver disease. A molecular understanding of events and sequences leading to cellular death provides the basis for preventive and therapeutic efforts. This volume originates from a "Workshop on Experimental Liver Injury" held on November 9 and 10, 1974, in Freiburg, Germany. Recent progress in the elucidation of the mode of action includes agents inducing liver cell necrosis by a primary dis- turbance of nucleotide and nucleic acid metabolism as well as hepa- totoxins characterized by a primary attack on cellular membranes. I hope that this book will contribute to an increasing understanding of disease mechanisms. Freiburg im Breisgau Dietrich Keppler June 1975 Acknowledgments The generous support from Dr. H. Falk, Freiburg, has been a prereqUIsite for the organisation and publication of the meeting on "Pathogenesis and Mechanisms of Liver Cell Necrosis". I wish to express my sincere thanks for this sponsorship. I am indebted to those who acted as chairmen during the meeting: Professors H. Remmer (Tilbingen), M. Frimmer (Giessen), W. Gerok (Freiburg), H. Popper (New York), H. Schimassek (Heidelberg), and K. Decker (Freiburg).

Beginning in 1970, the International Bile Acid Meeting has taken place every two years and each time new progress in our understanding of the complex role of bile acids in many metabolic processes of the liver and the intestine has been revealed by a selected group of leading scientists from all over the world. Although originally mainly physiological data on bile acid synthesis and transport were emphasized, and later on also the therapeutic benefit of bile acids in gallstone disease and cholestasis was discovered, we have come now to the molecular biology and genetic era with major discoveries in transport defects and related diseases. This book is the proceedings of Falk Symposium No. 120, held in The Hague, The Netherlands, on October 12-13, 2000 - the 16th International Bile Acid Meeting. One of the main discoveries recently has been the identification of nuclear receptors for bile acids, which gives them a much broader perspective than previously anticipated. It even suggests that bile acids can regulate their biosynthesis and enterohepatic circulation transcriptionally. It will therefore not be surprising that this topic, together with the molecular regulation of cholesterol 7alpha-hydroxylase and cholesterol homeostasis, has a dominant place in these proceedings. Another important topic is the progress in our molecular understanding of hepatic (both at the basolateral and canalicular sites), cholangiocytic and intestinal bile acid transport processes. Further insights into genetic defects causing cholestasis or intestinal malabsorption in animal models and in human diseases are also discussed by a number of well-known authors. Finally the last section deals with new findings on the role of bile acid therapy in cholestatic syndromes or chemoprevention and with the potential benefit of bile acid inhibitors. All contributors provide an update on the most recent developments in their field.

There has been a tremendous amount of scientific progress in our understanding of the molecular mechanisms of transport processes in the liver within the last few years. Cloning of various members of organic anion and cation transporters has provided the necessary tools to study their regulation under physiological and pathophysiological conditions and has advanced our knowledge about bile formation. Mutations of various hepatic organic anion transporters have been identified in humans as hereditary defects leading to the heterogenous syndrome of progressive familial intrahepatic cholestasis (PFIC). Various mouse models including knockout animals have given us the opportunity to gain insight into lipid transport by the liver and the genetics of cholesterol gallstone formation. The physiology of bile duct cells and the molecular mechanisms leading to various cholangiopathies have been a main scientific focus in hepatology in recent years. Drug targeting to the liver by hepatic organic anion transporters represents an attractive way of selective delivery of pharmaceutical agents in humans. Ursodeoxycholic acid is successfully used in the treatment of patients with chronic cholestatic liver disease and major advances have been made in understanding its mode of action in liver and bile duct cells. This book, the proceedings of the Falk Workshop held in Aachen, Germany, on 25-26 January 2001, contains chapters on all important aspects of biliary transport by well-known experts in this field. It is an essential resource for new developments in the field of biliary transport, both in basic science and clinical medicine.

Since the last International Bile Acid Meeting in Stockholm in 2004, bile acid research has continued to flourish and therapeutic use of bile acids has attained a broader role. New insights have been gained into the mechanisms responsible for maintenance of bile acid homeostasis, and effects of bile acids on the cell signalling pathways have been further elucidated. Knowledge of the genetic basis of bile acid physiology has further increased. Therapy of chronic cholestatic liver diseases with ursodeoxycholic acid and new aspects of its chemopreventive properties continue to stimulate basic and clinical research and contribute to the understanding of underlying modes of action and to optimized treatment schedules. Chapters reflect the recent progress in bile acid metabolism and transport, nuclear receptor regulation and signaling by bile acids, as well as mechanisms of bile acid-induced cellular injury...

Since the last International Bile Acid Meeting in Freiburg in 1996, considerable progress has been made in several areas of bile acid research. The different pathways of bile acid synthesis and their regulation have been further characterized. The molecular mechanisms for biliary secretion of bile acids have been elucidated and genetic defects of bile acid transport have been defined. Injurious as well as protective effects of different bile acids on the liver have been further studied. Finally, the beneficial effects of ursodeoxycholic acid in cholestatic liver diseases have been substantiated and the potential mechanisms of action have been explored. This book, the proceedings of the Falk Symposium No. 108 (XV International Bile Acid Meeting), held in Titisee, Germany, October 12-13, 1998, is dedicated to both basic and clinical aspects of bile acid research with a focus on bile acids and cholestasis.

This book is the proceedings of the 18th International Bile Acid Meeting, held as the Falk Symposium 141 in Stockholm, Sweden, on June 18-19, 2004. The International Bile Acid Meetings have become some of the most important meetings in the bile acid field worldwide since Herbert Falk decided to sponsor these Symposia in biannual sequence in 1970. The 17 International Bile Acid Meetings in the past have been a great stimulus for new ideas and methods as well as the development of therapeutic applications of bile acids. They have always been a forum where basic scientists and clinicians interact. Many novel results of bile acid research were first presented at these meetings. The meeting in Stockholm again attracted a large number of basic and clinical scientists interested in bile acid and biliary research from all over the world. Knowledge about the regulation of bile acid synthesis, bile acid transport and enterohepatic circulation in health and in disease has increased considerably during recent years. Accordingly, bile acid research is alive as ever. A new chapter of bile acid research was opened by the finding that bile acids are ligands of nuclear receptors which regulate synthesis, metabolism and transport of bile acids and steroids. A large part of the book is devoted to these topics. The 18th International Bile Acid Meeting was again a truly interdisciplinary symposium at the highest scientific level. Its participants enjoyed hearing the latest reports on bile acid research in the city where so many seminal studies on bile acids were performed. It is hoped that the readers of this book will share the enjoyment.