U. Leuschner - Böcker

Pregnancy is the main determinant of some liver diseases in humans: acute fatty liver of pregnancy, cholestasis of pregnancy, and acute liver failure in toxaemia of pregnancy. Pregnancy also modifies the natural history of other more common hepatobiliary diseases, such as cholesterol gallstones. Sex hormones (mainly oestrogens, progesterone and/or some of its metabolites) and prolactin are considered responsible for these pathological consequences and they also appear to be influential in the outcome of several other hepatobiliary disorders, in both sexes and all ages. Although these disorders and their hormonal interrelations have been clinically well characterized, their pathogenesis remains obscure from the biomolecular point of view. In recent years, novel approaches using new technologies have improved our understanding of hormone actions and metabolism, hormone receptors, metabolic pathways and their interrelations with closely related molecules, such as bile acids. This book, the proceedings of the 89th Falk Symposium, held in Santiago, Chile, 10-11 November, 1995, will help research scientists and clinicians to review basic and clinical aspects of these interactions, in order to stimulate biomedical research in a relevant and exciting area.

In 1992, the Falk Symposium No. 70 dealt with the topic "Immunology and Liver". At that time, basic mechanisms of immunology as well as immunopathogenetic mechanisms in viral and autoimmune liver diseases were discussed. Seven years later, the Falk Symposium No. 114, held in Basel, Switzerland, October 20-21 1999 (Part I of the Basel Liver Week 1999), focused on immunology in autoimmune liver diseases. In the first section of this text, basic mechanisms of autoimmunity are presented, including the relevance of superantigens and the role of apoptosis. A further topic is the latest developments concerning animal models for autoimmune diseases. Drug- and hepatitis-virus induced immune mediated liver diseases may serve as models for nonhepatic immune mediated disorders. DNA technology has increased our knowledge of the immunogenetic background of autoimmune liver diseases. Among the cholestatic immune mediated liver diseases, significant progress has been made concerning primary biliary cirrhosis, in particular regarding the identification of mitochondrial antigens and the characterization of the immune reactions directed at them.The involvement of infectious agents in PBC as well as the definition of overlap syndromes is a particular focus for basic and clinical research in this area. Concerning the therapy of autoimmune liver diseases, corticosteroids and azathioprin remain the state of the art for autoimmune hepatitis, while bile acids have become well established in treatment of primary biliary cirrhosis as well as primary sclerosing cholangitis. New drugs in the future will include topical steroids such as budesonide and new immunosuppressive agents like mofetil/mycophenolate.

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.

This book is the proceedings of the Falk Symposium No. 121 on "Steatohepatitis (NASH and ASH)", held in Den Haag, The Netherlands, on October 14-15, 2000. The histological features of what we now call non-alcoholic steatohepatitis were described as early as 1962, and in 1980 the name "non-alcoholic steatohepatitis" or NASH was applied. The same year, NASH was recognized as one of the most common liver diseases in Western countries when viral hepatitis and heavy alcohol consumption were excluded. ASH, or alcoholic steatohepatitis, is more common than NASH, since alcohol is omnipresent in Western as well as Eastern cultures. Histologically NASH and ASH are similar or even identical. Morphological findings range from fatty degeneration to inflammation and fibrosis, and may end up in liver cirrhosis. In spite of the well-defined morphological features, knowledge of epidemiology, aetiology, and pathogenesis contains gaps, especially for NASH. Therefore, it is the purpose of this book to show the state of the art, to discuss scientific data, and to suggest possible treatment strategies, hoping to stimulate clinicians as well as scientists.

Since the 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 most up-to-date findings are presented by leading scientists and clinicians in the field.

During the last decade, knowledge about cholestatic liver disease and concomitant diseases, such as ulcerative colitis, cholangio- and hepatocellular carcinoma, pancreas and colon cancer, has increased considerably.

This book reflects 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. Coverage examines bile acids as therapeutic agents, particularly for the treatment of cholestatic liver diseases. This volume in the Falk Symposium series brings together basic science and clinical hepatology in the field of bile acids.

Leber- und Gallekrankenheiten nehmen in Klinik und Praxis einen zentralen Platz ein. Deshalb ist die Kenntnis der neuesten Therapie-Fortschritte auf diesem Gebiet für Internisten unverzichtbar. Das erfolgreiche Therapie-Handbuch bietet eine ideale Orientierungshilfe: kompakt, praxisbezogen, mit gesicherten Therapie-Empfehlungen und genauen Therapie-Anwendungen. Die Neuauflage ist komplett überarbeitet und um neueste Erkenntnisse zur Interferon-Therapie, zur Behandlung der Hepatitiden sowie um die Ständigen Empfehlungen der Impfkommission (STIKO) erweitert.