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In recent years, our knowledge about the pathogenesis,
pathophysiology and treatment of hepatobiliary diseases has
increased considerably. The molecular basis of cholestatic
disorders as well as of gallstone disease is increasingly
recognized. This has resulted in improved diagnosis, for instance
in hereditary forms of intrahepatic cholestasis, and advances in
treatment, for example in primary biliary cirrhosis and other
chronic cholestatic disorders. This book, the proceedings of a Falk
Workshop held in Cluj-Napoca, Romania, on June 9-10, 2000, brings
together contributions from scientists and clinicians to highlight
the most recent advances in molecular biology, pathophysiology,
diagnosis and therapy of diseases of the hepatobiliary system.
World experts cover a broad spectrum of topics from genetic studies
to endoscopy and from medical treatment to liver transplantation.
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 contains the proceedings of the XIIIth International Bile
Acid Meeting (Falk Symposium 80), an official satellite meeting of
the World Congress of Gastroenterology, held in San Diego,
California, U.S.A., September 30--October 2, 1994. It begins with
presentations of major advances in bile acid chemistry, biology and
pharmacology. The new structure proposed for the mixed micelles
present in bile is reviewed, as are the properties of new synthetic
analogues of bile acids. The mechanisms by which bile acids
interact with cell membranes are discussed in order to provide
insight into the hepatotoxic effects of bile acids in cholestatic
liver disease. The book further shows the exciting progress in the
molecular biology of bile acid transport by the hepatocyte and
enterocyte, and concludes with a consensus on the use of
ursodeoxycholic acid in cholestatic liver disease and as an adjunct
to immunosuppressive therapy after liver transplantation, and to
interferon therapy in chronic viral hepatitis.
In recent years, knowledge about the cell biology of the
cholangiocytes and the function of the bile ducts has increased
considerably. Their role in liver diseases is increasingly
recognized. As a consequence, important progress has been made not
only in the pathogenesis and pathophysiology but also in the
diagnosis and treatment of biliary liver diseases. This book, the
proceedings of the Falk Symposium 107 on Diseases of the Liver and
the Bile Ducts - New Aspects and Clinical Implications', held in
Prague, Czech Republic, on April 30-May 2, 1998, brings together
scientists and clinicians to highlight the most recent advances in
molecular biology, physiology, diagnosis and therapy of diseases of
the biliary system. World experts cover a broad spectrum of topics
from genetic tests to endoscopy and from medical treatment to liver
transplantation.
Bile acid research has attracted increasing attention from both
basic scientists and clinical hepatologists over the last decade.
Experimental studies have expanded our knowledge of the role of
bile acids in liver disease, and well-designed clinical trials have
documented beneficial effects of bile acid treatment for a number
of hepatobiliary diseases. Bile Acids in Liver Diseases, the
proceedings of an International Falk Workshop held in Munich,
January 1995, provides insights into current concepts in bile acid
chemistry, bile acid synthesis and metabolism, and transport of
bile acids across the hepatocyte. The role of bile acids in bile
formation, cholestasis and hepatotoxicity are discussed. Finally,
the book addresses experimental studies and hypotheses about the
putative mechanisms of action of ursodeoxycholic acid in
cholestatic liver diseases, and summarizes the clinical
applications of bile acid treatment on the basis of controlled
clinical trials.
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. Now, 7 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 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. Recently the International
Autoimmune Hepatitis Group newly defined and reclassified the
syndrome of autoimmune hepatitis. Autoimmune hepatitis is now
identified and studied in all parts of the world, including Asia
and South America. A special variant of autoimmune hepatitis was
identified as one organ manifestation of the autoimmune
polyendocrine syndrome type 1, a genetic disease caused by
mutations in a single transcription factor. 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 characterisation
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. Liver transplantation is the
treatment of choice for end stage liver diseases; all autoimmune
liver diseases are among the best candidates for liver
transplantation. Hopefully, new therapeutic strategies based on the
results obtained from experimental models will become everyday
clinical practice in the next decade. Therefore this symposium
concludes with a discussion.
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...
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. Now, 7 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 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. Recently the International
Autoimmune Hepatitis Group newly defined and reclassified the
syndrome of autoimmune hepatitis. Autoimmune hepatitis is now
identified and studied in all parts of the world, including Asia
and South America. A special variant of autoimmune hepatitis was
identified as one organ manifestation of the autoimmune
polyendocrine syndrome type 1, a genetic disease caused by
mutations in a single transcription factor. 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 characterisation
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. Liver transplantation is the
treatment of choice for end stage liver diseases; all autoimmune
liver diseases are among the best candidates for liver
transplantation. Hopefully, new therapeutic strategies based on the
results obtained from experimental models will become everyday
clinical practice in the next decade. Therefore this symposium
concludes with a discussion.
Die gro~en Fortschritte in der Hepatitisforschung, die zur
Entdeckung und Charakterisierung von 5 unterschiedlichen
Virushepatitiden f}hrte, erbrachteneue Erkenntnisse f}r die
Epidemiologie, Infektiosit{t und zur Pathogenese. Es gelang die
Entwicklung eines wirksamen und sicheren Impfstoffs gegen die
Virus-B-Hepatitis. Dagegen ist die Therapie der akuten
Virushepatitis und chronischen Virus-B, -C- und -D-Hepatitis noch
unbefriedigend. Mit der Einf}hrung von Interferon alfa in die
Behandlung der chronischen Virushepatitiden haben sich neue
therapeutische Ans{tze ergeben, obwohl erst ungef{hr 30-40% der
Patienten davon profitieren. Eine Anzahl von sorgf{ltig
durchgef}hrten kontrollierten Therapiestudien im In- und Ausland
haben inzwischen zu }bereinstimmenden Therapieempfehlungen gef}hrt,
die in diesem Buch wiedergegeben werden. In diesem Buch werden die
Epidemiologie, Pathogenese, Klinik und therapie sowie die Prognose
der chronischen Virushepatitiden einschlie~lich der Nebenwirkung
ausf}hrlich beschrieben. Es wendet sich daher an alle [rzte, die
gegenw{rtig oder in Zukunft Patienten mit chronischer
Virushepatitisbehandeln.
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.
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