With a focus on practical patient related issues, Autoimmune Hepatitis: A Guide for Practicing Clinicians serves as a useful practical, and much needed, resource for all those physicians presented with managing patients diagnosed with autoimmune hepatitis, both acutely and over the long term. It provides a basis for clinicians to understand the etiology of the disease, as well as special circumstances where management dilemmas often arise. Emphasis is given to providing management advice of immediate use to clinicians, something not presently offered by other larger general texts. The chapters are written by those with an expertise and training in this field and include the most up to date information. The book will be of great value to Gastroenterologists, Hepatologists, and Internists at all levels who see patients presenting with autoimmune hepatitis.

This book is the proceedings of the Falk Symposium No. 137 on "Liver Diseases: Advances in Treatment and Prevention" (part of the XII International Falk Liver Week 2003 in honour of Hans Poppera (TM)s 100th birthday, held on October 17-19, 2003). It covers our present knowledge of the diagnosis, treatment and prevention of liver diseases, including hepatitis B, hepatitis C and delta hepatitis as well as alcoholic liver diseases, non-alcoholic steatohepatitis and the hereditary liver diseases haemochromatosis, Wilsona (TM)s disease and alpha-1-antitrypsin deficiency. In addition to these clinical entities, the sequelae of liver cirrhosis and its complications, including the clinical management of ascites, the hepatorenal as well as the hepato- and porto-pulmonary hypertension syndrome are discussed. New developments with respect to liver support systems and liver transplantation are further highlights of the proceedings.

The main topics mentioned above are complemented by state-of-the-art chapters on "Hepatocellular Carcinoma," "Emerging Hepatitis Viruses" and "Fulminant Liver Failure" that are of interest to both basic scientists as well as clinicians. A special section is devoted to "Liver Histology" as a tribute to Hans Popper who contributed eminently to the basic and clinical aspects of hepatology.

All in all, Liver Diseases: Advances in Treatment and Prevention provides an exciting overview of the current developments in the treatment and prevention of viral, alcoholic, non-alcoholic and hereditary liver diseases, presented by an international faculty of outstanding scientists and clinicians.

In several liver diseases, the underlying cause cannot always be eliminated, i.e. the progression of liver disease cannot be prevented. This is particularly true for non-responders to the treatment of chronic hepatitis C (HCV). It is relevant for more than 40 per cent of patients with HCV genotype 1 and up to 20 per cent of patients with genotype 2 or 3. Several approaches are now underway to prevent or ameliorate mechanisms of disease progression. In Asia, and particularly in Japan, Glycyrrhizine-SNMC has been widely used for this purpose. At present, SNMC is under clinical evaluation in Europe.

Primary Liver Cancer: Surveillance, Diagnosis and Treatment focuses on the many therapies rapidly evolving to assist with controlling hepatocellular carcinoma as well as emerging technologies to assist in early diagnosis as well as prevention. All chapters are written by experts in their fields and include the most up to date information for diagnosis, treatment, surveillance, epidemiology, staging, recurrence and prevention. This volume will serve as a useful resource for clinical gastroenterologists, hepatologists, oncologists, pathologists, and physicians who treat patients with chronic liver disease and hepatocellular carcinoma.

Malignant neoplasms occurring in the biliary tract and pancreas remain a therap- tic challenge. The mechanism of carcinogenesis as well as the growth and spread of these tumors is still poorly understood, making the development of rational tre- ment strategies difficult. In order to improve the clinical results achieved by sur- cal or other medical treatment of such malignant tumors, the establishment of an experimental animal model is critical. For this purpose, attempts were made to induce carcinoma experimentally in the biliary tree and finally an animal model using the hamster was established in 1994 at our laboratory. Because the tumor in this model mimicked the characteristics of human tumors, a series of experimental investigations were conducted to clarify the pathological characteristics of biliary carcinoma, the genetic alterations during biliary carcinogenesis, and the relationship between biliary inflammation and c- cinogenesis. The chemopreventive effects on the occurrence of biliary carcinoma were also successfully examined. In addition, in vitro studies led to the establi- ment of transplantable biliary cancer cell lines and biliary epithelial cell lines by utilizing the hamster model. This monograph represents the collective efforts in hepato-biliary and pancreatic disease research over the past 20 years. I hope that this monograph will be a source of useful knowledge for basic researchers as well as for clinicians involved in the care of patients with hepato-biliary and pancreatic neoplasms. Takashi Kanematsu, M.D., Ph.D.

This book, the proceedings of a Falk Workshop on `Topical Steroids in Gastroenterology and Hepatology', held in Berlin, Germany, on 14 June 2003, critically discusses the current role of budesonide in gastroenterology, hepatology, surgery and oncology and focuses especially on potential new indications for the use of budesonide. A number of smaller clinical studies and anecdotal case reports with impressive clinical effects are reported in patients with gastrointestinal, hepatic, oncological and surgical problems. In addition, the use of budesonide for the treatment of distal ulcerative colitis and ileocolonic Crohn's disease is evaluated with respect to its role in an evidence-based management of IBD. Finally, as clinical experience with the use of budesonide is increasing, safety issues and the side-effect profile of budesonide is addressed.

Despite numerous hepatitis C virus infection studies, its pathogenesis and medical treatment have not been fully explained. This comprehensive volume, written by experts in the field, covers the most recent advances in the study of HCV, moving from basic research to clinical applications. The first chapters of this volume analyze the full spectrum of immune responses to HCV. The volume also includes contributions that explain the state of the art in IFN-alpha treatment of HCV patients.

Chronic liver failure is a frequent condition in clinical practice that encompasses all manifestations of patients with end-stage liver diseases. Chronic liver failure is a multiorgan syndrome that affects the liver, kidneys, brain, heart, lungs, adrenal glands, and vascular, coagulation, and immune systems. Chronic Liver Failure: Mechanisms and Management covers for the first time all aspects of chronic liver failure in a single book, from pathogenesis to current management. Each chapter is written by a worldwide known expert in their area and all provide the latest state-of-the-art knowledge. This volume is specifically designed to provide answers to clinical questions to all doctors dealing with patients with liver diseases, not only clinical gastroenterologists and hepatologists, but also to internists, nephrologists, intensive care physicians, and transplant surgeons.

Cell-cell and cell-matrix interactions are of fundamental importance for the development and the maintenance of tissues and organs in multicellular organisms. Adhesive processes are mediated and controlled by an increasingly large and complex number of cell adhesion molecules that are anchored to the cell surface membrane by transmembrane domains. According to their structural and functional features, cell adhesion molecules have been classified into at least four major families: the integrins, selectins, cadherins and members of the immunoglobulin superfamily. Apart from linking cells to each other or to components of the extracellular matrix, cell adhesion molecules function also as receptors that interact via their cytoplasmic domain with numerous signalling molecules including protein kinases and phosphatases, G-proteins, or proteins of the beta-catenin/armadillo family. Cell adhesion molecules can activate various signalling pathways and as a consequence play a crucial role in the regulation of cell differentiation, proliferation, migration and apoptosis. During the last decade it has been recognized that acquired as well as inherited defects of cell adhesion molecules and adhesion-linked signalling molecules are the molecular basis of various types of disease including cancer, infectious and inflammatory disease, connective tissue disorders or blistering disease.
This book is the proceedings of a Falk Workshop held in Berlin, Germany, on January 23-24, 2003, which brought together experts in different fields of research to stimulate the transfer of findings from basic research to clinical application. Section I focuses on cell adhesion molecules of the liver and their role inhepatocarcinogenesis and inflammatory liver disease. Section II deals with infection and fibrosis and with transforming growth factor beta (TGF-beta). Morphogenesis, cell migration and inflammation are the subject of Section III with a focus on the role of integrins in blood cell-endothelial interactions. In Section IV the importance of cell adhesion molecules for cancer and their role as potential target for cancer therapy will be discussed.

The rise in hepatocellular carcinoma (HCC) mortality rates has caused researchers to focus increased attention on liver cirrhosis, a pathological condition known to lead to HCC. If hepatic fibrosis can be controlled, it follows that the risk of HCC among patients with chronic hepatitis can be reduced. In the quest for greater understanding of liver cirrhosis, the 1999 Yamaguchi Symposium on Liver Diseases brought together leading researchers in the field. Guest speakers included Michael J.P. Arthur, on mechanisms of the progression and regression of liver fibrosis; Mark A. Zern, on novel therapeutic modalities for hepatic disease; and Jiro Fujimoto, on gene therapy to inhibit progression to liver cirrhosis. The presentations by these groundbreaking scientists are collected in this volume along with those of other leading researchers in the field of hepatology, creating a valuable source for professionals concerned with hepatic fibrogenesis and hepatocarcinogenesis.

My training started in 1971, when I joined the First Department of Medicine of Chiba University, as Dr. Kunio Okuda became chair ofthe department. To acquire training ingeneralpathology, Iapplied for the Intern MatchingProgram and started as aninternin the DepartmentofPathologyofYale University, in 1973.While Iwas achiefresident, Ispent 10months in Dr. GeraldKlatskin'sofficestudyingthe com plete set of his famous liver biopsy samples (the Klatskin Collection). In 1976, I movedtoJohnWesleyHospital, where therewasagroup from the USC (University ofSouthern California) Liver Unit, to obtain further pathology training under the guidanceofDr. Robert L. Peters. Those experiences have given me ample opportu nity to see the differences between the United States and Japan. Ofcourse, 28 years ago in downtown Los Angeles there were enormous num bers ofpatients suffering from typical alcoholic liver diseases. Now in Japan, in contrast, we have an enormous number ofpatients suffering from hepatocellular carcinoma (HCC), due in particular to hepatitis C viral infection. Last year, in the DepartmentofGastroenterology at the University ofTokyo, we had approximately 500 admissions due to HCC. Thus, we have an urgent need to prevent the develop ment ofHCC and to provide better treatment for such patients through a basic un derstanding ofvirology, clinical features, and treatment modalities. The first single-topic conference on "TherapyofViral Hepatitis and Prevention ofHepatocellular Carcinoma" was organized by the Japan Society ofHepatology (Kiwamu Okita, Director General) and was held November 14-15,2002, near Mt. Fuji. Thisbook, which is asummaryofthe meeting, helps toupdate relevantinforma tion on this vital topic. June 28, 2003 Masao Ornata, M.D."

The application of molecular techniques to gastroenterology continues to yield important advances in the development of drugs to treat gastrointestinal disorders. Important new drugs have emerged through the collaborative and complementary efforts of basic scientists, clinicians, and clinical researchers in academia and the pharmaceutical industry. The challenge has been exciting, with a few surprises along the way. Consider peptic ulcer disease as an example. The discovery of H receptors and the availability of potent and 2 selective H-receptor antagonists signaled the beginning of a new era 2 in the treatment of gastric hypersecretory states and peptic ulcers. Introduction of proton pump inhibitors offered another therapeutic option. Though H-receptor antagonists and proton pump inhibitors 2 are important and useful drugs, the discovery of the link between H. pylori infection and peptic ulcer disease has led to even more effective pharmacotherapeutic regimens. Our intent in Drug Development: Molecular Targets for GI Diseases is to bring together hands-on experts to review promising areas of gastrointestinal pharmacology. The contemporary topics covered, from a mechanistic viewpoint, are relevant to gastrointestinal inflammation and motility disorders. Authoritative opinions are offered on both future research directions and potential applications for new therapies.

This volume examines the current state of free radical biology as it impacts on hepatic disorders. It takes a thorough look at the relationship of oxidative stress in acute and chronic disease and takes into account factors like: redox biomarkers; antioxidant defense and protection; cell signaling, mutations; oxidative damage involving lipids, proteins and nucleic acids; membrane trafficking, inflammation, mitochondrial dysfunction, alterations in immunological function and toxicology and hypoxia. Studies on Hepatic Disorders, the latest volume in the Oxidative Stress in Basic Research and Clinical Practice series, provides a comprehensive look at liver topics. It is organized into four sections, each one thoroughly covering its topic and consisting of chapters written by recognized field leaders. Section One, covers basic principles including redox signaling, antioxidant defenses, nitric oxide, oxidative mechanisms in senescence and regeneration and the detection of oxidative stress. Section Two, explores Pathophysiology. It ranges from cell damage to fibrogenic response as broken out in chapters on hepatocellular injury, mitochondrial damage, unfolded protein response and autophagy, inflammation, ischemia-reperfusion injury and finally, fibrogenesis. Sections Three and Four cover specific diseases and cancer, respectively. Most of the chapters focus on diseases including acute failure, alcoholic disease, viral hepatitis, iron overload, autoimmune disease, Wilson's disease and more, while the chapters on cancer round out the book.

This book, the proceedings of Falk Symposium No. 125 on 'Cytokines in Liver Injury and Repair' (Progress in Gastroenterology and Hepatology Part II), held in Hannover, Germany, on September 30 - October 1, 2001, provides an update of our current knowledge on the role of cytokines in various human and experimental liver diseases and on their present and prospective use in therapeutic trials.

Developments in recent years include: Since the first report of a cytokine knockout mouse for IL-2 in 1991 a large number of cytokine and cytokine receptor genes have been inactivated in mouse germlines and the corresponding mutant mice have provided a wealth of novel information. In addition, targeted-gene disruption techniques (e.g. cre-loxP) and liver-specific overexpression of certain cytokines have provided clues for the understanding of their role in the pathophysiology of liver diseases.

The number of well-characterized cytokines, chemokines, and growth factors is ever growing and it becomes increasingly evident that they are effective in a complex network of positive and negative signals. A disruption of this homeostatic balance is a direct cause of disease, determines its complications, and is related to its progression, e.g. in inflammation and fibrogenesis.

Signaling pathways from receptors to target genes have been dissected and now we are beginning to recognize highly complicated cross-talks between various signal transduction pathways and interferences with non-cytokine mediators such as reactive oxygen metabolites (ROS), lipid mediators, physical factors, and others leading to an almost incomprehensible vastness of agonistic and antagonistic signals.

Today, we understand in greater detail the extracellular control mechanisms of cytokine and growth factor bioavailability and its importance for pathophysiological mechanisms. During these processes the secretion of (latent) proforms of cytokines, their extracellular or transmembraneous immobilization and sustained proteolytic activation and their release into the immediate environment of cells play major roles and the possibility of autocrine, paracrine, juxtacrine, and endocrine signal transfer.

Finally, experimental and beginning clinical uses of proteins or gene transfer technologies for cytokine antagonism, scavenging, receptor blockade, and inhibition of signal cascades in therapeutic trials offer hopeful perspectives in the treatment of malign and benign liver diseases. Gene-therapeutic application of molecular-engineered 'designer cytokines', e.g. of hyper-IL-6, promises clinical benefit for the treatment of fulminant hepatic failure.

The book contains chapters by most well-known experts in the field who have contributed significantly to our present knowledge on cytokines in liver injury and repair.

Hepatitis viruses research started more than fifty years ago. The names of hepatitis A and hepatitis B were introduced in 1947 when it became clear that there were two types of hepatitis that were transmitted either enterically or parenterally. It became apparent in the 1970's that there were additional hepatitis viruses distinct from hepatitis A and hepatitis B, and thus, the term non-A, non-B hepatitis was introduced. The non-A, non-B hepatitis was further divided into post-transfusion non-A, non-B hepatitis and enterically-transmitted non-A, non-B hepatitis in the 1980's. By the end of the 1980's, both post-transfusion non-A, non-B virus and enterically-transmitted non-A, non-B virus had been identified and renamed hepatitis C virus and hepatitis E virus, respectively. Hepatitis delta antigen was first recognized as an antigen associated with hepatitis B virus infection in the 1970's. In the early 1980's, a virus was isolated and named hepatitis delta virus. These five different hepatitis viruses have distinct replication pathways and are major health concerns. They have become an important topic for teaching to graduate-level and medical students. Hepatitis Viruses provides a comprehensive, up-to-date review of these viruses to readers. Each chapter is written by one of the top researchers in the field, and topics include: the epidemiology and the natural history of infection of these viruses, the molecular biology and the replication cycle of individual hepatitis viruses, host-virus interactions and the pathogenesis of hepatitis viruses, the immunology of hepatitis viruses, the relationship between hepatitis viruses and hepatocellular carcinoma, the viral vaccines and antiviral drugs. This book can serve as a supplemental reading material to graduate students and medical students, and to any researcher who would like to learn more about hepatitis viruses.

Few fields of medicine have witnessed such impressive progress as the diagnosis and treatment of liver tumors. Advances in imaging technology, the development of novel contrast agents, and the introduction of optimized scanning protocols have greatly facilitated the non-invasive detection and characterization of focal liver lesions. Furthermore, image-guided techniques for percutaneous tumor ablation have become an accepted alternative treatment for patients with inoperable liver cancer. This book provides a comprehensive and up-to-date overview of the role of diagnostic and interventional radiology in respect of liver tumors. The volume moves from background sections on methodology and segmental liver anatomy to the main sections on the diagnosis of benign and malignant liver lesions. An integrated approach, focused on the correlation of ultrasound, CT, and MR imaging findings, is presented. Finally, a full section describes the principles, methods, and results of percutaneous tumor ablation techniques.

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 by the Honorary President of the Symposium, Professor Herbert Thaler, from Vienna. Others followed, and in 1980 JA1/4rgen Ludwig, one of the speakers of this symposium, introduced the name non-alcoholic steatohepatitis' or NASH. In a Consensus Symposium organized by the National Institute of Health (NIH) in Washington, USA, in December 1998, 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, our knowledge of epidemiology, aetiology, and pathogenesis is full of gaps, especially for NASH. Therefore, it is the purpose of this book to show the state of the art, to discuss recent scientific data, and to suggest possible treatment strategies, hoping to stimulate clinicians as well as scientists.

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.

Portal hypertension is causally related to major complications of chronic liver disease like upper GI tract bleeding, ascites formation, portosystemic encephalopathy and bacterial infections. In recent years, new approaches have increased our knowledge of the underlying pathobiological events of these complications. Accordingly, new promising treatment modalities have been developed and introduced into clinical trials. This book, the proceedings of the 79th Falk Symposium in Freiburg-im-Breisgau, Germany, 17--19 June 1994, presents the latest developments in the field, including a section which describes the role of portal hypertension in the pathogenesis of complications of chronic liver disease. Also covered is the therapeutic management of portal hypertension and its consequences as well as the latest endoscopic, interventional and surgical treatment options. This book is essential reading for those whose interests range from anatomy and pathobiology through to practical recommendations for treatment of portal hypertension.

Vascular Liver Disease: Mechanisms and Management covers all of the disease entities that stem from abnormalities that affect the hepatic vasculature. This multi-authored text includes the mechanisms and management of intrahepatic vascular disease, including the most common cause of vascular disease of the liver, cirrhosis. Other less common diseases of the liver vasculature are also covered such as sinusoidal obstruction syndrome (previously known as veno-occlusive disease), portal vein thrombosis, the Budd-Chiari syndrome and congenital vascular malformations. These entities, although rare, are a challenge to physicians and physician scientists. Although many textbooks have been written on the consequences of cirrhosis on the liver vasculature, this is the only volume that focuses on the liver vasculature as a separate entity, providing an innovative approach to liver disease management. Vascular Liver Disease: Mechanisms and Management will be of great value to clinical investigators and basic scientists interested in the liver circulation as well as clinical gastroenterologists and hepatologists, hepatobiliary surgeons and transplant surgeons, and to interventional radiologists with a particular interest in the liver.

The most recent developments in research on hepatic encephalopathy, inborn hyperammonaemic syndromes and nitrogen metabolism, including clinical aspects, were presented by international acknowledged experts in this active research field at the 12th International Symposium on Hepatic Encephalopathy, which was held from June 1 to 4, 2005 in Solingen, Schloss Burg, Germany. This book comprehensively summarizes the most important novel issues on hepatic encephalopathy and nitrogen metabolism and is of interest not only for scientists in the field, but also for interested clinicians. This update of present knowledge will provide a platform for future research in the field of hepatic encephalopathy and nitrogen metabolism.

Hepatitis C Virus and Liver Transplantation is designed to provide a comprehensive and state-of-the-art overview of the major issues specific to the field of liver transplantation and hepatitis C virus infection. The sections of the book have been structured to review the overall scope of issues of recurrent hepatitis C in different complex settings, including retransplantation, HIV-coinfected patients or in the setting of suboptimal graft donors. This book provides up-to-date information on the application of new therapies to the field of liver transplantation. It provides the most recent data on their efficacy, the management of side effects, as well as the potential interactions and specific problems associated with their use in the transplant setting. Finally, an appraisal of the risks and benefits of using organs from anti-HCV positive donors is presented. This book provides concise and actual materials for several important topics that are simply not adequately covered by current available literature. Hepatitis C Virus and Liver Transplantation will provide a unique and valuable resource in the field of liver transplantation and will be of great value to Hepatologists, Transplant and Abdominal Surgeons, Oncologists, as well as Fellows and Residents training in these fields.

Cytokines are synthesized and secreted in the liver by Kupffer cells, and are important for inflammation processes, the non-specific immune response, and probably the destruction and removal of tumour cells. The production of signal substances such as tumour necrosis factor-alpha, interleukin 1 and 6, and interferon alpha/beta is regulated by a complex set of pathways, which can also be modified by cellular mediators, e.g. prostaglandins, growth factors and cortico-steroids. Signal exchange between different cell types in the liver is important for the synthesis of acute phase proteins, liver fibrosis, permeability and liver regeneration. This has clinical implications for hepatitis, cirrhosis and liver transplantation. This book contains the proceedings of the 78th Falk Symposium (Part II of the Gastroenterology Week, Freiburg, 1994) held on 15--16 June and brings together clinicians and researchers worldwide to discuss the role of cytokines in hepatology.