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, the proceedings of Falk Symposium 163 Chronic Inflammation of Liver and Gut, held in Hangzhou, P.R. China, on March 14--15, 2008, presents the most recent progress in chronic inflammatory diseases of liver and gut. It focusses on molecular understanding, the therapeutic state of the art and future options of treatment.

The first part of the book concentrates on basic and clinical aspects of IBD. Chapters demonstrate the role of the immune system, genetic factors and the intestinal microflora in IBD, and give an evidence-based update on the current diagnostic and therapeutic options and present future perspectives for the management of IBD. The second part is devoted to chronic liver diseases with particular focus on the liver as an immune organ, treatment strategies of viral hepatitis and liver fibrogenesis. The final part deals with basic and clinical aspects of liver cirrhosis, hepatocellular carcinoma and liver transplantation. The book concludes with an outlook on therapeutic options of hepatic stem cells. Throughout, international experts from the USA, the People s Republic of China and Europe contribute their experience in different aspects of the mechanisms and management of chronic inflammatory diseases of liver and gut. "

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.

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.

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.

In this issue of Clinics in Liver Disease, guest editor Dr. David Bernstein brings his considerable expertise to the topic of The Liver and Renal Disease. The presence of liver disease in patients with chronic renal disease makes the management of both conditions more challenging. In this issue, top experts in the field address many aspects of the treatment and management of these co-existing conditions. Contains 13 relevant, practice-oriented topics including hyponatremia in cirrhosis; pathophysiology of hepatorenal syndrome; definitions, diagnosis, and management of hepatorenal syndrome; renal replacement therapy in patients with acute liver failure and end-stage cirrhosis awaiting liver transplant; simultaneous liver/kidney transplantation; and more. Provides in-depth clinical reviews on the liver and renal disease, offering actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field. Authors synthesize and distill the latest research and practice guidelines to create clinically significant, topic-based reviews.

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.

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.

Liver Cancer, the inaugural volume in the M.D. Anderson Solid Tumor Oncology series, provides the general surgeon, surgical oncologist, and medical oncologist with the most up-to-date and current standard of multimodality care for hepatobiliary cancer. Surgical approaches, chemotherapy, immunotherapy, gene therapy, and radiotherapy are all presented, giving the practitioner a much needed, comprehensive perspective on all aspects of patient care. The MD Anderson Solid Tumor Oncology series features cutting-edge, indepth information of vital interest to all practitioners in today's captitated financial milieu. Providers must understand how their component of care interdigitates with the varied medical and surgical teams and apply multimodality approaches to their practice environments.

The beginning of a new millennium is an ideal opportunity to look back, to contemplate the present and to envisage what the future might have to offer. This seems particularly appropriate for the rapidly developing field of hepatology. Therefore, the aim of the Falk Symposium 117, Hepatology 2000, held in Munich on 4-6 May 2000, was to offer state-of-the-art information on the most important aspects of hepatology and to discuss the challenges of the future. The presentations were given by experts in their respective areas, providing an update and at the same time incorporating the most recent developments. These proceedings, a tour d'horizon of hepatology at the highest clinical and scientific level, is dedicated to Gustav Paumgartner who has retired from his duties as chairman of the Department of Medicine II at the University of Munich- Grosshadern. The scientific organisers take this opportunity to thank their academic teacher and to honour his lifelong engagement and achievements in hepatology. This book is cordially dedicated to him.

Chronic hepatitis has been in the focus of intense scientific research for decades. Recently, considerable progress and exciting new insights into pathogenesis and resulting therapeutic strategies have been made. Replication of hepatitis B and C viruses and details of life cycle in the host have been well characterised. Immunology in general and immunopathology of the liver in viral and autoimmune hepatitis have shown more specific mechanisms of host defence and new models of autoimmune aggression have been developed. The role of apoptosis in liver damage is now well appreciated and has been analyzed precisely. Essential steps of fibrogenesis as a consequence of chronic liver damage are better understood by now and new strategies for its prevention have evolved. Chronic hepatitis is the leading cause of liver cell carcinoma, the molecular basis of which has been more clearly elucidated. This increasing knowledge will provide a sound basis for more effective therapy in chronic hepatitis and its life-threatening consequences. This book, the proceedings of the Falk Workshop on Chronic Hepatitis, held in Cologne, Germany, on January 27-28, 2000, brings together experts from different fields of research such as virology, immunology, pathology, cell and molecular biology, as well as clinical medicine, and disusses in depth the novel findings in basic and clinical research.

This text provides a comprehensive, state-of-the art review of this field, and will serve as a valuable resource for students, clinicians, and researchers with an interest in hepatitis B. The book reviews new data about basic and translational science including the viral life cycle, the immunopathogenesis of virus induced chronic hepatitis, the mechanism of virus induced liver cancer, and their potential applications for the clinical management of patients. The clinical aspects of this chronic viral infection are reviewed in detail with important chapters on the global epidemiology, the natural history of the disease, co-infections with its satellite virus HDV or HIV, and management of special patient populations. A major emphasis is made on the management of antiviral therapy and the recent international guidelines for the treatment of hepatitis B. Finally, the book reviews the current state of the art regarding immunoprophylaxis to prevent the spread of the virus and its major clinical consequences. The new advances and perspectives in the development of improved antiviral treatments are also discussed. Hepatitis B Virus in Human Diseases will serve as a very useful resource for students, physicians and researchers dealing with, and interested in, this challenging chronic viral infection. It will provide a concise yet comprehensive summary of the current status of the field that will help guide patient management and stimulate investigative efforts. All chapters are written by experts in their fields and include the most up to date scientific and clinical information.

Encephalopathy and Nitrogen Metabolism in Liver Failure contains research reports and state-of-the-art reviews that were presented at the 11th International Symposium on Hepatic Encephalopathy and Nitrogen Metabolism in relation to liver disease, that was held in Amsterdam, The Netherlands from 30 May to 1 June, 2002. Themes covered include the metabolism of ammonia and amino acids in relation to liver disease, the assessment of hepatic encephalopathy (HE), minimal HE, animal models of HE, neuropsychiatric dysfunction in patients with chronic liver disease, the pathogenesis of HE, the astrocyte in liver disease, acute liver failure and cerebral edema, treatment of HE and artificial liver support systems. This volume provides an indispensable source of important new research findings and ideas for clinicians and biomedical scientists working in the field of HE and nitrogen metabolism in relation to liver disease.

Diagnostic and interventional endoscopy has made rapid progress in recent years. Several methods are still under development and need to be properly evaluated. Bile duct diseases may have a negative impact on the liver, so early diagnosis and minimal invasive treatment options are important. Liver transplantation is now established for the treatment of liver failure. Hepatic surgery may lead to problems in the bile ducts which can be treated by endoscopic intervention. A broad spectrum of indications for interventional endoscopy in hepatology exists. This book, the proceedings of Falk Symposium No. 116, held in Basel, Switzerland, October 25 1999 (Part III of the Basel Liver Week 1999), describes the state of the art and new developments in endoscopy for these treatments, and contains chapters by well-known experts from all over the world.

Liver cirrhosis is a major clinical problem worldwide and is associated with significant morbidity and mortality from its complications, such as liver cell insufficiency with coagulopathy and hepatic encephalopathy, portal hypertension with ascites and gastrointestinal bleeding, hepatorenal syndrome, HCC development and others. This volume, the proceedings of Falk Symposium 115 held in Basel, Switzerland, October 22-24, 1999 (Part II of the Basel Liver Week 1999; XI International Congress of Liver Diseases) covers our present knowledge of the aetiologies and early stages of liver cirrhosis development. Based on this information, strategies are discussed that are aimed at the prevention, early diagnosis and therapy of chronic liver diseases, thus preventing their progression to cirrhosis and its complications, including HCC development. The main topics mentioned above are complemented by three state-of-the-art chapters on modern aspects of medicine in general and hepatology in particular as well as their perspectives beyond the year 2000: `Molecular Medicine', `New Hepatitis Viruses' and `Genetic Liver Diseases: Diagnosis and Therapy'. Introductory chapters focusing on the more basic aspects of the biology of live cells as well as on the mechanisms underlying fibrogenesis, cholestasis and inflammation will be followed by a detailed discussion of the clinically most important causes of liver cirrhosis worldwide: hepatitis viruses B, C and D; toxins (alcohol, drugs and others) as well as metabolic liver diseases (haemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, porphyria cutanea tarda and protoporphyria). This book, therefore, will interest clinically oriented basic scientists as well as those in clinical practice, givng an update on many aspects of modern hepatology and its perspectives in the next millennium.

It is now widely accepted that multidisciplinary collaboration and multimodality treatment approaches are important in improving the survival of patients with hepatocellular carcinoma. In this comprehensive textbook, internationally renowned experts in the field present and discuss the various strategies employed in the treatment of the disease. Up-to-date information is provided on the indications for and outcome of a range of treatment options, including surgical resection, liver transplantation, radiofrequency ablation, transarterial chemoembolization, yttrium-90 transarterial radioembolization, and systemic therapy. In addition, important background information is included on biology, pathology, staging, and imaging. This book will be particularly helpful to all professionals and trainees worldwide who have an interest in the diagnosis and treatment of hepatocellular carcinoma.

Because of the increasing burden of hepatitis C and fatty liver disease, there is an explosion in the prevalence of chronic liver failure and hence its complications. The onset of Hepatic Encephalopathy (HE) in these patients has a significant impact on the quality of life, morbidity and mortality. Unfortunately, the approach observed by most clinicians to this complex disorder is minimalistic. Hepatic Encephalopathy provides a comprehensive review on pathophysiology and clinically important aspects in HE. Topics in basic physiology, nitrogen metabolism, new insights into pathogenesis and brain edema are covered in great detail. The authors have made a special effort by simplifying the complex aspects of pathogenesis and diagnosis so that it can be easily understood and applied clinically. This volume also focuses on recent developments regarding diagnoses of subtle forms of HE, also known as minimal or covert HE as well as on new treatments. Hepatic Encephalopathy will be of great value to gastroenterologists, hepatologists, pathologists, medical residents, fellows, internists, and general practitioners who treat patients with hepatic encephalopathy.