Immune Reactions In Liver Disease

The role of the immune response in both the pathology of liver disease and in the modulation ofliver injury has been the subject of intense research. This book aims to present the current understanding of the involvement of the immune response in liver disease. The first chapters examine the role of the immune response in viral infections of the liver. These viruses cause hepatitis of varying severity and it is thought that many of the mechanisms responsible for liver cell injury are immunologically mediated. In addition three of these viruses, hepatitic B, C, and D, are associated with persistent infection and chronic liver disease. The role of the immune response in viral persistence is discussed. Further chapters are devoted to the three major autoimmune liver diseases which are thought to be the result of loss of tolerance to autologous liver tissue. There has been much recent research on cellular immune responses in these diseases but knowledge of the immunological processes which lead to the breakdown of tolerance and the mechanisms of tissue damage are limited. Other research has concentrated on the identification of the antigens which are the targets of this immune response. Linkage disequilibrium between MHC alleles and autoimmune diseases has suggested a role for immunogenetic factors.

Drug-Induced Liver Injury, Volume 85, the newest volume in the Advances in Pharmacology series, presents a variety of chapters from the best authors in the field. Chapters in this new release include Cell death mechanisms in DILI, Mitochondria in DILI, Primary hepatocytes and their cultures for the testing of drug-induced liver injury, MetaHeps an alternate approach to identify IDILI, Autophagy and DILI, Biomarkers and DILI, Regeneration and DILI, Drug-induced liver injury in obesity and nonalcoholic fatty liver disease, Mechanisms of Idiosyncratic Drug-Induced Liver Injury, the Evaluation and Treatment of Acetaminophen Toxicity, and much more. Includes the authority and expertise of leading contributors in pharmacology Presents the latest release in the Advances in Pharmacology series

Howard C. Thomas In normal subjects the regulatory apparatus of the immune system permits responses to foreign antigens but suppresses those directed to "self' components. Autoimmune disease occurs as a failure ofthis system either as a result of a primary defect in the regulatory apparatus (primary autoimmunization) or because of a change in the antigenicity of the tissues (secondary autoimmunization). Autoaggressive reactions are characterised by the presence of autoantibodies. When these are directed to membrane displayed antigens (Fig. 1) they are probably of importance in the lysis of hepatocytes. Those directed to cytoplasmic antigens may be useful diagnostically but are of unknown pathogenic significance. When no extrinsic aetiological factor can be identified, the process is assumed to be the result of a failure ofthe regulatory system, allowing the spontaneous expansion of a clone of autoreactive lymphocytes. The defect may be generalised or specific to certain groups of self-antigens and thus the autoimmune disease may be either multi- or unisystemic. The recent development of techniques to enumerate and measure the functional activity of the suppressor lymphocytes which control the effector limbs of the immune system has enabled investigators to test whether the various purported autoimmune diseases do have as their basis a generalised defect in immunoregu lation. Assessment of antigen-specific immunoregulatory function is, however, not yet readily available. liver Membrane I Antigen (LIM) I Liver I HLA, A, B, C, Sensitisation to Specific -;::!IIIL. .

Liver Immunology: Principles and Practice, Second Edition begins with important information about the epidemiology and mortality of liver disease worldwide. This information is followed by chapters related to basic immunology, application of liver immunology for diagnosis, and several excellent chapters that provide a solid foundation for understanding immune-mediated liver disease, including those associated with the biliary tree. A chapter on non-hepatic manifestations of immune mediated liver disease helps provide context for how these diseases affect the patient overall. In addition, chapters discuss various discrete immunologically-mediated infectious liver disorders including those related to bacteria, parasites, and all of the classic viruses. Chapters on the traditional autoimmune liver diseases -- primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis as well as overlap syndrome – are also included. The breadth of this comprehensive second edition is highlighted by chapters on alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver disease, among others. This invaluable new edition ends with a forward-looking view of future directions and how the field might meet the challenge of refractory patients. Developed by a renowned group of authors, Liver Immunology: Principles and Practice, Second Edition will again serve as a comprehensive textbook by providing an excellent overview for this rapidly evolving field. It greatly adds to the understanding of the pathogenesis of these diseases, while also providing novel insights that can be harnessed into helping improve the care of patients afflicted with various immune-mediated diseases. This volume will again be a must-read for clinicians at all levels, investigators and students.

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.