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.

The meeting which took place in Rome on November 19th and 20th of 1982 is easily the best meeting on hepatic coma that I have ever attended, and I have attended many. It was an exceedingly we- planned meeting with prolonged opportunity for discussion, and there was genuine interplay and exchange of ideas (not the usual picture of a rushed meeting with investigators presenting their own point of view and talking past each other without a meaningful ex change) which took place in Rome. My co-editors and I hope that the published transcript, which of course can only reflect what transpired in Rome on those two days, does justice to a very intellectually exciting and gratifying ex change of ideas. L. Capocaccia, J. E. Fischer and F. Rossi-Fanelli v CONTENTS Introduction 1 SECTION 1: PATHOGENETIC PROBLEMS IN HEPATIC ENCEPHALOPATHY Ammonia: The old and the new • • . • • • . • . • • • . • . • 5 L. Zieve Role of synergism in the pathogenesis of hepatic encephalopathy • • • • . • • . . . . • 15 L. Zieve y-Aminobutyric acid receptors in experimental hepatic encephalopathy •. •. • • 25 M. L. Zeneroli, ~. Baraldi,and E. Ventura A possible role for excitatory neurotoxic amino acids in the pathogenesis of hepatic en 41 cephalopathy • • • • • • • • • • • • • • • F. Moroni, G. Lombardi, G. Moneti, D. Pellegrini and C.

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

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. This book 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.

Brain dysfunction is a major clinical problem in intensive care, with potentially debilitating long-term consequences for post-ICU patients of any age. The resulting extended length of stay in the ICU and post-discharge cognitive dysfunction are now recognized as major healthcare burdens. This comprehensive clinical text provides intensivists and neurologists with a practical review of the pathophysiology of brain dysfunction and a thorough account of the diagnostic and therapeutic options available. Initial sections review the epidemiology, outcomes, relevant behavioral neurology and biological mechanisms of brain dysfunction. Subsequent sections evaluate the available diagnostic options and preventative and therapeutic interventions, with a final section on clinical encephalopathy syndromes encountered in the ICU. Each chapter is rich in illustrations, with an executive summary and a helpful glossary of terms. Brain Disorders in Critical Illness is a seminal reference for all physicians and neuroscientists interested in the care and outcome of severely ill patients.

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.

In recent years there has been an increasing need for transplantation, but the number of donor livers available has increased only slightly, despite intensive public relations activities. New concepts in the field of transplantation, for instance the transplantation of living donor organs or the splitting of organs, are urgently required, to safeguard the treatment of patients with severe liver disease. The development and clinical application of cell therapy for patients with liver disease could soon present a significant enhancement of the therapeutic options. The aim of such cell therapy is to repair or improve the biological function of the chronically and acutely damaged liver. Even though systematic trials are not available, individual case reports and small series already show promising clinical results. Present concepts of cell therapy for liver diseases based on the use of primary hepatocytes have recently been considerably extended through new data on the biology of stem cells. The adult haematopoetic stem cell as a pool for hepatocyte grafts - what would be the perspectives for the clinical application? This book is the proceedings of the Falk Symposium No. 126 on `Hepatocyte Transplantation' (Progress in Gastroenterology and Hepatology Part III) held in Hannover, Germany, October 2-3, 2001, and is a forum for basic research, but also for questions concerning clinical applications in the field of hepatocyte transplantation.