Hepatocytes account for approximately 80% of the liver mass and play a significant role in various aspects of liver physiopathology, exhibiting unrivaled complexity and diversity of functions. In Hepatocytes: Methods and Protocols, expert researchers provide the reader with methods, technical protocols, and review chapters focusing on selected areas of hepatocyte biology including isolation, culture, differentiation and stem cells, and hepatocyte use in clinical, basic, and applied research. With a specific emphasis on human hepatocytes, the volume presents chapters covering subjects including hepatocyte culture models, cryopreservation methods, differentiation assessment, liver ontogenesis, production of hepatocytes from stem cells, drug/xenobiotic metabolism, toxicity and transport, bile acid and blood coagulation factor production, infection by HBV and HCV, humanized animals, biortificial liver devices, hepatocyte transplantation. As a volume in the highly successful Methods in Molecular Biology (TM) series, protocol chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Hepatocytes: Methods and Protocols will be useful to all those who are currently using or planning to use human, or animal, hepatocytes to investigate any aspect of liver physiopathology or who are interested in liver development or liver stem cells and liver biotherapy.

This book, based on the experience of a single large referral center, presents the characteristic findings obtained when using MR imaging and MR cholangiopancreatography (MRCP) to image the biliary tree and pancreatic ducts in a variety of disease settings. An introductory chapter is devoted to technical considerations, anatomy, and developmental anomalies. Subsequent chapters then present in detail the MR imaging and MRCP findings observed in choledocholithiasis, inflammatory and neoplastic disorders of the bile ducts, acute and chronic pancreatitis (according to etiology), and different pancreatic neoplasms. Dynamic MRCP with secretin stimulation is also illustrated, documenting both normal and abnormal responses of the pancreatic duct system to secretin. Readers will find this book to be an excellent aid to the interpretation of MR imaging and MRCP findings in patients with biliary and pancreatic disease.

Due to the latest developments in magnetic resonance imaging for the evaluation of liver pathology, a second, completely revised and enlarged edition of this book was felt necessary - despite only three years having elapsed since the first edition. All chapters from the first edition have been revised and enriched with additional illustrations and information. New chapters have been added covering important and highly relevant topics, among which imaging of pseudolesions, imaging of neoplastic diseases in pediatric subjects, imaging of bile ducts, MR angiography and imaging pre and post liver transplantation. Particular attention has been paid to the differential use of contrast agents with emphasis placed on the authors' broad experience of MR imaging of focal liver lesions using different contrast agents. The diverse mechanisms of action of all MR contrast agents applicable for liver imaging are explained in detail and comparative examples are provided. As was the case with the first edition, this book will prove invaluable to radiologists wishing to further expand or consolidate their routine approach to MR imaging of the liver.

Liver disease is a widespread and increasing problem throughout the world, however little is published on how different types and degrees of liver dysfunction affect the body's ability to handle medicines."Drugs and the Liver" is designed to assist practitioners in making pragmatic choices for their patients. It aims to: enable the practitioner to assess liver function using biochemical markers, other tests, signs, symptoms and disease knowledge; identify which pharmacokinetic and pharmacodynamic parameters of a drug are likely to be affected by different types of liver disease; and consider the impact of a drug's side effects on a patient with liver disease.This practical guide covers background information on liver function, the principles of drug use in liver disease and includes a section of worked examples of commonly asked questions. It will be invaluable to clinical pharmacists and anyone making medicine choices in patients with liver impairment.

Surgery is the gold standard treatment of colorectal liver metastases. Patients management had a dramatic evolution during the past years: more accurate diagnostic tools and more effective chemotherapy regimens have been introduced and surgical indications have been widely broadened. A multidisciplinary treatment is now mandatory, involving oncologists, radiologists an gastroenterologists. However, many topics are still debated. In the present book all aspects of surgical treatment of colorectal liver metastases are analyzed based on a systematic, updated analysis of the literature. Aim of this book is to provide surgeons, oncologists and radiologists a clear overview of the state-of-the-art of treatment of colorectal liver metastases.

Understanding Liver Cancer is a concise and up-to-date review, which discusses diagnosis, management, patient care, current and emerging therapies, and useful resources that clinicians can provide to their patients. Busy healthcare professionals who want a quick review of liver cancer as well as a summary of current therapies will benefit from this succinct text."

Portal hypertension is the abnormal pathophysiologic state that develops in liver cirrhosis and certain other disorders with characteristic clinical and hemodynamic features. There has been great progress in our under standing and management of portal hypertension, particularly in the diagnostic and therapeutic approaches. The so-called Banti's syndrome, a disorder whose existence had long been questioned, is now a well-defined portal hypertensive disease. The recently introduced Doppler ftowmetry is currently yielding new information on portal hemodynamics. Endoscopic sclerotherapy and beta-blockers have come to be widely used in the man agement and prevention of variceal bleeding. In spite of all these advances, a number of unsolved questions remain, such as whether sclerotherapy, pharmacotherapy or surgery is warranted for prevention of bleeding, which is more effective as an elective treatment, the surgical or endoscopic approach, and whether surgical portacaval shunt should be totally replaced by selective shunt operations. These new developments and problems are clearly and comprehensively described and discussed by the foremost authorities in 44 chapters, which are divided into five sections: 1) Patho physiology, 2) Hemodynamic Investigations, 3) Imaging Investigations, 4) Clinical and Pathological Features, and 5) Esophageal and Gastrointestinal Bleeding. The primary goal of this monograph, to provide a framework of patho physiology of portal hypertension with authoritative descriptions of the clinical and laboratory manifestations of various portal hypertensive dis orders, has clearly been achieved by these excellent contributions.

As we approach the end of this millennium, enteric diseases remain impor tant public health problems. In many parts of the world, sanitary measures have advanced little over the last century, although some of the governments in those areas are striving to improve facilities for sanitation and to educate their people in proper handling of food, water, sewage, and other modes of transmission of pathogenic microbes. Even in highly developed countries, outbreaks of diarrheal diseases occur today. Globally, the annual morbidity from enteric infections is estimated at several billion and deaths at several million per year. In this volume, descriptions of some of these diseases, of immunity that results from them, of clinical studies that promote under standing of individual and community immunity, of molecular factors of pathogenesis, and/or of advances in vaccine development have been pro vided by leading researchers. At present, the application of molecular methods is enhancing the identification of protective antigens of many microorganisms. In addition, new methods for design and delivery of vac cines are being devised. Perhaps then more effective tools for reducing at least some of these diseases will be available within the next decade. Lois J. Paradise Herman Friedman Mauro Bendinelli vii Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv LOIS J. PARADISE 1. Indigenous Microorganisms as a Host Defense 1 KENNETH H. WILSON 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Composition of Intestinal Biota. . . . . . . . . . . . . . . . . . . . . . . . 2 3. Molecular Approaches to Determine Composition of the Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Role of the Host in Determining the Composition of the Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Since the discovery of superoxide dismutase more than three decades ago, there has been rapid growth in the knowledge of oxidative stress and disease. This volume containing the proceedings of the 13th Yamaguchi Symposium on Liver Disease includes discussion of the direct cellular effects of hepatitis C virus (HCV) proteins on hepatocytes and reviews evidence that oxidative stress caused primarily by the HCV core protein plays a key role in disease pathogenesis. Also included are chapters on new aspects of oxidative stress and liver disease such as carbon monoxide as a regulator of liver microcirculation, hepatic iron accumulation and the incidence of hepatocellular carcinoma, and oxidative stress in the absence of inflammation in hepatocarcinogenesis. This collection of papers from the Yamaguchi Symposium creates a valuable reference resource for physicians and hepatologists.

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.

Movement disorder specialists, general neurologists, hepatologists, general gastroenterologists, and psychiatrists are the specialists who will most likely see some Wilson's disease patients during their careers. See them - yes. Recognize and diagnose them - maybe. If you are in one of these specialties, and a patient with tremor, hepatitis, cirrhosis, apparent Parkinsonism, or mood disorder, is referred to you, will you appropriately recognize the possibility that the underlying diagnosis may be Wilson's disease? Wilson's disease is both treatable and reversible, and commonly misdiagnosed. This book aims to change this with comprehensive coverage of every aspect of Wilson's disease, from well-catalogued, easy-to-use clinical diagnostic tools to treatment methods to molecular biology. Dr. Brewer is the world's leading expert on Wilson's disease, seeing and caring for over 300 patients with the disease during the last 20 years. He is a professor of human genetics at the University of Michigan.

Since the 1st Yamaguchi Symposium on Liver Diseases in 1989, this series of symposia has provided opportunities for exchanges of information on the topic between leading Japanese hepatologists and internationally renowned scientists. Somewhat unusually for meetings held in Japan, the official language of the symposium is English. The pro ceedings of these symposia are published under the title Frontiers in Hepatology and distributed worldwide. The 12th symposium was held on December 9 and 10,2000, at the ANA Hotel, Ube, Japan. The theme selected by the Organizing Committee was "Growth, Proliferation, and Apoptosis in Hepatocytes;' each of which is important in the understanding of the pathophysiology of intractable liver disease. Nine Japanese hepatologists were invited to give presentations, as was leading u.S. researcher Professor D.A. Brenner, recently elected editor-in-chief of the journal Gastroenterology. The reports given at the two-day meeting were valuable in furthering our under standing of the complicated signaling system involved in hepatocyte differentiation, proliferation, and apoptosis. Progress in this field is rapid, and another symposium on the same theme will be held in the near future. We believe that these proceedings are useful in summarizing current information on this important topic. The Organizing Committee would like to express special thanks to all participants and to the Viral Hepatitis Research Foundation of Japan for its continuing financial support."

The condition of prolonged obstructive jaundice with patent bile ducts was first described in 1851 by Addison and Gull of Guy's Hospital, London. The term primary biliary cirrhosis (PBC) was defined in 1950 by Ahrens and colleagues of the Rockefeller Institute, New York. The condition was considered rare but this changed in 1965 with the discovery of a definitive diagnostic serum mitochondrial antibody test and the recognition that a raised serum alkaline phosphatase value, often discovered incidentally, could be a diagnostic pointer. If the diagnosis is made earlier, the end stages are rarely reached as death is replaced by liver transplantation. On November 6th 1997, in Chicago, an International Faculty discussed in depth the clinical features, pathogenesis and treatment of PBC, no longer considered a rare disease. The course of PBC is long, but some 18 years after the discovery of a positive mitochondrial antibody test in a symptom free patient with normal serum biochemistry, 83% will have developed abnormal tests and 76% will be symptomatic. Identification of those who will progress rapidly is difficult. The serum antimitochondrial profile may be useful but this is a very specialist technique. Mathematical prognostic models are useful in therapeutic trials and in the selection and timing of patients for liver transplantation but have limited value in individual patients. An increasing serum bilirubin level remains the most important indicator of rapid progression. Its value however can be negated by the use of ursodeoxycholic acid which has a bilirubin-lowering effect."

A concise, practical guide to the diagnosis and treatment of liver disease. Authoritative and practical, this important new book not only spells out the advantages and limitations of the latest diagnostic tests, but also provides numerous algorithms for evaluating patients and treating the liver problems commonly encountered by primary care physicians. Here, too, the reader will find described the nuances of serological tests for the detection of viral infections and how best to use invasive and noninvasive radiological tests in specific circumstances. Common complications are fully discussed and detailed practical information is given on how to recognize the patient's immediate problems and deal with them effectively. This book's numerous diagrams, clinical "pearls", and cost comparisons will clarify the often complex and bewildering array of conditions associated with liver disease and make it a definitive and indispensable guide for primary care physicians, medical students, and residents.

This book intends to provide a comprehensive and up-to-date description of the newest techniques in minimally invasive liver surgery. The treatment of liver diseases comprises a significant component of the practice of any general surgeon working either in the academic, general and community hospitals. With the rapid expansion of knowledge and technology also the liver has been approached laparoscopically in a few specialized centers with well recognized advantages for the patients. Now this large amount of experience will be made universally available through this book. After a concise description of the main tools and technology necessary to carry out a safe laparoscopic and/or robot-assisted liver surgery, details of operative techniques will be illustrated. Each chapter will consist of an introduction, a summary of the indications and contraindications of specific operative procedures and a detailed description of each surgical procedure, including the potential complications of both the surgery and the postoperative care. A special effort will be done to provide informative and accurate illustrations and pictures, that will be completed by the DVD containing the movies illustrating the technical procedures performed by the leading European liver surgeons.

This book is directed towards post-graduates who have passed Part I of the examination for Membership of the Royal College of Physicians and are preparing for Part II. However, it is hoped that physicians at all stages of their careers will find some parts that interest them. Most of the material has appeared in the Hospital Update series, 'Preparation for MRCP', but this has been modified and expanded; many useful points arising from correspondence relating to the series have been included, and the authors would like to express their thanks to those who have written. It is not intended that this should be used as a work of reference, although there is detailed discussion of some subjects. Only the written part of the examination is dealt with in detail, but the introduction contains hints on tackling the clinical sections which the authors hope the candidates will find valuable. There is, however, no substitute for clinical practice under supervision. The questions in Vll PREFACE the written section of the examination require short answers so that marking may be easy and objective. This book contains questions similar to those that may be encountered in the examination, but the answers have been expanded as a basis for discussion. It is hoped that this will encourage the candidate to read around the subjects covered, and the authors recommend that the questions are used as a basis for group discussion, as answers other than those in the text may be considered.

A series of international symposia on viral hepatitis and liver disease has been held triannially, and called the "Olympics" of this research field. Our book presents the results of the eighth of these "Olympiads" which for the first time, was held in Asia (May 1993, Tokyo). Due to the rapid progress in research on both basic and clinical aspects of viral hepatitis and liver disease, the state of the art in this field is continually being updated, and our book provides a broad and in-depth survey of current work. The major topics in our book include molecular biology of the five known hepatitis viruses (HAV, HBV, HCV, HDV, and HEV), clinical implications of genetic variants of HBV and HCV, interferon treatment of HCV-related liver disease, and worldwide epidemiology and control of viral hepatitis. New subjects not seen in previous books, such as genotypes of HCV, are also covered. Expanding knowledge about the heterogeneity of the HCV genome has revealed a great variety of genotypes as well as their association with host pathogenesis and their varying responsiveness to interferon therapy. The first promising results of efforts to develop a hepatitis C vaccine are also presented. Finally, compared with its predecessors, our book contains many more papers from Asian countries, where the prevalence of viral hepatitis and liver disease is the highest in the world.

J. DE GROOTE One of the most ominous and troublesome complications of the liver disease is the appearance of hemorrhagic phenomena. Many careful clini- cal observations about the relationship of liver function and of bilia- ry tree pathology have been published. A vast amount of research work has been devoted to the subject. The severity of the hemorrhagic disor- der is usually in relation to the liver disease. In mild chronic hepa- titis or short lasting obstruction slight subcutaneous or mucosal blee- ding may (lraw the attention of the patient and the doctor, but they are as such far from dangerous. However in acute hepatic insufficiency, in biliary cirrhosis the bleeding tendency is to be considered as a life threatening complication in about half of the cases. Moreover coagulation disturbances aggravate bleeding not only from ruptured oesophageal or gastric varices but also from gastritis or peptic ulcer. 11enometrorrhagia, epistaxis and gingival bleeding may be very trouble- some in these conditions. The use of diagnostic procedures sucl. as liver puncture biopsy and peritoneoscopy are often impossible when platelets and prothrombine time are too low. In order to overcome this difficul- ty a procedure has been worked out taking a biopsy through a trans- jugular catheter placed in the hepatic vein. If a bleeding from the liver occurs it will be in the circulatory system and not cause any trouble.

In 1983 and 1984, I had the pleasure of being invited to Europe for the Cour- se of Hepatobiliary Surgery started by Professor Hepp and continued by Pro- fessor Bismuth. In these courses, I demonstrated many slides and movies of intraoperative echography that Makuuchi, one of my staff members, had made using the transducer that he was the first to develop. The topic of Intraoperative Echography had an enormous impact on the audience, and its use has since spread rapidly over the European countries, by virtue of the first Italian edition of Professor Gozzetti's book on Intra- operative Echography and Professor Bismuth's monograph on the same top- ic. I had been, therefore, unwittingly a very fortunate transmitter of intra- operative echography to Europe by means of Makuuchi's slide file. I am extremely honoured that the Italian Edition written by Gozzetti, Maz- ziotti and Bolondi has been dedicated to me. Also in this English Edition, Professor Gozzetti very kindly asked me to write a few words. It is an extra- ordinary pleasure for me to emphasize how this book is easy to read and understand, maybe by virtue of the profound Italian tradition of artistic expression since the Renaissance. On the other hand, a variety of series of intraoperative echographic images as well as resected specimens are arranged in an excellent manner.

"This attractive, compact handbook offers highly practical, to-the-point guidance to residents and students. The Handbook gives equal weight to both diagnosis and therapy, includes an easy-to-reference emergency section, and maintains a focus on practical disease management. The book's anatomically organized sections are supplemented by special sections on management of GI emergencies and the Top 10 GI Problems, including pertinent algorithms and practice guidelines from the American Gastroenterology Association. Useful appendices provide CT images of common GI problems, normal laboratory ranges, and links to useful websites"--Provided by publisher.

Acute liver failure (ALF), or fulminant hepatic failure, is a distinct clinical syndrome which crosses medical disciplines. A relatively rare condition, ALF remains a major focus of clinical and research attention and with the advent of transplantation, the importance of understanding management of ALF has taken on a new urgency. In this 1997 volume, the editors bring together a distinguished team of contributors to describe the aetiology, pathology and treatment of this important syndrome. Also covered are consensus techniques in liver transplantation for ALF patients, as well as descriptions of artificial and bioartificial liver assist devices. A section on future treatments includes hepatocyte transplantation, auxiliary grafts and other temporary liver support. Notable for the high level of authors' expertise, this comprehensive volume should prove invaluable to internists, gastroenterologists, surgeons, and intensive care providers.

Liver Transplantation: Challenging Controversies and Topics grew out of a need I perceived within the fields of transplant hepatology and liver transplantation. Liver transplantation has rightly gained recognition as an established therapy for end-stage liver disease. Few would argue that liver transplantation is one of the few truly lifesaving and life-altering treatments within medicine and surgery. Not many realize that 20 years passed from the time of the first human liver transplantation in 1963 to its acceptance as therapy by the 1983 NIH Consensus Conference on Liver Transplantation. In 2008, 25 years will have passed since the 1983 NIH conference-a mere 25 years for a field that has provided patients hope, doctors options, and to some the "gift of life. " Many issues in liver transplantation involve indications, patient selection, and outcomes after transplantation-these are standard topics, covered by textbooks of hepatology and transplantation. In contrast, the field of liver tra- plantation is young, evolving, dynamic, and issues and decisions are often controversial. Thus, Dr. Trotter and I, as well as our colleagues at the University of Colorado, felt that a text with a different focus was required, one that highlighted controversy and challenged dogma. Out of this perceived need emerged Liver Transplantation: Challenging Controversies and Topics. To meet the transplant community's need for emerging information about liver transplantation, Dr. Larry Chan, Dr. Igal Kam, and I initiated the Controversies in Transplantation Conference.

- Written by international contributors including specialists in surgery, hematology and oncology.

- The information is presented in an instructive manner, allowing the phycisian to utilize the content immediately.

- Discusses new techniques such as minimally invasive approaches to surgery and new cancer treatments.