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 is written for the primary care clinician to help update knowledge of pediatric endocrinology (with an emphasis on diabetes) from both ancient and modern times. The current and future shortage of pediatric endocrinologists necessitates steady, rejuvenated information on diabetes and other endocrine disorders for primary care clinicians as they care for the child and adolescent with complex endocrine dilemmas and disorders. In view of this shortage and the rapidly increasing knowledge in pediatric diabetes as well as understanding indications for referral to pediatric endocrinologists in the 21st century, au courant assiduous information aimed at primary care clinicians in these areas becomes increasingly important.

Hepatitis B virus (HBV) infection is a problem of global health importance and represents a significant cause of morbidity and mortality world-wide. HBV can be transmitted parenterally, sexually and perinatally. Despite progress on prophylaxis, diagnostic and treatment of HBV infection, it remains one of the major causes of chronic liver disease, cirrhosis or hepatocellular carcinoma. This book presents a compilation of current research including such topics as Hepatitis B and dialysis; Hepatitis B virus infection among middle school students in South Brazil; genotyping and management of chronic Hepatitis B; the risk assessment for Hepatitis B infection and its role in hepatocellular carcinoma; and silencing Hepatitis B virus replication with antiviral Pri-Mir shuttles generated from liver-specific Pol II promoters.

Sex does matter. One of the most compelling reasons for understanding the biological differences, which are not so explained at this time, is that there are striking differences in human disease. The most obvious and best-studied differences between the sexes are in the reproductive systems. Much less study has been done on sex differences in non-reproductive areas of biology. Liver cancer is undoubtedly predominant in men and postmenopausal women. Almost anyone may "feel," but not recognise the sex-associated difference in liver cancer as a fact. How does sex matter in the incidence of liver cancer? After considering the data and examples presented in this book, anyone will be provided unique opportunities to obtain a better understanding of differences of chronic liver disease between the sexes. Some of these differences can be explained by what we now know. Some are unexplained and point to important questions for future study. Being female or male is an important basic human variable that affects health and liver disease throughout the life span. A better understanding the biological mechanisms underlying the sex-associated differences in chronic liver disease would provide valuable information to design care of health and liver disease more effectively for individuals, both females and males.

Rapid advances on molecular studies, manipulation of the mouse genome, the development of a number of animal models, and using these in studies of nonalcoholic fatty liver disease (NAFLD) have provided important insights into the pathogenesis of this relatively common disorder. One of the most crucial advances was to recognise the links among obesity, insulin resistance, inflammation and NAFLD. A growing body of literature has shown that insulin resistance and its liver-related consequence, NAFLD, could be the result of generalised inflammation. Genetic and behavioral factors contribute to increased visceral adipose tissue where increased oxidative stress and lipid peroxidation may contribute to dysregulated production of adipocytokines, fatty acids, and bioactive lipids. This chain of these events may contribute to local and peripheral insulin resistance, a central underlying pathophysiological process that may both cause and result from increased peripheral lipolysis and elevated free fatty acid concentrations in the circulation. Abnormally elevated free fatty acids taken up by organs other than adipose tissue, such as liver and skeletal muscle, contributes to steatosis of these organs (ectopic lipogenesis). Increased muscle and hepatocellular lipid content provides substrates for oxidative stress and lipid peroxidation, and also promotes insulin resistance in both liver and muscle by disturbing their downstream insulin signaling cascades. Insulin resistance further increases peripheral lipolysis in adipose tissue, further elevates circulating free fatty acids, inhibits hepatic fatty acid a-oxidation and increases de novo synthesis of both fatty acids and triglycerides in the liver. Excessively produced triglycerides in the liver are either stored as fat droplets or secreted into the plasma as very-low-density lipoproteins. If this complex mechanism of hepatic fat synthesis and secretion capacity is overwhelmed, excessive triglycerides accumulate within the hepatocytes and manifests as NAFLD. A fatty liver is sensitive to hepatocellular injury and sustained injury can manifest as nonalcoholic steatohepatitis (NASH), NASH-associated cirrhosis, and NASH-associated hepatocellular carcinoma. Specific depletion of hepatic natural killer T cells with consequent proinflammatory cytokine polarisation of liver cytokine production might be one reason for this increased hepatic sensitivity against various stimuli. Only a minority of patients with NAFLD have the necroinflammatory changes of NASH. The development of NASH in patients with NAFLD may be the consequence of secondary abnormalities such as injured and dysfunctional mitochondria, generation of reactive oxygen species with down-regulation or consumption of antioxidants causing oxidative stress and lipid peroxidation, increased activity of cytochrome P450 2E1, disturbed production of adipocytokines, and the effects of gut-derived cytotoxic products. The dynamic interplay of these processes in the pathogenesis of NAFLD remains incompletely understood and is an area of active research.

This book provides a comprehensive review of the studies concerning HBV epidemiology, pathogenesis and treatment. In addition, it describes recent advances in the knowledge of immune response function, promoting either viral control or persistence, and effects of antiviral therapy in patients with HBV acute or chronic infection are reported. Although mechanisms involved in inflammatory and immune response in acute and chronic HBV infections have been extensively studied, several questions remain unresolved. Moreover, in recent years several key steps in research have contributed to improve our present knowledge of immunopathogenesis of HBV infection.

Hepatitis B virus (HBV), discovered in 1966, infects more than 350 million people in the world. The infection of HBV is a leading cause of chronic carriage of the virus and progressive liver diseases, such as hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). HBV consists of a circular, partially double-stranded DNA molecule of 3.2 kb in length, which contains four overlapping reading frames that code for surface proteins (HBsAg), core proteins (HBcAg/HBeAg), the viral polymerase, and the transcriptional transactivator X protein. Chronic hepatitis appears to be due to a suboptimal cellular immune response that destroys some of the infected hepatocytes and does not purge the virus from the remaining infected hepatocytes, thereby permitting the persisting virus to trigger a chronic indolent necroinflammatory liver disease that sets the stage for development of HCC. However, the mechanisms responsible for malignant transformation in chronic HBV infection are not well defined, and both viral and host factors have been implicated in the process. All cases of HCC occur after many years of chronic hepatitis which could, theoretically, provide the mitogenic and mutagenic environment to precipitate random genetic and chromosomal damage, and lead to the development of HCC. Hepatitis B virus X protein (HBx), an important transforming inducer, plays a crucial role in HCC development. HBx has the capability to influence a variety of signal transduction pathways within the cells. Monitoring of the HBV genotypes and antibody to Hepatitis B x antigen (anti-HBx) are significant for predicting early diagnosis of liver cirrhosis and HCC. HBV and Hepatitis C virus or HIV coinfections can accelerate the course of chronic liver disease and facilitate progression to cirrhosis and HCC. As for therapy of liver diseases, five drugs are now FDA-approved for the treatment of HBV, including interferon (IFN), lamivudine, adefovir, entecavir, and peginterferon alfa-2a. Moreover, the prevention for HBV infection is very important. It is likely that the most important outcome of the research on HBV has been the invention, development, and application of the vaccine against HBV. However, at present most investigators focus on basic research rather than practical applications. The HBV research should be focused on animal models and clinical practice. The technology update in HBV research and the multisubject combination may be attached importance to next a few decades. Some molecular approaches, such as antisense, oligonucleotides, ribozymes, RNA interference targeting HBV mRNA, are available in antiviral therapies.

Liver transplantations require a complex and varied, multidisciplinary approach involving not only hepatologists and surgeons but also pathologists, psychologists, professional educators, nurses and, in the case of young patients, also pediatricians and development experts. This textbook provides an overview of the management problems involved in liver transplantation for acute and chronic liver disease, pediatric liver transplantation and the psychosocial aspects of liver transplantation. A closing chapter, focusing on the developments and future prospects in liver transplantation, outlines the potential offered by donors after cardiac death, cell therapies and organogenesis. The multidisciplinary approach is also maintained in the selection of authors, all experts actively engaged in the various disciplines involved in liver transplantations. This aspect, together with its precise and didactic descriptions of all phases of liver transplantation for chronic and acute diseases - from managing waiting lists to post-transplant complications - make the book a valuable tool for fellows, trainees, and specialists in the field seeking accurate framework for liver transplantation in its many facets.

The liver is a large organ that sits in the right upper abdomen, just under the right lung. It is one of the body's most "intelligent" organs in that it performs so many different functions at the same time. The liver makes proteins, eliminates waste material from the body, produces cholesterol, stores and releases glucose energy and metabolises many drugs used in medicine. It also produces bile that flows through bile ducts into the intestine where it helps to digest food. This organ also has the ability to regenerate itself if it is injured or partially removed. Cirrhosis is scarring of the liver that involves the formation of fibrous (scar) tissue associated with the destruction of the normal architecture of the organ. Many types of chronic injury to the liver can result in scar tissue. This scarring distorts the normal structure and re-growth of liver cells. The flow of blood through the liver from the intestine is blocked and the work done by the liver, such as processing drugs or producing proteins, is hindered. Until recently, the most common cause of cirrhosis of the liver in the United States was attributed to alcohol abuse. Because of the rapid increase of hepatitis C virus infection, hepatitis C has now taken over first place (26%), with alcohol abuse falling to second place, but only slightly behind at 21%. This outstanding book elucidates new and important research results from throughout the world.

The liver is a large organ that sits in the right upper abdomen, just under the right lung. It is one of the body's most 'intelligent' organs in that it performs so many different functions at the same time. The liver makes proteins, eliminates waste material from the body, produces cholesterol, stores and releases glucose energy and metabolises many drugs used in medicine. It also produces bile that flows through bile ducts into the intestine where it helps to digest food. This organ also has the ability to regenerate itself if it is injured or partially removed. Cirrhosis is scarring of the liver that involves the formation of fibrous (scar) tissue associated with the destruction of the normal architecture of the organ. Many types of chronic injury to the liver can result in scar tissue. This scarring distorts the normal structure and re-growth of liver cells. The flow of blood through the liver from the intestine is blocked and the work done by the liver, such as processing drugs or producing proteins, is hindered. Until recently, the most common cause of cirrhosis of the liver in the United States was attributed to alcohol abuse. Because of the rapid increase of hepatitis C virus infection, hepatitis C has now taken over first place (26%), with alcohol abuse falling to second place, but only slightly behind at 21%. This outstanding new book elucidates new and important research results from throughout the world.

Advances in our knowledge of the pathogenesis and management of portal hypertension and its complications over the last 2 decades have been astronomical. However, most of the management strategies remain palliative and serves as a bridge to liver transplantation. Despite the availability of a number of books in the field of hepatology, portal hypertension as the main life-threatening complication needs a dedicated book to link between recent advances in research and current clinical practice. This book includes dedicated chapters on gastric varices management, ectopic varices management, sinusoidal obstruction syndrome, portal hypertensive bilopathy, portal hypertension as a risk factor in nonhepatic abdominal surgery, idiopathic portal hypertension, and portal hypertension in pregnancy. As all other chapters, they represent updates on the recent advances and were written by well-known experts in such areas. It also includes a self-assessment section for evaluation of the level benefit obtained from reading this book. Many illustrations, tables, lists, algorithms, figures, and colour plates are included to serve the educational purpose of this book.

The liver is a large organ that sits in the right upper abdomen, just under the right lung. It is one of the body's most "intelligent" organs in that it performs so many different functions at the same time. The liver makes proteins, eliminates waste material from the body, produces cholesterol, stores and releases glucose energy and metabolises many drugs used in medicine. It also produces bile that flows through bile ducts into the intestine where it helps to digest food. This organ also has the ability to regenerate itself if it is injured or partially removed. Cirrhosis is scarring of the liver that involves the formation of fibrous (scar) tissue associated with the destruction of the normal architecture of the organ. Many types of chronic injury to the liver can result in scar tissue. This scarring distorts the normal structure and re-growth of liver cells. The flow of blood through the liver from the intestine is blocked and the work done by the liver, such as processing drugs or producing proteins, is hindered. Until recently, the most common cause of cirrhosis of the liver in the United States was attributed to alcohol abuse. Because of the rapid increase of hepatitis C virus infection, hepatitis C has now taken over first place (26%), with alcohol abuse falling to second place, but only slightly behind at 21%. This outstanding book elucidates new and important research results from throughout the world.

This book focuses on the critical care of the patient with acute, acute on chronic and chronic liver failure as well as the peri-operative care of the patient with liver transplantation. Each of these disease processes is unique in pathophysiological manifestations, underpinnings of physiology and treatment options. Patients with acute, chronic or acute on chronic liver failure are a growing fraction of ICU admissions. Hepatic Critical Care serves as the essential reference for both practicing intensivists at community hospitals and tertiary referral centers. This textbook is also targeted towards trainees specifically interested in taking care of patients with liver disease and liver transplantation.

This book focuses on patients with end-stage-liver disease (ESLD) who could possibly qualify for liver transplant. This patient cohort raises many problems: who should be treated and also, when is it too late for transplant? The authors are all dedicated experts in the field of ESLD/liver transplantation, but from different disciplines with different views of the problem. In the past 15 years many things have changed in the treatment for these patients: cardiac assessment, treatment of porto-pulmonary hypertension, hemodynamics, coagulation assessment and management, diagnosis of kidney failure, and the timing of dialysis. These issues are comprehensively discussed in this book, in order to provide physicians starting in the field of transplantation an overview of different areas of concern. This book is aimed at specialists and trainees in critical care, hepatology, anesthesia, surgery, and nephrology.

The incidence of primary and metastatic liver tumors is rising and the therapeutic armamentarium for these tumors is expanding at a rapid pace. Surgery remains the primary treatment modality for these tumors. With improvements in our perioperative management and operative techniques a larger proportion of patients are able to undergo potentially curative liver surgery. In addition, indications and criteria for liver transplantation for both primary and metastatic liver tumors are constantly expanding. Unfortunately, many patients are not amendable to surgical resection or liver transplantation and therefore alternative liver-directed therapies are routinely being implemented as part of complex multidisciplinary treatment models. However, these models are continually evolving as these regional therapeutic options continue to expand. New embolization agents and techniques, as well as, improvements in radiation delivery, are all evolving in the background of improvement in systemic and targeted therapy options for these tumors. This book provides a comprehensive, state-of-the art review of the current state of liver-directed therapy for malignant liver tumors. The book will serve as a valuable resource for not only surgeons and clinicians but for researchers with an interest in malignant liver tumors. The book focuses on the therapeutic approach to primary and metastatic tumors providing an up-to-date review on surgical liver anatomy and new imaging techniques as well as patient selection and technical consideration for resection and transplantation. In addition, the book provides new insight into novel and evolving therapies in the areas of transarterial therapy such as: (i) bland embolization, (ii) chemoembolization, and (iii) radioembolization; as well as new radiation techniques including SBRT and proton therapy. Furthermore, the expanding role of hepatic artery infusion therapy in primary malignant tumors is highlighted. Finally, integration of all these regional therapy options with upcoming and evolving systemic and targeted therapy regimens are integrated and discussed. This book will serve as a very useful resource for clinicians and researchers managing and treating patients with these challenging malignancies. It provides 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.

This volume covers a state-of-the-art illustration of recent discoveries concerning obesity-related fatty liver diseases and liver cancer. The contents are extensive and comprehensive. It brings important topics in the field all together under one umbrella, from epidemiology and etiology, molecular pathogenesis, cellular biology, epigenetics, immunology, microbiology, animal models to therapeutic approaches and treatments. All the book contributors are leading experts in the field. It will appeal to researchers, clinicians and graduate students in obesity, fatty liver diseases, GI/Liver cancer field. It may also yield benefits for pharmaceutical companies with regard to drug discovery.

This volume provides a comprehensive introduction and review of small bowel capsule endoscopy (SBCE). The book reviews the data regarding appropriate indications and contraindications for the implementation of small bowel capsule endoscopy, while discussing in detail the evolving role of SBCE in the treatment of obscure gastrointestinal bleeding, and the management of inflammatory bowel disease, small bowel polyposis syndromes, and refractory malabsorption. Topics such as complications of SBCE, methods to perform SBCE on patients with dysphagia or gastric emptying pathology, and understanding the normal anatomy of the gastrointestinal tract when viewed via SBCE are also discussed. In addition, an introduction to colon capsule technology and the next generation of small bowel capsule imaging is reviewed. The text is complemented by several illustrative cases that are demonstrated with both online full length videos as well as an online interactive companion that includes review questions to reinforce concepts learned in the text. Written by experts in the field, Capsule Endoscopy: A Guide to Becoming an Efficient and Effective Reader is an invaluable resource for novice capsule endoscopy readers, fellows in gastroenterology and hepatology, researchers, mid-level providers, residents, and medical students with an interest in learning how to implement and perform SBCE in the investigation of small bowel diseases.

This book addresses the current understanding of the diagnosis and management of biliary disease across all ages, with emphasis on how the latest advances in clinical science may be integrated into current and future therapies. The coverage is wide ranging, encompassing congenital and acquired conditions including cholestatic syndromes, biliary atresia, drug-induced cholestasis, primary biliary cholangitis/cirrhosis, primary sclerosing cholangitis, cholangiocarcinoma, gallstone disease, and autoimmune sclerosing cholangitis. With contributions from basic and clinical scientists, the relevance of state-of-the-art mechanistic biology to diagnosis, treatment, and future opportunities for drug design is clearly explained. The balance between science and clinical practice will ensure that this book makes a lasting contribution to the field. A broad readership will find the book easy to access and a rich source of information on current best practice and evolving management strategies.

Primary liver cancer is the third most deadly and fifth most common cancer worldwide (approximately 500,000 deaths annually), with a sharp increase of incidence in the United States in recent years. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major types of primary liver cancer. Risk factors include gender, hepatitis B virus (HBV), hepatitis C virus (HCV), cirrhosis, metabolism diseases, diabetes, obesity, toxins, excess alcohol consumption and smoking. Liver cancer arises most frequently in inflammatory livers with extensive oxidative stress due to viral hepatitis which causes over 80 per cent of HCC cases worldwide. Currently, survival remains dismal for most HCC and CC patients, largely due to the tumor's aggressiveness at the time of diagnosis and the lack of effective therapy.

This atlas describes and illustrates in detail the surgical procedures employed in laparoscopic anatomical liver resection, according to tumor location. The surgical approach and techniques are explained for each type of laparoscopic liver resection based on the involved anatomical segment, section, and hemi-liver. Attention is also drawn to potential complications and the means of preventing and managing them. Beyond anatomical liver resection, guidance is provided on non-anatomical resections that do not pay regard to segmental, sectional, or lobar anatomy. The coverage is completed by the inclusion of useful information on instruments and energy devices as well as the basic skills required for laparoscopic liver resection. In presenting a clear practical approach to each laparoscopic anatomical major and minor resection, the Color Atlas of Laparoscopic Liver Resection will be an invaluable guide for trainees. In addition, it will equip more experienced surgeons with much useful information that will enable them to further improve their technique.

The new edition of this pocket guide has been fully updated to cover the common manifestations of liver disease, how to treat them and when to refer patients on to specialist centers. New chapters on Acute Liver Failure, Nutrition and Congenital Heart Disease have been added to reflect the key issues in management of liver diseases. The book outlines the common clinical liver diseases such as fatty liver disease and viral hepatitis, among others, and their current up to date management. Written by experts in the field and containing figures and tables, as well as case histories and questions, this is an enjoyable and reader-friendly book for the busy physician. With its authoritative, didactic style and short chapters, it covers the common presentations and complications of liver disease, and how to deal with them. Given the increasing prevalence of liver disease in the UK and Worldwide, this is an ideal reference book for primary care physicians, doctors in specialist training, clinical nurse specialists and for gastroenterologists, who see patients with liver disease in their working lives.

Liver disease has been identified as a leading cause of death in HIV-infected patients since the introduction of highly active antiretroviral therapy (HAART) in 1996. The HIV treatment community has been caught largely unaware of this emerging dilemma. Many HIV care providers are ill-equipped to understand and interpret liver injury patterns, or to provide comprehensive care and management for viral coinfections which they are not familiar with. HIV and Liver Disease provides a comprehensive update of the field covering the epidemiology, pathogenesis, management and treatment of liver disease in patients with HIV infection. The volume will help HIV care providers understand and interpret liver injury patterns, and/or provide comprehensive care and management for viral coinfections. Gastroenterologists and hepatologists will gain an understanding of complex drug regimens that are used to treat HIV and which may impact HCV and HBV treatment. Written by expert clinicians and researchers across multiple disciplines, HIV and Liver Disease will be of great value to gastroenterologists, hepatologists, infectious disease practitioners, as well as other health care providers who provide care or participate in research in the field of HIV.

This book provides a comprehensive overview of the diagnosis and management of diseases of the biliary tree. Topics covered include: congenital biliary abnormalities, genetic cholangiopathies, autoimmune cholangiopathies, inflammatory and drug-related cholangiopathies, and cholangiocarcinoma. Given their particular importance (even for clinicians working with adults), pediatric conditions are also examined. In addition, a special section is devoted to pregnancy and diseases of the biliary tree, and to transplants and diseases of the biliary tree. Each chapter offers up-to-date information on the management of the diseases discussed. Moreover, the book addresses new treatments for autoimmune cholestatic liver diseases, reflecting the new therapeutic targets that have recently been discovered. Examples include farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-agonists, together with new drugs that affect the composition of bile flow. Given its scope, the book offers a valuable guide for a broad range of practitioners.