This volume is the first text to concisely yet comprehensively cover developments for both alcoholic and nonalcoholic fatty liver disease in an organized fashion. Aspects of these two diseases covered in the book include global epidemiology and risk factors, pathogenesis, animal models, hepatic and extra-hepatic malignancies, treatment models, and current and emerging therapies. Written by experts in the field, Alcoholic and Non-Alcoholic Fatty Liver Disease: Bench to Bedside is a valuable resource for gastroenterologists, pathologists, and hepatologists who treat patients with alcoholic and nonalcoholic fatty liver disease.

This book is a printed edition of the Special Issue "Non-Alcoholic Fatty Liver Disease Research 2016" that was published in IJMS

This new book entitled "Non-Alcoholic Fatty Liver Disease Research 2016" covers a selection of recent research topics and current review articles in the field of nonalcoholic fatty liver disease (NAFLD) that have been recently published in a monographic Special Issue of the International Journal of Molecular Sciences (IJMS) journal. false,NAFLD is an "umbrella" definition that encompasses a spectrum of histopathological liver changes ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with/without fibrosis, "cryptogenic" cirrhosis and hepatocellular carcinoma. false,NAFLD has become one of the most common forms of chronic liver disease worldwide and its prevalence is expected to continue rising. false,It is now becoming increasingly clear that the clinical and economic burden of NAFLD does not only affect the liver, but also affects the risk of developing cardiovascular disease, type 2 diabetes mellitus, colo-rectal neoplasms, chronic kidney disease and other extra-hepatic diseases that have a considerable impact on health-care expenditures. false,Against this background, further research is needed to better understand the natural history, and the molecular pathogenesis of NAFLD, as well as to elucidate the underlying mechanisms by which NAFLD contributes to the increased cardiometabolic risk, and to disclose novel and effective treatment strategies for this increasingly prevalent and burdensome disease.false,Some of the leading international researchers in this area expressed a willingness to contribute to this book providing an updated, state-of-the-art view on the aforementioned topics, and also suggesting novel research avenues for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a major medical challenge because of its increasing prevalence, difficulties in diagnosis, complex pathogenesis, and lack of approved therapies. In the near future, it will become the major form of chronic liver disease in adults and children and the leading indication for liver transplantation. It can be detected by noninvasive and invasive tools, and its treatment depends mainly on lifestyle modification to prevent disease progression and its related sequelae. This book provides information on NAFLD prevalence, etiology, pathogenesis, pathology, diagnosis, and treatment. Chapters cover such topics as experimental work related to the disease, other diseases related to NAFLD, and noninvasive tools for diagnosis.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population and is commonly recognized as the hepatic manifestation of the metabolic syndrome. The histological spectrum of NAFLD ranges from isolated steatosis to non-alcoholic steatohepatitis (NASH), with risk of developing fibrosis and subsequent cirrhosis and hepatocellular carcinoma. The gold standard for diagnosing NAFLD is liver biopsy. However, because of its invasive nature, several non-invasive methods have been developed and validated in evaluating fat and fibrosis in patients with NAFLD. Liver fat content can be assessed using various methods. The conventional histopathological method consists of a visual semiquantitative approach in which the pathologist uses a four-point scale: grade 0 corresponds to fat deposition in <5% of hepatocytes and grade 1?3 (which is needed for the diagnosis of NAFLD) corresponds to ?5%. An alternate approach is to quantitatively assess steatosis using stereological point counting (SPC) – which rely on liver biopsy. However, in vivo proton magnetic resonance spectroscopy (1H-MRS) is a reliable noninvasive method that can be used to quantitatively assess total hepatic lipid content, or proton density fat fraction (PDFF). In Paper I we compared the conventional semiquantitative histological method (grade 0-3) with SPC and 1H-MRS. We found a strong positive correlation between 1H-MRS and SPC, whereas the correlations between 1H-MRS or SPC and histopathological grading were substantially weaker. Using the widely used cut-off value of PDFF ?5%, all participants were found to have steatosis (specificity 100%, sensitivity 53%). Reducing the cut-off value to 3% maintained 100% specificity while increasing sensitivity to 79%. In Paper IV we evaluated quantitative steatosis, by SPC, in 106 biopsy-proven NAFLD patients during a 20-year follow-up. SPC was independently associated with an increased risk of all-cause mortality and development of T2DM. Moreover, in the 59 patients with sequential biopsies (approximately 10 years apart), a reduction of quantitative hepatic steatosis decreased the all-time risk of developing T2DM. NASH is commonly seen as a histological feature portending a worse prognosis in NAFLD. Interestingly, no dual biopsy study has ever shown that NASH predicts fibrosis progression. Yet, NASH is seen as a surrogate marker in pharmaceutical trials – were resolution in NASH is equivalent to future resolution of fibrosis. In Paper II we conducted a long-term follow-up study (20 years) in a large cohort of biopsy-proven NAFLD patients (n=646), in a collaboration with Karolinska Institute. We could not ascertain that NASH had any effect on all-cause, or disease-specific mortality. However, higher stages of fibrosis predicted all-cause and disease specific mortality. In Paper III, we present 129 biopsy-proven NAFLD patients, in which we had prospective, longitudinal data. They were included between 1988 and 1993. All patients alive, were re-invited 2003-2005 and 2013-2015. Dual biopsies were present in 68 patients, and three consecutive biopsies were available in 33 patients. Results showed that NAFLD is a highly heterogeneous disease, with 9.3% developing end-stage liver disease and 16% progressing to advanced stages of fibrosis without any clinically significant baseline data predicting disease progression. In summary, when using 1H-MRS as a diagnostic method for NAFLD, the diagnostic cut-off should be reduced from 5% to 3%. Furthermore, quantitative amount of hepatic steatosis could be used to stratify patients with NAFLD related to future risk of developing T2DM. Moreover, we have shown that NASH does not predict future all-cause or disease-specific mortality nor end-stage liver disease, therefore a different surrogate marker should be used in clinical trials when assessing NAFLD improvement, so to not imbue false reliance in new therapies. Lastly, we have shown that NAFLD has a more dismal prognosis than previously reported, and that it is unexpectedly difficult to predict fibrosis progression in individual NAFLD patients, emphasizing the need for robust non-invasive biomarkers suitable to monitor large number of patients.

Nonalcoholic fatty liver disease (NAFLD) is known as the hepatic manifestation of the metabolic syndrome, and while most patients develop simple steatosis, up to one-third can develop nonalcoholic steatohepatitis (NASH). NASH is a chronic inflammatory condition of the liver that can further progress to fibrosis and cirrhosis, which may eventually lead to liver failure and death. While we have increased our mechanistic knowledge regarding the pathogenesis of NASH within the last decade, treatment options are still limited and liver biopsies have remained the gold standard for diagnosis. To achieve major clinical breakthroughs for NASH patients, it is not sufficient to use a single animal model, since each model has specific limitations. Furthermore, we should rely more on alternative models such as organ-on-a-chip, which will enable us to explore unknown aspects of disease pathogenesis much faster and serve as clinically relevant surrogates for murine models. Another important direction for the improvement of patient health is to pay more attention to extrahepatic, organ-specific and systemic effects, which are associated with NASH. The articles in this Special Issue include an up-to-date overview of the rapidly developing technologies, novel targets for intervention and insights in the field in NASH. Additionally, these articles describe the major challenges in the field, strategies to overcome them and suggestions for future directions. To improve patient's outcome, clinicians, as well as scientists with biomedical, nutrition, physics and mathematics backgrounds, should join forces. Although challenges remain, the future of the field seems promising as these novel technologies and developments are expected to lead to progress in NASH.

Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.

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.

Nonalcoholic fatty liver disease (NAFLD) with a prevalence of 20-30% worldwide is characterized by the buildup of fat in the liver (liver steatosis) with no or little alcohol consumption. Its principal causes are modern diet and occidental lifestyle. It is characterized by metabolic disturbances such as insulin resistance, inflammation, and oxidative stress, considered as the hepatic manifestation of metabolic syndrome. There is no effective drug therapy for this disease; therefore, lifestyle interventions remain as the first-line treatment. Nevertheless, the adherence rates to this type of treatment are very low, so great efforts are focused at finding novel therapeutic agents for the prevention of hepatic steatosis and its progression. This book presents a systematic and comprehensive revision about NAFLD, highlighting its epidemiological and molecular aspects, as well as its prevention and treatment.