Obesity, Fatty Liver and Liver Cancer PDF
Preview Obesity, Fatty Liver and Liver Cancer
Advances in Experimental Medicine and Biology 1061 Jun Yu Editor Obesity, Fatty Liver and Liver Cancer Advances in Experimental Medicine and Biology Volume 1061 Editorial Board: IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA RODOLFO PAOLETTI, University of Milan, Milan, Italy NIMA REZAEI, Tehran University of Medical Sciences Children’s Medical Center, Children’s Medical Center Hospital, Tehran, Iran More information about this series at http://www.springer.com/series/5584 Jun Yu Editor Obesity, Fatty Liver and Liver Cancer Editor Jun Yu Institute of Digestive Disease and Department of Medicine & Therapeutics State Key Laboratory of Digestive Disease LKS Institute of Health Sciences The Chinese University of Hong Kong Hong Kong, Hong Kong ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-981-10-8683-0 ISBN 978-981-10-8684-7 (eBook) https://doi.org/10.1007/978-981-10-8684-7 Library of Congress Control Number: 2018943896 © Springer Nature Singapore Pte Ltd. 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Foreword Obesity has become a prevalent disorder due to various factors such as opu- lent meals, unhealthy eating habits and sedentary lifestyle. More than two- thirds of the adult population in developed countries is considered overweight and more than a third of them are obese. In addition to the well-known asso- ciation of obesity with type II diabetes and cardiovascular diseases, emerging evidence suggests that obesity represents a major risk factor for fatty liver diseases, hepatocellular carcinoma (HCC) and other solid tumours. Non- alcoholic fatty liver disease (NAFLD) is becoming the most common cause of chronic liver disease in the West and in Asia. Its incidence in obese indi- viduals can be extremely high. NAFLD can progress from relatively benign, simple steatosis to more aggressive diseases such as non-alcoholic steato- hepatitis (NASH) and HCC. Given that obesity, fatty liver and fatty liver- associated HCC are increasingly prevalent in developed countries and in particular in children, this book is an important endeavour. It offers a compre- hensive overview on these diseases and provides an outlook on future strate- gies for their detection, prevention and treatment. The purpose of this book is to provide both medical professionals and research scientists with an expert update on NAFLD, NASH and fatty liver disease-associated HCC. In particular, it focusses on the recent advances as well as unresolved challenges in the field of fatty liver research. The book begins with the description of the epidemiology and etiology of NAFLD and associated HCC, and highlights their rising trend in the developed countries. The role of inflammation in the pathogenesis of NAFLD and HCC is explored in the subsequent chapters because accumulating evidence suggests that inflammation is a key for the transition from simple steatosis to NASH and fibrosis. Immune mediators, such as cytokines, adipokines and chemokines, play a pivotal role in the development of NAFLD and NASH. In these chap- ters, the underlying molecular mechanisms and the potential of the immune system in the pathogenesis of NAFLD are being discussed. Furthermore, the authors elucidate the pathogenesis of NAFLD-related HCC and the underly- ing role of the metabolic syndrome. Recent advances in the utilization of clinical and genetic biomarkers for patient stratification and disease detection are summarized. Gut microbiota disorder has been established recently as a novel contribu- tor to obesity and liver cancer. In addition to outlining the influence of gut microbiota-derived metabolites on the pathogenesis of NAFLD, this book illustrates the interaction between obesity and microbiota, as well as its v vi Foreword contribution to the development of NAFLD. Microbiota dysfunction in HCC is then discussed, highlighting its potential role in the transition from NAFLD to HCC. The last part of the book focuses on established therapies and future therapeutic strategies for the prevention and treatment of NAFLD, NASH and HCC, respectively. In this up-to-date book, researchers and clinicians from different regions share their expertise in NAFLD, NASH and NASH-associated HCC. Supported by clinical studies and experimental data, the authors’ insights into current challenges and future perspectives will help shed light on the development in the field. The authors and the editor are to be congratulated for their work. This book does enrich our knowledge on fatty liver diseases. Alexander L. Gerbes Dr. Alexander L. Gerbes is a Professor of Internal Medicine in Medizinische Klinik und Poliklinik II, Klinikum der Universität München, FRG. He earned his MD degree following study at University of Munich, UCSF at San Francisco and the Royal Hallamshire Hospital, Sheffield, UK, from the Ludwig-Maximilians-University Munich in 1981. He began his professional career as staff physician at the Department of Medicine, University of Munich where he was appointed as assistant professor in 1990. Following a research stay at University of Montreal, Canada, 1991–1992, he was granted lifetime full professorship (C3) in 1995. In 2001, he was appointed as deputy chief of the Department of Medicine 2 of the Munich University Hospital where he founded the Liver Center Munich in 2008. Currently, he is acting chief of the Department of Gastroenterology and Hepatology at the Munich university hospital and is medical director of the Munich liver transplantation program. From the start of his academic career, Alexander Gerbes has focused his research on patho- physiology, diagnosis and treatment of liver diseases with emphasis on com- plications of cirrhosis. He is a Fellow of the European Board of Gastroenterology, Fellow of the AGA and Inaugural Fellow of AASLD. Since 2010, he has served as deputy editor of GUT, a leading journal of gastroen- terology and hepatology. He has co-authored over 200 articles in acknowl- edged journals including N Engl J Med, Lancet, Gastroenterology, Gut, Hepatology and J Hepatol. Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Chi Chun Wong and Jun Yu 2 Epidemiology and Etiologic Associations of Non-alcoholic Fatty Liver Disease and Associated HCC . . . . . . . . . . . . . . . . . . 3 Ken Liu and Geoffrey W. McCaughan 3 Pathogenesis of NASH: How Metabolic Complications of Overnutrition Favour Lipotoxicity and Pro-Inflammatory Fatty Liver Disease . . . . . . . . . . . . . . . . 19 Geoffrey C. Farrell, Fahrettin Haczeyni, and Shivakumar Chitturi 4 Chemokines and Chemokine Receptors in the Development of NAFLD. . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Yoon-Seok Roh and Ekihiro Seki 5 NAFLD Related-HCC: The Relationship with Metabolic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Xiang Zhang 6 Hepatocellular Carcinoma in Obesity: Finding a Needle in the Haystack? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 György Baffy 7 Dysregulated Epigenetic Modifications in the Pathogenesis of NAFLD-HCC . . . . . . . . . . . . . . . . . . . . . . 79 Fung Zhao 8 The Influence of Gut Microbial Metabolism on the Development and Progression of Non-alcoholic Fatty Liver Disease . . . . . . . . . . . . . . . . . . . . . . 95 Wei Jia and Cynthia Rajani 9 Microbiota, Obesity and NAFLD . . . . . . . . . . . . . . . . . . . . . . . . 111 Louis H. S. Lau and Sunny H. Wong vii viii Contents 10 Autophagy, NAFLD and NAFLD- Related HCC . . . . . . . . . . . . 127 William K. K. Wu, Lin Zhang, and Matthew T. V. Chan 11 Animal Models of Non-alcoholic Fatty Liver Diseases and Its Associated Liver Cancer . . . . . . . . . . . . . . . . . . . . . . . . . 139 Jennie Ka Ching Lau, Xiang Zhang, and Jun Yu 12 Current Prevention and Treatment Options for NAFLD . . . . . 149 Vincent Wai-Sun Wong Contributors György Baffy Department of Medicine, VA Boston Healthcare System and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Matthew T. V. Chan Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong Shivakumar Chitturi Australian National University Medical School, and Gastroenterology and Hepatology Unit, The Canberra Hospital, Woden, ACT, Australia Geoffrey C. Farrell Australian National University Medical School, and Gastroenterology and Hepatology Unit, The Canberra Hospital, Woden, ACT, Australia Fahrettin Haczeyni Australian National University Medical School, and Gastroenterology and Hepatology Unit, The Canberra Hospital, Woden, ACT, Australia Wei Jia University of Hawaii Cancer Center, Honolulu, HI, USA Shanghai Jiao Tong University School of Medicine, Shanghai, China Jennie Ka Ching Lau Institute of Digestive Disease and Department of Medicine & Therapeutics, State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SHHO College, The Chinese University of Hong Kong, Hong Kong, Hong Kong Louis H. S. Lau Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Department of Medicine & Therapeutics and LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong Ken Liu AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia Faculty of Medicine, University of Sydney, Sydney, NSW, Australia Centenary Institute, University of Sydney, Sydney, NSW, Australia ix
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