Table Of ContentAdvances 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
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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
