Non-Alcoholic Fatty Liver Disease

Geoff Farrell, Professor of Hepatic Medicine, Director of Gastroenterology, The Canberra Hospital, Australia Geoffrey Farrell graduated MB BS from the University of Tasmania in 1970, and trained in gastroenterology and hepatology at the Royal Prince Alfred and Royal Brisbane Hospitals, the latter with Lawrie Powell with whom he completed an MD on hepatic drug metabolism. He was awarded an NHMRC CJ Martin Fellowship to conduct post-doctoral research in UCSF, and in 1980 returned to Sydney to establish a Liver Research Group at Westmead Hospital. He was promoted to a personal chair in 1993, then accepted the Storr Chair in Hepatic Medicine. He remained Director of the Storr Liver Unit until Jan 2006, when he accepted the position as Professor of Hepatic Medicine with ANU Medical School and Director of Gastroenterology and Hepatology at The Canberra Hospital. He has held many leadership roles in medical research, gastroenterology, editorial boards, and academic medicine, including Editor-in-Chief of Journal of Gastroenterology and Hepatology since November 2006. Geoff Farrell's research interests are in non-alcoholic steatohepatitis, viral hepatitis, drug-induced liver injury, and liver regeneration. He has published 3 books, including the first on non-alcoholic fatty liver disease, and written more than 180 scientific papers and 100 reviews/chapters and editorials in the fields of hepatology and biochemical pharmacology. His work is very highly cited, with an H-index of 50, more than 20 articles cited >100 times, average citation 32 per paper, and 15 articles being the subject of editorials in major medical journals. He is CIA on an NHMRC Program Grant to study the molecular and cellular basis of liver disease, and has recently held a Centre for Clinical Research Excellence Program grant to improve outcomes for patients with liver disease. Arthur McCullough, Department Chair of Gastroenterology and Hepatology, Cleveland Clinic, USA Arthur McCullough, MD, is Department Chair of Gastroenterology and Hepatology and a Staff Physician in the Department of Pathobiology and Transplantation Center at Cleveland Clinic. He was appointed in 2006. He attended medical school at SUNY Health Science Center at University Hospital of Syracuse, N.Y. He completed his internship and residency at Cleveland Clinic and a fellowship at Mayo Clinic in Rochester, Minn. He is one of the most senior hepatologists in the United States and is the current President of the American Association for the Study of Liver Diseases. Other significant achievements are: Best Doctor's in America: "Midwest Region" annually from 1996-2008; Chair of the NIH-funded Clinical Research Network on Fatty Liver Disease (federal funding); NIH Grant on Omega 3 Fatty Acids in Diabetes (federal funding); New Novel Agents for Hepatitis C Patients who failed to respond to previous therapy (non-federal funding) Christopher Day, Pro-Vice-Chancellor for the Faculty of Medical Sciences, Professor of Liver Medicine and Consultant Hepatologist, School of Clinical Medical Sciences, Newcastle University, UK Chris Day qualified from Cambridge University in 1983 and subsequently trained in General Medicine and Hepatology at Newcastle, becoming Consultant Hepatologist in the Liver Unit at Newcastle's Freeman Hospital in 1994 and Professor of Liver Medicine at University of Newcastle University in 2000. He was formerly Head of the School of Clinical Medical Sciences at the University and since April 2008 has been Pro-Vice-Chancellor of the Faculty of Medical Sciences. Professor Day's research interests focus largely on fatty liver disease related both to obesity and to alcohol, with additional interests in drug-induced liver injury and liver fibrosis. His work has been funded by the MRC and the Wellcome Trust and he is a former MRC Clinical Training Fellow and Clinician Scientist Fellow. In 1999 he was the Goulstonian Lecturer of the Royal College of Physicians and in 2000 was awarded the research gold medal of the British Society of Gastroenterology. He is a Fellow and Councillor of the Academy of Medical Sciences, an Executive Member of the Medical Schools Council and an NIHR Senior Investigator. He is also Chief Editor of the Journal of Hepatology, and is on both the Populations and Systems Medicine Board and the Translational Stem Cell Research Committee of the Medical Research Council.

List of Contributors, vii

1 What is non-alcoholic fatty liver disease (NAFLD), and why is it important? 1
Geoffrey C. Farrell, Arthur J. McCullough, and Christopher P. Day

2 NAFLD in the community, 17
Leon A. Adams


3 Pathology of NAFLD, 27
Elizabeth M. Brunt and David E. Kleiner

4 The natural history of NAFLD, 37
Paul Angulo

5 Emerging concepts on the pathogenesis of non-alcoholic steatohepatitis (NASH), 46
Isabelle A. Leclercq

6 Diabetes and NAFLD: why is the connection important? 62
Elisabetta Bugianesi

7 NAFLD and cardiovascular risk factors: implications for vascular disease, 71
Giovanni Targher

8 A primary care perspective of fatty liver: diagnosis, management, prescribing, and when to refer, 84
Shivakumar Chitturi and Geoffrey C. Farrell

9 Imaging of NAFLD, 93
Takeshi Yokoo, An Tang, and Claude B. Sirlin

10 Non-invasive methods to determine the severity of NAFLD and NASH, 112
Vincent Wai-Sun Wong and Henry Lik-Yuen Chan

11 Fatigue, quality of life, and psychosocial issues for people with NAFLD, 122
Julia L. Newton and James Frith

12 Physical activity and cardiovascular fi tness in patients with NAFLD: clinical importance and therapeutic implications, 132
Ingrid J. Hickman, Graeme A. Macdonald, and Nuala M. Byrne

13 NAFLD, obesity, and bariatric surgery, 149
Philippe Mathurin

14 Genetic predisposition to NAFLD and NASH: implications for pathogenesis, diagnosis, prevention, and management, 157
Quentin M. Anstee, Ann K. Daly, and Christopher P. Day

15 NAFLD in children, 171
Ariel E. Feldstein

16 The pointy end of the NAFLD iceberg: cirrhosis, portal hypertension, and liver failure, 182
Jonathon W. Schwake, Dawn M. Torres, and Stephen A. Harrison

17 Non-alcoholic fatty liver disease, hepatocellular cancer, and other cancers, 192
Janine Graham and Helen L. Reeves

18 NAFLD in Chinese and South Asian people, 206
Jia-Horng Kao, Deepak Amarapurkar, and Jian-Gao Fan

19 Non-alcoholic fatty liver disease in Japan, 217
Takeshi Okanoue, Kohichiroh Yasui, and Yoshito Itoh

20 Non-alcoholic fatty liver disease in South America and Hispanic people, 228
Helma Pinchemel Cotrim and Carla Daltro

21 Alcohol in non-alcoholic fatty liver disease: an oxymoron or a new standard of care?, 234
Achuthan Sourianarayanane, Srinivasan Dasarathy, and Arthur J. McCullough

22 Dietary factors in the pathogenesis and care of patients with fatty liver disease, 248
Giulio Marchesini, Rebecca Marzocchi, Anna S. Sasdelli, Cristiana Andruccioli, and Silvia Di Domizio

23 Metabolic factors and steatosis in patients with hepatitis B and C, 260
Francesco Negro

24 Drug therapy for NASH: insulin-sensitizing agents (metformin and thiazolidinediones), 271
Mohammad S. Siddiqui and Arun J. Sanyal

25 Hepatoprotectants against fatty liver disease: antioxidants, ursodeoxycholic acid, and herbal medicines, 284
Anne Catherine Bürgi and Jean-François Dufour

26 Lipid modifiers and NASH: statins, ezetimibe, fibrates, and other agents, 293

Giovanni Musso, Federica Molinaro, Elena Paschetta, Roberto Gambino, and Maurizio Cassader

Index, 308

Color plate section facing p86