Clinical Dilemmas in Non‐Alcoholic Fatty Liver Disease Clinical Dilemmas in Non‐Alcoholic Fatty Liver Disease EDitED by Roger Williams, CBE the institute of Hepatology Foundation for Liver Research London, UK Simon D. Taylor‐Robinson Digestive Diseases Division imperial College London London, UK this edition first published 2016 © 2016 by John Wiley & Sons, Ltd Registered Office John Wiley & Sons, Ltd, the Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial Offices 9600 Garsington Road, Oxford, OX4 2DQ, UK the Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030‐5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley‐blackwell the right of the author to be identified as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988. All rights reserved. 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Description: Chichester, West Sussex ; Hoboken, NJ : John Wiley & Sons inc., 2016. | includes bibliographical references and index. identifiers: LCCN 2015040510 | iSbN 9781118912034 (pbk.) Subjects: | MESH: Non-alcoholic Fatty Liver Disease. Classification: LCC RC848.F3 | NLM Wi 700 | DDC 616.3/62–dc23 LC record available at http://lccn.loc.gov/2015040510 A catalogue record for this book is available from the british Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Set in 8.75/12pt Minion by SPi Global, Pondicherry, india 1 2016 Contents List of contributors, vii 10 Of men and microbes: Role of the intestinal microbiome in non-alcoholic fatty liver disease, 82 Preface, ix Muhammad Bilal Siddiqui, Mohammed Shadab Siddiqui, and Arun J. Sanyal Part I: Nature of the condition 11 Can genetic influence in non‐alcoholic fatty liver disease be ignored?, 91 1 Non-alcoholic fatty liver disease: Hype or harm?, 3 Yang‐Lin Liu, Christopher P. Day, and Stephen H. Caldwell and Curtis K. Argo Quentin M. Anstee 2 NAFLD: A worldwide problem, 8 12 Is there a mechanistic link between hepatic Joanna K. Dowman, Geoffrey C. Farrell, and steatosis and cardiac rather than liver events?, 103 Philip Newsome Soo Lim 3 Is insulin resistance the principal cause of NAFLD?, 15 Ian F. Godsland, Sanjeev Mehta, Shareen Forbes, Fabian Part III: Diagnosis and Scoring Meienberg, Michael Yee, Simon D. Taylor‐Robinson, and Desmond G. Johnston 13 How to best diagnose NAFLD/NASH?, 113 Vlad Ratziu 4 Paediatric NAFLD: A distinct disease with the propensity for progressive fibrosis, 29 14 The clinical utility of noninvasive blood tests and Emer Fitzpatrick and Anil Dhawan elastography, 124 Emmanuel A. Tsochatzis and Massimo Pinzani 5 Non‐alcoholic fatty liver disease (NAFLD) as cause of cryptogenic cirrhosis, 36 15 Are the guidelines—AASLD, IASL, EASL, and Jay H. Lefkowitch BSG—of help in the management of patients with NAFLD?, 131 6 Is NAFLD different in absence of metabolic syndrome?, 44 Cristina Margini and Jean‐François Dufour Yusuf Yilmaz 16 Imaging methods for screening of hepatic steatosis, 138 7 Occurrence of noncirrhotic HCC in NAFLD, 50 Hero K. Hussain Dawn M. Torres and Stephen A. Harrison 17 Are the advantages of obtaining a liver biopsy outweighed by the disadvantages?, 152 Part II: Factors in Disease Progression Jeremy F. L. Cobbold and Simon D. Taylor‐Robinson 8 Fibrosis progression: Putative mechanisms and molecular 18 Screening for NAFLD in high‐risk populations, 161 pathways, 61 Nader Lessan Wing‐Kin Syn and Anna Mae Diehl 9 When is it NAFLD and when is it ALD?: Part IV: Value of treatment measures Can the histologic evaluation of a liver biopsy guide the clinical evaluation?, 72 19 Defining the role of metabolic physician, 173 Elizabeth M. Brunt and David E. Kleiner Nicholas Finer v vi Contents 20 Should physicians be prescribing or patients Part V: What Does the Future hold? self‐medicating with orlistat, vitamin E, vitamin D, insulin sensitizers, pentoxifylline, or coffee?, 182 24 Molecular antagonists, leptin or other hormones Haripriya Maddur and Brent A. Neuschwander‐Tetri in supplementing environmental factors?, 211 Jonathan M. Hazlehurst and Jeremy W. Tomlinson 21 Effects of treatment of NAFLD on the metabolic syndrome, 189 25 What is the role of antifibrotic therapies Hannele Yki‐Järvinen in the current and future management of NAFLD?, 218 22 What are the dangers as well as the true Natasha McDonald and Jonathan Fallowfield benefits of bariatric surgery?, 196 Andrew Jenkinson 26 Developmental programming of non‐alcoholic fatty liver disease, 226 23 Liver transplantation: What can it offer?, 203 Jiawei Li, Paul Cordero, and Jude A. Oben Roger Williams Index, 232 List of contributors Dr Quentin M. Anstee Professor Anil Dhawan National Centre for Cardiovascular Institute of Cellular Medicine Paediatric Liver Centre, King’s College Prevention and Outcomes Newcastle University London School of Medicine UCL Institute of Cardiovascular Science Newcastle upon Tyne, UK; King’s College Hospital London, UK Liver Unit, Freeman Hospital London, UK Newcastle upon Tyne, UK Dr Emer Fitzpatrick Professor Anna Mae Diehl Paediatric Liver Centre, King’s College Professor Curtis K. Argo Division of Gastroenterology L ondon School of Medicine Division of Gastroenterology and Hepatology Department of Medicine King’s College Hospital University of Virginia Duke University, Durham, NC, USA London, UK Charlottesville, VA, USA Dr Joanna K. Dowman Dr Shareen Forbes Professor Elizabeth Department of Gastroenterology and Endocrinology Unit, University/BHF Hepatology M. Brunt C entre for Cardiovascular Science Queen Alexandra Hospital, Portsmouth, UK Department of Pathology and Immunology Queen’s Medical Research Institute Washington University School of Medicine Professor Jean‐François University of Edinburgh St. Louis, MO, USA Edinburgh, UK Dufour University Clinic for Visceral Surgery Professor Stephen and Medicine Dr Ian F. Godsland H. Caldwell Inselspital University of Berne Division of Diabetes Endocrinology Division of Gastroenterology and Bern, Switzerland and Metabolism Hepatology Department of Medicine University of Virginia Dr Jonathan Fallowfield Faculty of Medicine Charlottesville, VA, USA MRC/University of Edinburgh Centre for Imperial College London Inflammation Research London, UK Dr Jeremy F. L. Cobbold Queen’s Medical Research Institute Oxford University Hospitals NHS Trust University of Edinburgh Dr Stephen A. Harrison Oxford, UK Edinburgh, UK Division of Gastroenterology Department of Medicine Professor Geoffrey C. Farrell Dr Paul Cordero San Antonio Military Medical Center The Canberra Hospital Institute for Liver and Digestive Health Fort Sam Houston Australian Capital Territory, Australia; University College London San Antonio, TX, USA Department of Hepatic Medicine London, UK Australian National University Canberra, Australia Dr Jonathan M. Hazlehurst Professor Christopher P. Day Centre for Diabetes, Endocrinology and Institute of Cellular Medicine, Newcastle Professor Nicholas Finer Metabolism University Centre for Weight Loss, Metabolic and School of Clinical and Experimental Newcastle upon Tyne, UK; Endocrine Surgery Medicine Liver Unit, Freeman Hospital University College London Hospitals, University of Birmingham Newcastle upon Tyne, UK London, UK Birmingham, UK vii viii List of contributors Professor Hero K. Hussain Dr Sanjeev Mehta Dr Wing‐Kin Syn Department of Radiology and MRI London North West Healthcare NHS Trust Foundation for Liver Research University of Michigan Health System and Department of Diabetes and Institute of Hepatology Ann Arbor, MI, USA Endocrinology London, UK Imperial College London, Ealing Hospital Mr Andrew Jenkinson London, UK Professor Clinical Lead Department of Metabolic Simon D. Taylor‐Robinson Dr Fabian Meienberg and Bariatric Surgery, University College Digestive Diseases Division Department of Diabetology London Hospital, London, UK Imperial College London Endocrinology and Metabolism London, UK Professor Desmond University Hospital Basel Basel, Switzerland G. Johnston Professor Department of Medicine, Faculty of Medicine Dr Brent Jeremy W. Tomlinson Imperial College London, London, UK A. Neuschwander‐Tetri Oxford Centre for Diabetes, Division of Gastroenterology and Hepatology Endocrinology and Metabolism Dr David E. Kleiner Saint Louis University University of Oxford Laboratory of Pathology St. Louis, MO, USA Churchill Hospital National Cancer Institute Headington, UK National Institutes of Health Professor Philip Newsome Bethesda, MD, USA Institute of Biomedical Research Dr Dawn M. Torres The Medical School Division of Gastroenterology Professor Jay H. Lefkowitch University of Birmingham Department of Medicine Department of Pathology and Cell Biology Birmingham, UK Walter Reed National Military Medical College of Physicians and Surgeons Center Columbia University, New York, NY, USA Dr Jude A. Oben Bethesda, MD, USA Institute for Liver and Digestive Health, Dr Nader Lessan University College London Dr Emmanuel A. Tsochatzis Imperial College London Diabetes Centre London, UK; Abu Dhabi, United Arab Emirates, Department of Gastroenterology and Institute for Liver and Digestive Health Imperial College London, United Kingdom Hepatology, Guy’s and St Thomas’ Hospital University College London Royal Free Hospital NHS Foundation Trust Ms Jiawei Li London, UK London, UK Institute for Liver and Digestive Health University College London, London, UK Professor Massimo Pinzani Professor Institute for Liver and Digestive Health Roger Williams, CBE Dr Soo Lim University College London The Institute of Hepatology Department of Internal Medicine, Royal Free Hospital Foundation for Liver Research Seoul National University College of Medicine London, UK London, UK Seoul National University Bundang Hospital Seoul, Korea Professor Vlad Ratziu Dr Michael Yee Service d’hépatogastroentérologie Metabolic Medicine Unit Dr Yang‐Lin Liu Hôpital Pitié salpêtrière St Mary’s Hospital Institute of Cellular Medicine Institute for Cardiometabolism and Nutrition London, UK Newcastle University Université Pierre et Marie Curie Newcastle upon Tyne, UK Paris, France Professor Yusuf Yilmaz Dr Haripriya Maddur Dr Arun J. Sanyal Department of Gastroenterology Division of Gastroenterology and Hepatology Virginia Commonwealth University School of Medicine, Marmara University Saint Louis University, St. Louis, MO, USA Richmond, VA, USA Istanbul, Turkey Dr Cristina Margini Dr Mohammad Bilal Siddiqui Professor Hepatology, Department of Clinical Research Department of Internal Medicine Hannele Yki‐Järvinen University of Bern, Bern, Switzerland University of Texas Medical School Department of Medicine Houston, Texas, USA University of Helsinki Dr Natasha McDonald Helsinki, Finland Mohammad Shadab MRC/University of Edinburgh Centre for Inflammation Research Siddiqui Queen’s Medical Research Institute Virginia Commonwealth University University of Edinburgh, Edinburgh, UK Richmond, VA, USA