Non-Alcoholic Fatty Liver Disease E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 762

Veröffentlichungsjahr: 2013

Beschreibung

The sharp rise in cases of Non-alcoholic fatty liver disease is fast becoming one of the major concerns for hepatologists worldwide. This comprehensive clinical guide explains how to diagnose NAFLD and manage patients according to the best standards of care. Contributors from the world's leading institutions concentrate on patient care, drawing on their extensive experience.

Leseprobe

Table of Contents

Title page

Copyright page

List of Contributors

CHAPTER 1: What is non-alcoholic fatty liver disease (NAFLD), and why is it important?

What is NAFLD?

What is non-alcoholic?

Steatosis and NASH

Pathological definition of NASH

NASH without inflammation or fat? The special case of cryptogenic cirrhosis

Does NAFLD matter?

Do recent advances allow us to suggest a better name than NAFLD?

What isn’t NAFLD?

A practical (clinical) definition of NAFLD

Need for consensus of definitions

Is NAFLD an epidemic, and how common is NASH?

Risk factors

Presentation, clinical features, and associated disorders

Can we prevent NAFLD?

Reversibility of NASH: perspectives on lifestyle, obesity interventions, and drug therapy

CHAPTER 2: NAFLD in the community

Introduction

Defining NAFLD

Diagnosing NAFLD

Prevalence of NAFLD

Conclusions

CHAPTER 3: Pathology of NAFLD

Introduction

Adult fatty liver disease

Fibrosis patterns

Is NAFLD “identical” to ALD?

NAFLD in children

Evaluation of NAFLD and NASH: staging and grading

Technical liver biopsy considerations

CHAPTER 4: The natural history of NAFLD

Introduction

Long-term prognosis of patients with the whole spectrum of NAFLD

Long-term prognosis of patients with simple steatosis or non-alcoholic steatohepatitis (NASH)

Long-term prognosis of patients with NAFLD with advanced fibrosis and cirrhosis

Fibrosis progression in patients with NAFLD

Conclusions and future directions

CHAPTER 5: Emerging concepts on the pathogenesis of non-alcoholic steatohepatitis (NASH)

Introduction

Part 1: The fatty liver and the metabolic context of obesity

Part 2: Evolution from steatosis to NASH: what do we know about pathogenic determinants?

Concluding comments and agenda for future research

CHAPTER 6: Diabetes and NAFLD: why is the connection important?

Introduction

Fatty liver is a major determinant of insulin resistance and the metabolic syndrome

NAFLD and risk of developing type 2 diabetes

NAFLD, diabetes severity, and microvascular chronic complications

Liver-related morbidity and mortality in type 2 diabetes

Diabetes and hepatocellular carcinoma

Implications for treatment

Conclusion and future perspectives

CHAPTER 7: NAFLD and cardiovascular risk factors: implications for vascular disease

Introduction

NAFLD and CVD risk factors

NAFLD and increased prevalence of CVD

NAFLD and increased incidence of CVD

NAFLD and CVD: causal effect or epiphenomenon?

Conclusions

CHAPTER 8: A primary care perspective of fatty liver: diagnosis, management, prescribing, and when to refer

Introduction: fatty liver and the metabolic syndrome

Diagnosis

Evaluation

When to refer

Management

Conclusions

CHAPTER 9: Imaging of NAFLD

Introduction

Imaging evaluation of hepatic steatosis

Imaging evaluation of fibrosis and cirrhosis

Imaging evaluation of non-alcoholic steatohepatitis

Conclusion

CHAPTER 10: Non-invasive methods to determine the severity of NAFLD and NASH

Introduction

Liver biopsy

Non-invasive assessment of hepatic steatosis

Non-invasive assessment of NASH

Non-invasive assessment of fibrosis

The future

CHAPTER 11: Fatigue, quality of life, and psychosocial issues for people with NAFLD

Functional ability in NAFLD

Symptoms in NAFLD

Fatigue in NAFLD

Excessive daytime sleepiness

Autonomic nervous system dysfunction

Depression in patients with NAFLD

Engagement in physical activity

Management of symptoms experienced by patients with NAFLD

CHAPTER 12: Physical activity and cardiovascular fitness in patients with NAFLD: clinical importance and therapeutic implications

Overview of physical activity, exercise, physical fitness, and energy expenditure

Importance of physical activity for health – being sedentary and/or inactive

Measuring physical activity and assessing physical fitness

Potential metabolic and other benefits of exercise in NAFLD

Physical activity and fitness in NAFLD

Intervention studies in NAFLD

Conclusion

CHAPTER 13: NAFLD, obesity, and bariatric surgery

Severe obesity and bariatric surgery

Non-alcoholic fatty liver disease (NAFLD) and bariatric surgery

Closing comments

CHAPTER 14: Genetic predisposition to NAFLD and NASH: implications for pathogenesis, diagnosis, prevention, and management

Introduction

Genome-wide association studies in NAFLD and NASH research

Genetic modifiers of NAFLD pathogenesis and progression

Conclusions

CHAPTER 15: NAFLD in children

Epidemiology

Natural history

Signs and symptoms

Diagnosis

Liver biopsy

Blood biomarkers

Imaging techniques

Treatment

Nonpharmacological interventions

Medications

Conclusions

CHAPTER 16: The pointy end of the NAFLD iceberg: cirrhosis, portal hypertension, and liver failure

Disclaimer

Introduction

Epidemiology

Progression of NASH to cirrhosis

Cryptogenic cirrhosis

Histopathology of late NAFLD and cirrhosis

Clinical outcomes of advanced NAFLD and cirrhosis

Diagnosis and presentation

Treatment of NAFLD cirrhosis and complications

Transplant considerations

Conclusions and future directions

CHAPTER 17: Non-alcoholic fatty liver disease, hepatocellular cancer, and other cancers

Incidence and epidemiology of HCC

Risk factors for HCC

NAFLD, metabolic syndrome, and HCC

HCC can develop in noncirrhotic NAFLD

NAFLD, the metabolic syndrome, and other cancers

Obesity and cancer

Diabetes and cancer

The pathogenesis of HCC in NAFLD

The management of HCC arising in patients with the metabolic syndrome

Surveillance

The diagnosis of HCC

Staging of HCC

Treatment options for HCC

Medical management of HCC

A modified BCLC algorithm for patients with NAFLD and the metabolic syndrome

Future directions

CHAPTER 18: NAFLD in Chinese and South Asian people

Introduction

Taiwan

India

China

Perspectives

CHAPTER 19: Non-alcoholic fatty liver disease in Japan

Introduction

Epidemiology

Risk factors

Prognosis of NASH cirrhosis and characteristics of NASH-related HCC

Pathophysiology and genetic background

Prevention and management

Conclusion

Acknowledgments

CHAPTER 20: Non-alcoholic fatty liver disease in South America and Hispanic people

NAFLD in South America

Non-alcoholic fatty liver disease in Hispanic people

CHAPTER 21: Alcohol in non-alcoholic fatty liver disease: an oxymoron or a new standard of care?

Introduction

“Non-alcoholic” in non-alcoholic fatty liver disease

Benefits of alcohol

Adverse effects of alcohol in NAFLD

Summary and conclusion

CHAPTER 22: Dietary factors in the pathogenesis and care of patients with fatty liver disease

Introduction

The habitual diet of patients with fatty liver disease

Takeaway and fast- and junk-food consumption

Role of dietary carbohydrates – fructose

Role of dietary fat

Alcohol and wine intake and resveratrol

Micronutrients

Coffee consumption

Dietary-induced and cognitive-behavioral treatment to induce weight loss

Conclusions

CHAPTER 23: Metabolic factors and steatosis in patients with hepatitis B and C

Steatosis, diabetes, and hepatitis B

General considerations on the metabolic interactions in hepatitis C

Hepatitis C and glucose metabolism alterations

Hepatitis C and alterations of lipid metabolism

Glucose and lipid metabolic alterations and hepatitis C: does it matter?

Conclusions and implications for management

CHAPTER 24: Drug therapy for NASH: insulin-sensitizing agents (metformin and thiazolidinediones)

Non-alcoholic steatohepatitis (NASH) and insulin resistance

Insulin signaling

Mechanism(s) of insulin resistance

Mechanism of action of thiazolidinedione

Drug trials

Conclusion

CHAPTER 25: Hepatoprotectants against fatty liver disease: antioxidants, ursodeoxycholic acid, and herbal medicines

Introduction

Vitamin E

Betaine

Pentoxifylline

Ursodeoxycholic acid (UDCA)

Iron depletion

Silybin

Berberine

Perspectives for the future

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

Introduction

Cholesterol-lowering drugs

Statins

Combination therapy with statins

Ezetimibe

N-3 polyunsaturated fatty acids (PUFAs)

Probucol

Fibrates

Conclusions

Acknowledgments

Supplemental Images

Index

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Library of Congress Cataloging-in-Publication Data

Non-alcoholic fatty liver disease : a practical guide / edited by Geoffrey C. Farrell, Arthur J. McCullough, Christopher P. Day.

p. ; cm.

 Includes bibliographical references and index.

 ISBN 978-0-470-67317-1 (hardback : alk. paper)

 I. Farrell, Geoffrey C. II. McCullough, Arthur J. III. Day, Christopher Paul.

 [DNLM: 1. Fatty Liver. WI 700]

 616.3'62–dc23

2012044846

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.

Cover image: First image iStock File #4923036 (brakenj), third image iStock File #14083300 (KT TSUJI) and fourth image iStock File #14271207 (IngramPublishing). Second panel image reproduced with permission of Takeshi Yokoo, An Tang and Claude Sirlin. Fifth panel image and background image reproduced with permission of Elizabeth M. Brunt and David E. Kleiner.

Cover design by Grounded Design

List of Contributors

Leon A. Adams MBBS FRACP PhD

Associate Professor

School of Medicine and Pharmacology

University of Western Australia

Sir Charles Gairdner Hospital

Nedlands, WA, Australia

Deepak Amarapurkar MD

Senior Consultant

Department of Gastroenterology

Bombay Hospital & Medical Research Centre

Jagjivanram Hospital

Mumbai, India

Cristiana Andruccioli MD

Resident

Unit of Metabolic Diseases and Clinical Dietetics

University of Bologna

Bologna, Italy

Paul Angulo MD FACG AGAF

Professor of Medicine and Section Chief of Hepatology

Division of Digestive Diseases and Nutrition

University of Kentucky Medical Center

Lexington, KY, USA

Quentin M. Anstee BSc MB BS PhD MRCP(UK)

Senior Lecturer & Honorary Consultant Hepatologist

Institute of Cellular Medicine

Newcastle University;

Freeman Hospital Liver Unit

Newcastle upon Tyne, UK

Elizabeth M. Brunt MD

Professor of Pathology and Immunology

Department of Pathology and Immunology

Washington University School of Medicine

St. Louis, MO, USA

Elisabetta Bugianesi MD PhD

Associate Professor of Gastroenterology

Department of Medical Sciences

Division of Gastro-Hepatology

San Giovanni Battista Hospital

University of Turin

Turin, Italy

Anne Catherine Bürgi MD

Professor

Department of Visceral Surgery and Medicine

Inselspital;

Hepatology, Department of Clinical Research

University of Bern

Bern, Switzerland

Nuala M. Byrne BHMS MAppSc PhD

Professor of Exercise Physiology and Energy Metabolism

School of Exercise and Nutrition Sciences, and

Institute of Health and Biomedical Innovation

Queensland University of Technology

Brisbane, QLD, Australia

Maurizio Cassader PhD

Professor

Department of Medical Sciences

University of Turin

Turin, Italy

Henry Lik-Yuen Chan MD FRCP

Professor

Department of Medicine and Therapeutics

The Chinese University of Hong Kong

Hong Kong, China

Shivakumar Chitturi MD MRCP(UK) FRACP

Senior Lecturer

Gastroenterology and Hepatology Unit

The Canberra Hospital;

Australian National University Medical School

Canberra, ACT, Australia

Helma Pinchemel Cotrim MD PhD

Associate Professor of Medicine

Gastro-Hepatology Unit

Universidade Federal da Bahia

Salvador, Bahia, Brazil

Carla Daltro MD PhD

Professor of Scientific Methodology

PPgMS – Universidade Federal da Bahia

Salvador, Bahia, Brazil

Ann K. Daly BA PhD

Professor of Pharmacogenetics

Institute of Cellular Medicine

Newcastle University

Newcastle upon Tyne, UK

Srinivasan Dasarathy MD

Staff Physician

Department of Gastroenterology and Hepatology

Digestive Disease Institute;

Department of Pathobiology

Cleveland Clinic Lerner Research Institute;

Cleveland Clinic Lerner College of Medicine at Case Western University

Cleveland, OH, USA

Christopher P. Day MA (Cantab) PhD MD FRCP FMedSci

Pro-Vice Chancellor and Provost of Medical Sciences

Faculty of Medical Sciences

Newcastle University

Newcastle upon Tyne, UK

Silvia Di Domizio R. Diet.

Registered Dietitian

Unit of Metabolic Diseases and Clinical Dietetics

University of Bologna

Bologna, Italy

Jean-François Dufour MD

Professor

Department of Visceral Surgery and Medicine

Inselspital;

Hepatology, Department of Clinical Research

University of Bern

Bern, Switzerland

Jian-Gao Fan MD

Professor

Department of Gastroenterology

Xinhua Hospital

Shanghai Jiao-Tong University School of Medicine

Shanghai, China

Geoffrey C. Farrell MD FRACP

Professor of Hepatic Medicine

Australian National University Medical School;

Senior Staff Hepatologist

The Canberra Hospital

Canberra, ACT, Australia

Ariel E. Feldstein MD

Professor of Pediatrics

Chief, Division of Pediatric Gastroenterology

Hepatology and Nutrition

University of California, San Diego

San Diego, CA, USA

James Frith MB ChB MRCP PhD

Academic Clinical Lecturer

UK NIHR Biomedical Research Centre in Ageing – Liver Theme & Institute for Ageing and Health

Newcastle University

Newcastle upon Tyne, UK

Roberto Gambino PhD

Professor

Department of Medical Sciences

University of Turin

Turin, Italy

Janine Graham BSc(Hons) MB CHb

Physician

Northern Centre for Cancer Care

Freeman Hospital

Newcastle upon Tyne, UK

Stephen A. Harrison MD FACP

Professor of Medicine

Uniformed Services University for the Health Sciences;

Division of Gastroenterology

Department of Medicine

Brooke Army Medical Center

San Antonio Military Medical Center

Fort Sam Houston

San Antonio, TX, USA

Ingrid J. Hickman BHSci(Nut & Diet) AdvAPD PhD

Principal Research Fellow

Departments of Nutrition and Dietetics

Princess Alexandra Hospital;

The Mater Medical Research Institute

Mater Mother’s Hospital

Brisbane, QLD, Australia

Yoshito Itoh MD PhD

Associate Professor of Internal Medicine

Department of Gastroenterology

Faculty of Medicine

Kyoto Prefectural University of Medicine

Kyoto, Japan

Jia-Horng Kao MD PhD

Director and Distinguished Professor

Graduate Institute of Clinical Medicine;

Hepatitis Research Center

National Taiwan University College of Medicine and

National Taiwan University Hospital

Taipei, Taiwan

David E. Kleiner MD PhD

Director, Clinical Operations

Chief, Post-Mortem Section

Laboratory of Pathology

National Cancer Institute

National Institutes of Health

Bethesda, MD, USA

Isabelle A. Leclercq MD PhD

Professor

Laboratory of Hepato-gastroenterology

Institut de Recherche Expérimentale et Clinique

Université catholique de Louvain

Brussels, Belgium

Graeme A. Macdonald MBBS PhD FRACP

Senior Staff Specialist

Department of Gastroenterology and Hepatology

Princess Alexandra Hospital;

Associate Professor of Medicine

The University of Queensland

Brisbane, QLD, Australia

Giulio Marchesini MD

Professor of Medicine

Unit of Metabolic Diseases and Clinical Dietetics

University of Bologna

Bologna, Italy

Rebecca Marzocchi MD

Physician

Unit of Metabolic Diseases and Clinical Dietetics

University of Bologna

Bologna, Italy

Philippe Mathurin MD PhD

Professor of Medicine and Section Chief of Hepatology

Service Maladie de l’appareil Digestif

Université Lille

Hôpital Claude Huriez

Lille, France

Arthur J. McCullough MD

Pier C. and Renee A. Borra Family Endowed Chair

Professor of Medicine

Cleveland Clinic Lerner College of Medicine at Case Western Reserve University;

Consultant, Department of Gastroenterology and Hepatology

Digestive Disease Institute;

Staff, Department of Pathobiology

Cleveland Clinic Lerner Research Institute

Cleveland, OH, USA

Federica Molinaro MD

Professor

Department of Medical Sciences

University of Turin

Turin, Italy

Giovanni Musso MD

Professor

Gradenigo Hospital

Turin, Italy

Francesco Negro MD

Adjunct Professor

Divisions of Gastroenterology, Hepatology and Clinical Pathology

University Hospital

Geneva, Switzerland

Julia L. Newton MBBS FRCP PhD

Professor of Ageing and Medicine

UK NIHR Biomedical Research Centre in Ageing – Liver Theme & Institute for Ageing and Health

Newcastle University

Newcastle upon Tyne, UK

Takeshi Okanoue MD PhD

Professor of Internal Medicine and Director

Center of Gastroenterology and Hepatology

Saiseikai Suita Hospital

Osaka;

Department of Gastroenterology

Faculty of Medicine

Kyoto Prefectural University of Medicine

Kyoto, Japan

Elena Paschetta MD

Professor

Department of Medical Sciences

University of Turin

Turin, Italy

Helen L. Reeves BM BS BMedSci PhD

Senior Lecturer and Honorary Consultant Gastroenterologist

Northern Institute for Cancer Research;

Hepatopancreatobiliary Team

The Freeman Hospital

Newcastle upon Tyne, UK

Arun J. Sanyal MBBS MD FACP

Charles Caravati Professor of Medicine

Chairman, Division of Gastroenterology, Hepatology and Nutrition

Virginia Commonwealth University

Richmond, VA, USA

Anna S. Sasdelli MD

Fellow, School of Nutritional Sciences

Unit of Metabolic Diseases and Clinical Dietetics

University of Bologna

Bologna, Italy

Jonathon W. Schwake MD

Gastroenterology Fellow

Division of Gastroenterology

Department of Medicine

Brooke Army Medical Center

San Antonio Military Medical Center

Fort Sam Houston

San Antonio, TX, USA

Mohammad S. Siddiqui MD

Assistant Professor of Medicine

Division of Gastroenterology, Hepatology and Nutrition

Virginia Commonwealth University

Richmond, VA, USA

Claude B. Sirlin MD

Associate Professor of Radiology

Chief, Body Imaging

Chief, Abdominal MRI

Director, Liver Imaging Research Group

University of California, San Diego

San Diego, CA, USA

Achuthan Sourianarayanane MD MRCP

Assistant Professor of Medicine

Center for Liver Diseases

Division of Gastroenterology, Hepatology and Nutrition

University of Pittsburgh

Pittsburgh, PA, USA

An Tang MD

Assistant Professor

Department of Radiology

University of Montreal

Montreal, QC, Canada

Giovanni Targher MD

Assistant Professor

Department of Medicine

Section of Endocrinology and Metabolism

University of Verona

Verona, Italy

Dawn M. Torres MD

Division of Gastroenterology

Department of Medicine

Walter Reed National Military Medical Center

Bethesda, MD, USA

Vincent Wai-Sun Wong MD FRCP

Professor

Department of Medicine and Therapeutics

The Chinese University of Hong Kong

Hong Kong, China

Kohichiroh Yasui MD PhD

Associate Professor of Internal Medicine

Department of Gastroenterology, Faculty of Medicine

Kyoto Prefectural University of Medicine

Kyoto, Japan

Takeshi Yokoo MD PhD

Assistant Professor

Department of Radiology

University of Texas Southwestern Medical Center

Dallas, TX, USA

CHAPTER 1

What is non-alcoholic fatty liver disease (NAFLD), and why is it important?

Geoffrey C. Farrell1, Arthur J. McCullough2 and Christopher P. Day3

1The Canberra Hospital, Canberra, ACT, Australia

2Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, UK

3Newcastle University & Freeman Hospital Liver Unit, Newcastle upon Tyne, UK

Key Points

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of fatty liver disease caused by over-nutrition; most patients show central obesity.NAFLD should be suspected in any overweight person with ultrasound evidence of fatty liver, particularly if metabolic complications such as fasting hyperglycemia, raised serum lipids, and high blood pressure are present.Diagnosis of NAFLD requires exclusion of alcoholic liver disease by a lifetime, quantitative history of alcohol intake: the limits of alcohol intake allowable for a diagnosis of NAFLD are 70 g/week (or one standard drink/day) in women and 140 g/week (two standard drinks/day) in men. Lower levels of alcohol intake may actually protect against liver complications of NAFLD.NAFLD comprises a pathological spectrum from simple steatosis, which rarely leads to liver fibrosis, through steatohepatitis (or NASH), which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC).NAFLD is associated with a 1.7-fold increase in standardized mortality. Premature deaths are from common cancers and cardiovascular disease, with liver complications being third most common.While only liver biopsy reliably indicates NASH versus “not NASH” pathology in NAFLD, there have been recent advances in non-invasive approaches (clinicopathological scores, biomarkers, and transient elastography) to both disease activity and fibrotic severity.Lifestyle measures are the first approach to management of patients with NAFLD; weight loss of >7% appears to improve histology but is achieved in less than 50% of patients.Tight control of serum lipid abnormalities is vital for reducing cardiovascular risk in patients with NAFLD.

What is NAFLD?

Fatty liver is stainable fat in hepatocytes (steatosis). Among many causes, obesity and type 2 diabetes (T2D) have never been controversial. Despite this, there is no mention of non-alcoholic fatty liver disease (NAFLD) in the current iteration of the International Classification of Disease (ICD-10), developed in 1990. After early Japanese reports [1–3], American authors raised the possibility that obesity and T2D could also be associated with fatty liver disease complicated by liver cell injury and inflammation (“steatohepatitis”), as well as fibrosis or cirrhosis [4–6]. The pathological findings included Mallory hyaline (also termed Mallory–Denk bodies) [5–8], which until the mid-1970s had been regarded as a hallmark of alcoholic hepatitis. In light of this older concept, and to combat the skeptical view that these were likely instances of alcoholic liver disease in persons who had failed to disclose their alcohol dependence, Ludwig in 1980 coined the term “non-alcoholic steatohepatitis (NASH)” [5].

What is non-alcoholic?

While useful in its time, the term NASH has several disadvantages. First, it starts with a negative: “not alcohol.” This immediately raises the issue about what level of alcohol intake allows one to conceptualize liver disease as alcohol related or not, as discussed elsewhere [9]. A pragmatic definition of NAFLD stipulating no more than one standard drink per day (i.e. 70 g ethanol/week) for women and no more than two standard drinks per day (140 g ethanol/week) for men was proposed in the first edition of this book [10] and has been used by the National Institutes of Health (NIH) NASH clinical research network (CRN) [11]; this definition has been widely adopted for clinical studies, except in France where a slightly more liberal cut-off is favored [12, 13].