Nonalcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a common cause of elevated liver enzymes and chronic liver disease in Western countries. NAFLD is characterized by elevated liver enzymes in the absence of alcohol consumption and secondary causes of liver disease. It is an independent predictor of future risk of cardiovascular diseases, type 2 diabetes and metabolic syndrome (hypertension, abdominal obesity, dyslipidemia, glucose intolerance). This book is a quick reference guide for medical students and professionals about NAFLD. Readers will find a summary of epidemiology, clinical features, diagnosis, imaging techniques, histopathology, and disease management. The book also presents information about NAFLD linked with hepatocellular carcinoma and guidelines for treating NAFLD in pediatric patients. Each chapter presents information in a simple, structured manner making this text an ideal handbook for supplementing hepatology modules in medical curricula. CONTENTS 6 FOREWORD 10 PREFACE 11 List of Contributors 12 Epidemiology of NAFLD 13 Alajos Par* 13 INTRODUCTION 14 PREVALENCE OF NAFLD AND NASH 15 Liver Biopsy and Autopsy Studies 15 Ultrasound (US) 16 Magnetic Resonance Imaging (MRI) 16 Non-invasive Biomarker for Fibrosis: Fibrotest 16 Elevation in Liver Enzymes and Combinations of Clinical Variables 17 RISK FACTORS 17 Age 17 Gender 18 Race, Ethnicity and Gene Variants 18 Metabolic Disorders 19 Polycystic Ovarian Syndrome (PCOS) 19 Hepatitis C Virus (HCV) 20 NATURAL HISTORY 20 BRIEFLY ON NAFLD AND CARDIOVASCULAR DISEASE (CVD) 22 SUMMARY 22 CONFLICT OF INTEREST 23 ACKNOWLEDGEMENTS 23 REFERENCES 23 Clinical Manifestations and Diagnosis of NAFLD 31 István Tornai* 31 INTRODUCTION 32 Extrahepatic Complications of NAFLD 33 Cardiovascular Disorders and NAFLD 33 Chronic Kidney Disease and NAFLD 35 Osteoporosis and NAFLD 35 Endocrinopathies 36 Hypothyroidism 36 Polycystic Ovarian Syndrome 36 Obstructive Sleep Apnea Syndrome 37 Carcinogenesis and NAFLD 37 Colorectal Cancer 37 Progression of Liver Disease in NAFLD 38 Patients with Risk of Progression 38 Cirrhotic NASH 39 Alcohol and NAFLD 39 NASH in Lean Patients 40 Diagnosis of NAFLD 40 CONFLICT OF INTEREST 41 ACKNOWLEDGEMENTS 41 REFERENCES 41 Imaging of NAFLD 46 Zoltán Harmat* and Omar Giyab 46 INTRODUCTION 46 IMAGING MODALITIES 47 Ultrasound 47 Sonoelastography 48 Computed Tomography 49 Magnetic Resonance Imaging 51 Chemical Shift Imaging 52 Fast SE Imaging 53 MR Spectroscopy 53 MR Elastography 53 CONCLUSION 54 CONFLICT OF INTEREST 54 ACKNOWLEDGEMENTS 55 REFERENCES 55 Histopathological Changes of NAFLD 56 Peter Nagy* 56 INTRODUCTION 56 GENERAL HISTOLOGICAL FEATURES OF NAFLD 58 THE ROLE AND VALUE OF LIVER BIOPSY IN THE DIAGNOSIS AND TREATMENT OF NAFLD PATIENTS 60 HISTOLOGICAL CHARACTERISTICS OF NAFLD 62 Steatosis 62 Inflammation 66 Hepatocellular Injury, Ballooning 67 Liver Fibrosis and Ductular Reaction 70 NAFLD-RELATED CIRRHOSIS 73 NAFLD AND HEPATOCELLULAR CARCINOMA 73 PEDIATRIC NAFLD 75 HISTOLOGICAL SCORING OF NAFLD 77 DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS 79 CONFLICT OF INTEREST 80 ACKNOWLEDGEMENTS 80 REFERENCES 81 Pathophysiology of NAFLD 87 Gabriella Par* 87 INTRODUCTION 87 EXTRAHEPATIC AND INTRAHEPATIC MECHANISMS IN NAFLD 89 Extrahepatic Mechanisms 89 Intrahepatic Mechanisms 90 Enzymes 90 Transcription Factors 90 GENETICS AND EPIGENETIC EFFECTS 91 Genetics 91 Epigenetic Effects 92 ADIPOKINES 92 OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS 93 INSULIN RESISTANCE (IR) 94 OBESITY 95 APOPTOSIS 95 HEPATOCYTE SENESCENCE 96 IMMUNE RESPONSE 97 Toll-like Receptors 98 Th17 Response 99 FIBROSIS, HEPATOCYTE BALLOONING, HEDGEHOG PATHWAY AND VITAMIN E IN NASH 99 Hepatocyte Ballooning 100 Hedgehog Pathway 100 Vitamin E 102 SUMMARY 104 CONFLICT OF INTEREST 105 ACKNOWLEDGEMENTS 105 REFERENCES 105 Metabolic Diseases and NAFLD 113 Tatjana Ábela,b,* 113 INTRODUCTION 113 OBESITY 114 TYPE 2 DIABETES 116 LIPID DISORDERS 116 HYPERTENSION 118 METABOLIC SYNDROME 119 CONCLUDING REMARKS 120 CONFLICT OF INTEREST 120 ACKNOWLEDGEMENTS 120 REFERENCES 120 Management of NAFLD 129 Krisztina Hagymási* and Gabriella Lengyel 129 INTRODUCTION 129 Treatment 131 Reduction of Body Weight 131 Diet 132 Physical Activity 133 Pharmacotherapy 133 Improving Insulin Sensitivity 134 Reduction of Lipid Levels 136 Antioxidants 136 Ursodeoxycholic Acid 137 Liver Transplantation 137 CONCLUDING REMARKS 138 CONFLICT OF INTEREST 139 ACKNOWLEDGEMENTS 140 REFERENCES 140 Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma 147 György Baffy* 147 INTRODUCTION 147 RISK FACTORS OF HCC IN NAFLD 148 Obesity and Diabetes 148 NAFLD with Advanced Fibrosis 149 NAFLD without Advanced Fibrosis 149 Concurrent Chronic Liver Disease 150 MOLECULAR MECHANISMS OF HCC DEVELOPMENT IN NAFLD 151 Oncogenic Pathways in Cirrhosis 151 Genetic Variability and Predisposition to NAFLD-HCC 151 Adipose Expansion and Adipokine Imbalance 152 Lipotoxicity 153 Insulin Resistance 154 Altered Gut Microbiota 155 MicroRNAs and Hepatocarcinogenesis 155 DIAGNOSIS OF NAFLD-HCC 156 Clinical Presentation 156 Biomarkers of HCC Development in NAFLD 157 RISK REDUCTION STRATEGIES FOR HCC COMPLICATING NAFLD 157 Screening and Surveillance 157 Lifestyle Measures 158 Insulin-sensitizing Agents 159 Emerging Opportunities for Chemoprevention 159 PERSPECTIVES 160 CONFLICT OF INTEREST 161 ACKNOWLEDGEMENTS 161 REFERENCES 161 Non-Alcoholic Fatty Liver Disease in the Pediatric Population 174 Zsuzsanna Almássy* 174 INTRODUCTION 174 EPIDEMIOLOGY, PATHOGENESIS 175 NAFLD AND CVD IN CHILDREN 178 RISK AND DEVELOPMENT OF NAFLD 179 DEVELOPMENT OF NAFLD 180 DIAGNOSIS AND PROGNOSIS 180 THERAPY AND FOLLOW-UP OF PATIENTS 182 CONCLUSION 183 CONFLICT OF INTEREST 183 ACKNOWLEDGEMENTS 184 REFERENCES 184 SUBJECT INDEX 187