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Nutritional Status and Body Composition in Patients with Chronic 2807710353 Nutritional Status and Body Composition in Patients with Chronic Liver Disease Angela Maiy Madden Royal Free Hospital i' i i r Submitted for the degree of Doctor of Philosophy Royal Free Hospital School of Medicine University of London March 1998 ProQuest Number: 10015918 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10015918 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 i6 i S iK-i k r V y= ^ à fL^fi^.* i LW wB i iJ ti— ^ '. • ; - -/ 1 i ^ **» ABSTRACT Patients with chronic liver disease are often malnourished. Clinical assessment of nutritional status is difficult in this patient population because of the confounding effects of abnormalities of hydration status and protein metabolism. To overcome these difficulties, a global method of assessment incorporating objective and subjective data was developed. Its reproducibility and internal validity were confirmed and it was used to assess the prevalence of malnutrition in 215 patients with cirrhosis. The relationship between global nutritional status and outcome was examined in 271 liver transplant candidates. Pre-transplant malnutrition was significantly associated with a reduced survival 90 days after surgery. Many factors contribute to impaired nutritional status in patients with cirrhosis. The potential effects of hypermetabolism were examined by measuring resting energy expenditure in 1 0 0 patients with cirrhosis and a group of comparable healthy volunteers. Resting energy expenditure was significantly higher in the patients when adjusted for fluid retention and fat-free mass, determined using anthropometry. Further nutrition research in patients with chronic liver disease is hampered by an absence of validated methods of accurately assessing body composition. Such data are required, not only to fully validate clinical assessment techniques, but also to quantify metabolically active tissue and fat compartments which are essential prerequisites in energy expenditure, protein turnover and nutrition intervention studies. The difficulties of assessing body composition in chronic liver disease may be overcome by using a four-compartment model in which total body water, mineral, fat and protein are assessed. This model was applied to 20 patients with cirrhosis who underwent underwater weighing, deuterium dilution and dual-energy X-ray absorptiometry studies. The results were compared with bedside methods of assessments and significant differences found. The hydration fraction of fat-free mass varied between 71.7-83.0%. Although this model of body composition assessment is a research tool, it has shown the limitations of other techniques and provided data upon which further studies can be based. I i :) i fhU CONTENTS Abstract 2 List of tables 7 List of figures 10 Abbreviations 11 Acknowledgements 13 Introduction 16 Chapter 1 The assessment of nutritional status in patients with chronic liver disease 1.1 Outline 23 1.2 Introduction 24 1.3 Nutrient intake 25 1.4 Anthropometry 26 1.5 Biochemical variables 29 1.6 Immune function 30 1.7 Muscle function 31 1.8 Clinical nutritional status 32 1.9 Other assessment methods 33 1.10 Summary 34 1.11 Study 1; A new global assessment method for evaluating nutritional status in patients with cirrhosis 1.11.1 Aims 35 1.11.2 Patients, methods and results 35 1.11.3 Discussion 42 Chapter 2 The prevalence of malnutrition in patients with chronic liver disease 2.1 Outline 53 2.2 Introduction 53 2.3 Nutrient intake 54 2.4 Anthropometry 54 4 2.5 Muscle function ; . - . , 5 5 2.6 Clinical nutritional status 55 2.7 Prevalence of malnutrition and severity of liver disease 55 2.8 Prevalence of malnutrition and aetiology of liver disease 55 2.9 Summary 56 2.10 Study 2: A survey of the prevalence of malnutrition in patients with cirrhosis 2 .1 0 . 1 Aim 56 2 .1 0 . 2 Patients 57 2.10.3 Assessment of nutritional status 57 2.10.4 Statistical analysis 59 2.10.5 Results 59 2 .1 0 . 6 Discussion 64 Chapter 3 The relationship between malnutrition and adverse clinical outcome in patients with chronic liver disease 3.1 Outline 85 3.2 Introduction 85 3.3 Nutritional status and outcome in liver disease 8 6 3.4 Nutritional status and prognostic indices for use in patients with cirrhosis 8 8 3.5 Nutritional status and outcome in patients with liver disease undergoing abdominal surgery 89 3.6 Nutritional status and clinical outcome in patients undergoing liver transplantation 90 3.7 Summary 93 3.8 Defining clinical outcome 94 3.9 Study 3: An investigation into the association between pre-operative nutritional status and liver transplant survival 3.9.1 Aim 95 3.9.2 Patients 95 3.9.3 Nutritional assessment 96 3.9.4 Transplant outcome 98 5 3.9.5 Statistical analysis 98 3.9.6 Results 99 3.9.7 Discussion 100 Chapter 4 Factors contributing to malnutrition in cirrhosis: The role of hypermetabolism 4.1 Outline 117 4.2 Introduction 117 4.3 Nutrient intake 118 4.4 Nutrient loss 125 4.5 Nutrient utilization 128 4.6 Summary 133 4.7 Resting energy expenditure in cirrhosis 134 4.8 Study 4: Assessment of resting energy expenditure in an unselected group of patients with cirrhosis 4.8.1 Aim 140 4.8.2 Patients and volunteers 140 4.8.3 Assessment of nutritional status 141 4.8.4 Preparation for REE measurement 142 4.8.5 Indirect calorimetry 143 4.8.6 Predicted resting energy expenditure 145 4.8.7 Statistical analysis 146 4.8.8 Results 146 4.8.9 Discussion 153 Chapter 5 The assessment of body composition in patients with cirrhosis 5.1 Outline 189 5.2 Introduction 190 5.3 Densitometry 191 5.4 Dilution techniques 193 5.5 Total body potassium 196 5.6 Neutron activation 197 5.7 Dual energy x-ray densitometry 199 6 5.8 Anthropometry 202 5.9 Bioelectrical impedance analysis 207 5.10 Imaging techniques 209 5.11 Near infrared interactance 211 5.12 Urinary metabolite excretion 212 5.13 Single body composition techniques in cirrhosis 214 5.14 Multi-compartment models of body composition assessment 214 5.15 The four-compartment model 216 5.16 Study 5: The measurement of gastrointestinal gas 5.16.1 Aims 218 5.16.2Patients and methods 218 5.16.3 Results 2 2 2 5.16.4 Discussion 223 Study 6 : An evaluation of sampling times for dilution studies in patients with cirrhosis 5.17.1 Aim 227 5.17.2 Patients and methods 227 5.17.3 Statistical analysis 230 5.17.4 Results 231 5.17.5 Discussion 232 5.18 Study 7: Assessment of body composition in patients with cirrhosis using a four-compartment model 5.18.1 Aims 235 5.18.2 Patients and methods 235 5.18.3 Statistical analysis 240 5.18.4 Results 241 5.18.5 Discussion 242 Conclusions 271 Future Work 272 Appendix 275 References 278 LIST OF TABLES 1.1 Subjective Global Assessment data collection sheet 45 1.2 Assessment of nutritional status in chronic liver disease using composite methods 46 1.3 Demographic details of the patients in Study 1 47 1.4 Repeatability coefficients of anthropometric variables 48 1.5 Interobserver agreement and relationship with modified SGA in Study 1 Phase 1 49 1.6 Agreement in nutritional category in Study 1 Phase 2 50 1.7 Inter observer agreement and relationship with RFH GA in Study 1 Phase 3 51 2.1 Body weight in chronic liver disease 67 2.2 Triceps skinfold measurements in chronic liver disease 6 8 2.3 Mid-arm muscle circumference in chronic liver disease 69 2.4 Nutritional status in chronic liver disease using clinical methods 70 2.5 Nutritional status and severity of chronic liver disease 71 2.6 Nutritional status and aetiology of chronic liver disease 72 2.7 Aetiology and severity of liver disease in Study 2 73 2.8 Gastrointestinal symptoms in patients with cirrhosis 74 2.9 Anthropometric measurements in patients with cirrhosis 75 2.10 Global nutritional status and anthropometric variables 76 2.11 Severity of liver disease and nutritional variables 77 2.12 Aetiology of liver disease and nutritional variables 78 2.13 Grip-strength and global nutritional status and severity of liver disease 79 3.1 Nutritional variables and outcome in chronic liver disease 107 3.2 Nutritional variables and outcome in patients with chronic liver disease undergoing surgery 108 3.3 Nutritional variables and outcome in liver transplantation 109 8 3.4 Aetiology of patients in Study 3 110 3.5 Pre-transplant nutritional status 110 3.6 Survival after liver transplantation 1 1 1 3.7 Post-transplant survival: Objective pre-transplant nutritional variables 1 1 2 3.8 Post-transplant survival: Pre-transplant nutrient intake 113 3.9 Post-transplant survival: Pre-transplant weight change 114 4.1 Nutrient intake in patients with chronic liver disease 161 4.2 Demography of patients with cirrhosis in REE studies 163 4.3 Procedural details of REE studies in cirrhosis 165 4.4 REE in patients with cirrhosis and healthy volunteers 168 4.5 Critical evaluation of REE studies in cirrhosis 169 4.6 Aetiology and severity of liver disease in Study 4 170 4.7 Demographic and anthropometric data in cirrhotic patients and healthy volunteers in Study 4 171 4.8 Demographic and anthropometric data in patients with and without
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