Lifestyle as Therapy for Liver Disease

Abstract

Liver disease is the most rapidly growing chronic disease in the UK. ‘Liver disease’ comprises a vast range of aetiologies. Non-alcoholic fatty liver disease (NAFLD) is an individual aetiology that encompasses a range of disease severities, from simple fatty liver through to advanced fibrosis and cirrhosis of the liver. It is estimated that up to 33% of adults within the Western population have NAFLD, with up to 11% of those developing advanced liver disease. It is predicted that by 2030, NAFLD will be the leading indication for liver transplantation. The aim of this thesis was to assess the potential role of lifestyle intervention as a therapy for advanced liver disease including patients awaiting liver transplantation. NAFLD is strongly associated with excessive caloric consumption, sedentary behaviour, and being overweight/obese. In the absence of approved pharmacological treatments, weight loss through lifestyle modification is the primary recommended therapy. It has been shown that a weight loss of >10% body weight is strongly associated with resolution of fibrosis, however, in practise, only a minority of patients manage to achieve and sustain this magnitude of weight loss. Following a statistical analysis whereby all thirty participants were considered, irrespective of whether they completed the intervention, Chapters 3 and 4 demonstrate that a very low calorie diet (~800kcals/day) is a safe, feasible and acceptable intervention to achieve a >10% weight loss in 34% of patients with advanced NAFLD to nine months. Chapter 5 describes differences in levels of physical activity and inactivity between patients with advanced NAFLD and age- and gender-matched healthy controls, further corroborating the need for targeted physical activity interventions for patients with NAFLD. Specifically, patients with NAFLD spent more time inactive, and less time engaging in physical activity of light, moderate, vigorous and moderate-vigorous intensities than age and gender matched healthy controls. Chapter 6 describes the development of a tailored exercise programme and an embedded retrospective cohort analysis, targeting the fitness of patients on the liver transplantation waiting list, would be acceptable to patients. The retrospective cohort analysis described clinical measures which are obtained as part of the decision making process to determine suitability for receiving a liver transplant. Data obtained from the retrospective cohort analysis demonstrated that poor cardiorespiratory fitness and other “unhealthy” lifestyle behaviours were major determinants of patients not being wait-listed for liver transplant. In conclusion, this thesis suggests that lifestyle interventions could be employed as acceptable and feasible strategies to achieve weight loss and reduce disease progression in patients with advanced NAFLD. Furthermore, this thesis proposes that clear, structured recommendations for lifestyle behaviours be implemented into clinical care pathways for patients with lifestyle related liver disease across the disease spectrum