Exercise Therapy as a Treatment for Chronic Liver Disease

Abstract

Hepatitis C (HCV) and Non-Alcoholic Fatty Liver Disease (NAFLD) are among the leading causes of chronic inflammatory liver disease. HCV and NAFLD present with numerous hepatic and extrahepatic features which culminates in an increased cardiometabolic risk and accelerates liver disease progression. The extensive benefits of physical activity (PA) and high cardiorespiratory fitness (CRF) are well recognised in both the general population and in many chronic diseases but the extent of the benefits in HCV and NAFLD populations remains unclear. This thesis aimed to establish the cardiometabolic profile as well as CRF and PA levels in a cohort of individuals with HCV and NAFLD and subsequently determine the effects of an aerobic exercise intervention (EI) for treating the hepatic and extrahepatic features of both HCV and NAFLD.

Study 1 aimed to determine the effects of a 12-week aerobic EI on cognitive and cardiometabolic health in a cohort of individuals with HCV. 75 participants with HCV-related cognitive impairment completed the baseline assessment. Overall, there were low PA levels with only 25% of participants achieving the recommended weekly PA guidelines and 59% of participants had poor CRF. 43% of participants also had evidence of central obesity, 24% had metabolic syndrome, 90% reported moderate/severe fatigue, 78% reported poor sleep quality and 39% reported depression. Following the assessment, 31 participants completed the EI (exercise group n=13, control group n=18) which resulted in significant improvements in measures of cognitive function, CRF and quality of life. When participants were reassessed 12 weeks after the completion of the EI, the benefits were not sustained.

Study 2a aimed to determine the cardiometabolic profile, CRF and PA levels in a cohort of individuals with NAFLD and a total of 87 participants completed the assessment. 20% of the cohort were achieving the PA guidelines, 87% had poor CRF, 100% were overweight or obese, 72% had metabolic syndrome, 92% had central obesity,79% reported moderate/severe fatigue and 64% reported poor sleep quality. Participants with more severe hepatic fibrosis had significantly worse CRF compared to those with minimal/moderate hepatic fibrosis. Following Study 2a, Study 2b aimed to determine the effects of a 12-week aerobic EI on the hepatic and extrahepatic features of NAFLD. A total of 24 participants completed the EI (exercise group n=16, control group n=8). Following the EI, there was a significant regression in histologically measured hepatic fibrosis and hepatocellular ballooning which was paralleled by significant improvements in CRF and anthropometry, but no participants achieved the published benchmark for clinically significant weight loss (7-10%). Upon further analysis, the significantly improved histological endpoints were associated with improvements in CRF. When participants were reassessed after 12 and 52 weeks, the majority of the benefits were not sustained.

Study 3 aimed to determine the perceived barriers and motivators to engaging in PA in a cohort of individuals with NAFLD and a total of 108 participants completed the study. The most frequently cited barrier to engaging in PA was lack of willpower and the most frequently cited motivator to engaging in PA was maintaining one?s health and fitness. Participants were also asked to self-report their PA levels and their knowledge of the weekly PA guidelines and it was found that 41% were sufficiently active and 23% were aware of the weekly PA guidelines.

Taken collectively, the results of this thesis highlight the significantly elevated cardiometabolic risk in both the HCV and NAFLD cohorts investigated which was compounded by low PA levels and poor CRF. There were significant positive benefits of exercise for treating the hepatic and extrahepatic features of HCV and NAFLD as evidenced by the significant improvements in cognitive function and quality of life in Study 1 and histologically measured hepatic fibrosis and hepatocellular ballooning in Study 2b as well as improvements in cardiometabolic health and CRF in both interventional studies. That the benefits of the EI were not sustained longitudinally in both studies indicates the need to determine strategies to transition exercise into the community setting and promote lifelong adherence to the therapy.