An Examination of Physical Activity, Cardiorespiratory Fitness and Cardio-metabolic Health through the Modern Hepatitis C Continuum

Abstract

Hepatitis C (HCV) is an established global health issue with an approximated worldwide incidence of 3%. Hepatic features of chronic hepatitis C; such as hepatic fibrosis, steatosis and cirrhosis, and extrahepatic features such as insulin resistance, type 2 diabetes and atherosclerosis can predispose individuals with HCV to an elevated risk of both liver-related and cardiovascular-related morbidity and mortality, in comparison to the general population. Obesity, physical inactivity and poor cardiorespiratory fitness further compounds this risk. The protective effects of regular moderate to vigorous-intensity physical activity and thus adequate cardiorespiratory fitness on all-cause morbidity and mortality are well established in the general population. Additionally, the anti-inflammatory attributes of exercise have the potential to ameliorate both hepatic and extra hepatic features of chronic hepatitis C. Therefore, this thesis aimed to assess physical activity, cardiorespiratory fitness and measures of cardio-metabolic health throughout the modern HCV continuum, with a view to determining the necessity and merit of an aerobic exercise intervention in this cohort. Work for this thesis commenced with a literature review investigating the existing research in the area of aerobic exercise and physical activity in the management of hepatic and extrahepatic features of hepatitis C. Following on from this was Study 1a, a cross sectional examination of habitual physical activity, cardiorespiratory fitness and cardio-metabolic health in 155 individuals living with chronic hepatitis C. Low levels of physical activity and poor cardiorespiratory fitness were a prominent feature in the cohort The results of Study 1a prompted 3 further studies; (i) an investigation of the effects of achieving sustained virological response on habitual physical activity, cardiorespiratory fitness levels and measures of cardio-metabolic health in individuals with hepatitis C (Study 1b) (ii) an examination of perceived barriers and motivators to engaging in physical activity in individuals living with hepatitis C (Study 2), and (iii), an investigation of respiratory function, cardiorespiratory fitness and physical activity in both HCV RNA positive and HCV RNA negative persons who currently engage in polysubstance use (Study 3). Collectively, the results of this thesis indicate poor levels of physical activity, cardiorespiratory fitness and widespread obesity in Irish individuals living with chronic hepatitis C. Furthermore, dyslipidaemia was apparent at SVR24, demonstrating the need for extended monitoring of cardio-metabolic health profile post DAA therapy. Moreover, this indicates a specific and prescriptive aerobic exercise regimen in this cohort warrants investigation, both in treated and untreated individuals with hepatitis C. However, challenges present in terms of study recruitment and attendance. Thus, preliminary strategies aimed at enacting positive health behaviour change and an examination of the feasibility of conducting such lifestyle interventions in this cohort are also advised.