Ultrasound and quality of life investigations of people with with chronic Hepatitis C undergoing direct acting antiviral treatment

Introduction: Direct acting antiviral (DAA) therapy became widely available in Ireland in 2015 with successful regimens taking as little as 8-12 weeks, thus changing the paradigm for people living with chronic hepatitis C (CHC). CHC patients are at increased risk of developing liver fibrosis and cirrhosis and the complications of advanced liver disease. CHC infection is also associated with decreased physical and mental health. Liver stiffness measurements (LSMs) can be used to measure determine liver health; FibroScan® and acoustic radiation force impulse (ARFI) imaging are two LSM methods that have been found to correlate well with fibrosis/cirrhosis stage. QoL questionnaires assess the impact of a chronic disease on patient health and wellbeing. This thesis aimed to describe the changes in liver stiffness and QoL over a 96-week period in people living with CHC treated with DAA therapy. Methods: The CHC Treatment Radiographic and Clinical Outcomes Cohort: the TRACER Study was a prospective, observational cohort study that investigated longitudinal LSMs and QoL changes associated with treatment of CHC infection with DAA agents. LSMs were acquired using shear wave elastography, performed using Fibroscan® (right lobe of liver only) and ARFI (right and left lobes of liver and spleen) at baseline, 12 weeks post therapy completion (sustained virological response (SVR)), week 48 and week 96 (after starting therapy) visits. QoL data (captured with HQLQv2), participant demographics, clinical measurements and blood samples were captured at all visits (baseline, week 4, end of treatment (EOT), SVR, week 48 and week 96). Physical component summary (PCS) scores and mental component summary (MCS) scores were calculated from raw QoL data and the changes in LSMs and QoL scores over the study period were examined and the factors which influenced the changes in score such as BMI, age and alcohol and drug use were explored. The relationship between FibroScan® and ARFI scores and the influence of different factors on this relationship were also investigated. Results: The study recruited 88 participants, of whom 72(81.8%), 62(70.5%), 58(65.9%), 58(65.9%) and 51(58%) attended visits at week 4, EOT, SVR, week 48 and week 96, respectively. Three quarters were male and almost all (85(97%)) were Caucasian; 80 participants returned to commence DAA therapy. At baseline, over one third and participants had FibroScan® and ARFI scores >14.5kPa (34(38.6%)) and >1.87m/s 32(36.4%), and there was good correlation between FibroScan® and ARFI at the right lobe of liver (Spearman’s coefficient 0.87[CI 0.80-0.91], p<0.001). 59(67%) and 67(76%) participants recorded a FibroScan® and/or ARFI score at SVR visit or later and the median change in score for these participants was -2.9kPa (p<0.001) and -0.36m/s (p<0.001) over the study duration. Multivariable analysis found no one particular variable to be associated with changes in FibroScan® or ARFI scores over the study duration. In total, 71(80.7%) participants attended at least one of the SVR/week 48/week 96 visits, and all achieved SVR. At baseline, the cohort recorded low MCS scores, but the overall median PCS and MCS scores rose by 9.8% and 14.4% from baseline to week 96 respectively (p<0.001). Having a history of anxiety/depression or any marker of advanced liver disease was associated with lower MCS scores at baseline but slightly higher increases in MCS scores over study duration. Conclusion: Achieving SVR post DAA therapy was associated with improved LSMs and improved QoL. Future studies should focus on longer term outcomes and implementation of community-based treatment programmes with comprehensive liver health screening to reach as many people living with CHC as possible and improve engagement with health services for these people.