Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon-α and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, ). Sicca syndrome prevalence fell insignificantly (12.7% versus 11%). SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients. 1. Introduction Past clinical understanding confined the burden of chronic hepatitis C infection (HCV) to later stages of hepatic impairment. Now it is known that HCV’s extrahepatic manifestations (EHMs) and reduced health-related quality of life (HRQOL) often develop before hepatic impairment [1]. Diagnostically, this understanding helps uncover underlying HCV in people presenting with associated EHMs and vice versa. Prognostically, it is unclear whether EHMs independently lower HRQOL in HCV patients and whether they respond to antiviral therapy with or without a sustained virological response (SVR). Answers to these questions would help to determine whether the burden of EHMs in HCV patients merits additional management approaches beyond antiviral therapy. HRQOL reduction in HCV is multifactorial. Poor baseline HRQOL is partly psychosocial in origin, relating to the stigma of illness, a history of illicit drug use for a large proportion of patients, and high rates of fatigue, anxiety, and depression [2, 3]. Mood-related aspects of HRQOL may even be organically mediated by HCV
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