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Objective Hepatitis C virus (HCV) causes neuropsychiatric disorders and quality of life impairment, especially in patients with cryoglobulinemic vasculitis (CV). Direct acting antivirals (DAAs) are effective in most extrahepatic HCV diseases, but limited information exists regarding the outcome of psychiatric disorders in patients with and without CV, after therapy. We aimed to evaluate psychiatric outcomes, in HCV-patients with and without CV, before and after successful DAA therapy. Methods We prospectively studied DAA-treated HCV-patients, stratified into presence (CV) or absence of CV (NON-CV). Four psychometric scales were administered to assess depression (HAM-D and MADRS), anxiety (HAM-A), and mania (MRS). Short-Form-36 questionnaires evaluated quality of life. Results Seventy-six patients were recruited, and 47 CV and 29 NON-CV were treated with antivirals. At baseline, depression and anxiety, from mild to severe, were frequently shown, with the most advanced cases in thee CV group; no patients achieved the scores for mania. A significant improvement emerged for all the psychometric scales in the entire population and in the subgroups, after viral eradication even in the short-term outcome. The Short-Form-36 summary components showed benefits. Conclusions After HCV eradication, the depression and anxiety scores significantly improved and severity grade generally lowered. DAA-positive effects on mental disorders should be considered part of the therapy outcome, being beneficial especially in CV patients who usually have worse baseline mental scores.   Key Points • HCV frequently causes psychiatric disorders and an often-invalidating autoimmune/lymphoproliferative disease called cryoglobulinemic vasculitis.• The new direct acting antivirals (DAAs) are very effective and well tolerated by HCV-patients.• This study shows DAA-induced benefits on depression and anxiety in HCV-patients that are especially evident in CV patients who usually have worse baseline mental scores.• DAA-induced benefits are observed in the short-term post-therapy follow-up, in contrast with data previously obtained in HCV patients treated with IFN-based anti-HCV therapy.

Rapid improvement of psychiatric stigmata after IFN-free treatment in HCV patients with and without cryoglobulinemic vasculitis