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

Abstract

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.

Keywords: Cryoglobulinemia; Depression; Liver disease; Quality of life; Vasculitis.

Fig. 1

Average scores of the psychometric scales and of the synthetic indexes of the Short Form-36 questionnaire, PCS and MCS, for the entire population over time. Panel A HAM-D mean values; panel B HAM-A mean values; panel C MADRS mean values; panel D MRS mean values; panel E PCS mean scores; panel F MCS mean scores; ^* = p ≤ 0.05, ^** = p ≤ 0.01, ^*** = p ≤ 0.001, **** = p ≤ 0.0001. Abbreviations: HAM-D (Hamilton Rating Scale for Depression), HAM-A (Hamilton Rating Scale for Anxiety); MADRS (Montgomery-Asberg Depression Rating Scale); MRS (Mania Rating Scale); PCS (Physical Component Summary); MCS (Mental Component Summary; W0 (Week 0); W4 (Week 4); EOT (End of Treatment); SVR12 (Sustained Virological Response 12 weeks)

Fig. 2

Average scores of the psychometric scale and of the synthetic indexes of the Short Form-36 questionnaire, PCS and MCS, for CV subgroup over time. Panel A HAM-D mean values; panel B HAM-A mean values; panel C MADRS mean values; panel D MRS mean values; panel E PCS mean scores; panel F MCS mean scores; ^* = p ≤ 0.05, ** = p ≤ 0.01, *** = p ≤ 0.001. Abbreviations: CV, cryoglobulinemic vasculitis; HAM-D, Hamilton Rating Scale for Depression; HAM-A, Hamilton Rating Scale for Anxiety; MADRS, Montgomery-Asberg Depression Rating Scale; MRS, Mania Rating Scale; PCS, Physical Component Summary; MCS, Mental Component Summary; W0, week 0; W4, week 4; EOT, end of treatment; SVR12, sustained virological response 12 weeks)

Fig. 3

Average scores of the psychometric scale and of the synthetic indexes of the Short Form-36 questionnaire, PCS and MCS, for NON-CV subgroup over time. Panel A HAM-D mean values; panel B HAM-A mean values; panel C MADRS mean values; panel D MRS mean values; panel E PCS mean scores; panel F MCS mean scores; * = p ≤ 0.05, ** = p ≤ 0.01, *** = p ≤ 0.001. Abbreviations: NON-CV, non-cryoglobulinemic vasculitis; HAM-D, Hamilton Rating Scale for Depression; HAM-A, Hamilton Rating Scale for Anxiety; MADRS, Montgomery-Asberg Depression Rating Scale; MRS, Mania Rating Scale; PCS, Physical Component Summary; MCS, Mental Component Summary; W0, week 0; W4, week 4; EOT, end of treatment; SVR12, sustained virological response 12 weeks

Fig. 4

Comparison of the mean scores of the psychometric scales and of the synthetic indexes of the Short Form-36 questionnaire, PCS and MCS, between the CV and NON-CV subgroups for each time-points. CV vs NON-CV mean score resulting from the four psychometric scales and from the summary scores of SF-36; row W0: week 0 analysis; row B W4: week 4 analysis; row EOT: End Of Treatment analysis; row SVR12: Sustained Virological Response 12 weeks analysis. ** = p ≤ 0.01, *** = p ≤ 0.001, **** = p ≤ 0.0001. Abbreviations: CV, cryoglobulinemic vasculitis; NON-CV, non-cryoglobulinemic vasculitis; SF-36, Short Form-36 questionnaire; HAM-D, Hamilton Rating Scale for Depression; HAM-A, Hamilton Rating Scale for Anxiety; MADRS, Montgomery-Asberg Depression Rating Scale; MRS, Mania Rating Scale; PCS, Physical Component Summary; MCS, Mental Component Summary