Clinical relevance of serum non-organ-specific antibodies in patients with HCV infection receiving direct-acting antiviral therapy

Background: Hepatitis C virus (HCV) infection is associated with production of different serum non-organ-specific antibodies (NOSA) and risk for developing autoimmune disorders. The clinical significance of these phenomena is not fully understood. Aim: To assess non-organ-specific antibodies before and 24 weeks after the end of therapy with direct-acting antivirals in patients with HCV-related infection, to better clarify the clinical relevance of these antibodies in terms of treatment response and prognostic value. Methods: Patients enrolled (191) were considered non-organ-specific antibody-positive for titres ≥1:40 on at least two determinations before treatment. Results: At baseline, 46 patients were positive and 145 were negative for autoantibodies. The prevalence of autoimmune thyroiditis was significantly higher in non-organ-specific antibody-positive group than non-organ-specific antibody-negative group (P = 0.02). HCV-RNA 24 weeks after the end of antiviral therapy was 100% negative in patients with antibodies positivity and 98.6% in antibody-negative patients (P = 1.0). In the former group, autoantibodies disappeared in 30 of 46 patients (65.2%). On multivariate analysis, non-organ-specific antibody-negativity was significantly reduced in patients with hepatic hilar lymphadenopathy (OR = 0.17; 95% CI 0.02-0.94, P = 0.04). None of the adverse events occurring during antiviral therapy was related to autoimmune disorders. Conclusions: Hepatitis C virus clearance frequently reduces non-organ-specific antibody positivity suggesting that they represent an epiphenomenon of the viral infection. However, in patients who did not become negative, long-term monitoring would establish whether they could hide an underlying process that may progress into a clear autoimmune or rheumatologic disease. (Trial registration number: NCT03566966).