ObjectivesTo investigate the clinical and serological features of autoimmunity with chronic hepatitis C virus infection before and after direct-acting antiviral therapy and assess their relation to treatment response.MethodsA prospective cohort study was performed in adult patients aged ≥18 years who had chronic hepatitis C virus infection, as confirmed by polymerase chain reaction, and were eligible for direct-acting antiviral therapy. Patients with rheumatological disease prior to the onset of hepatitis C virus infection, decompensated cirrhosis, or hepatocellular carcinoma were excluded. All patients were treated with sofosbuvir (400 mg once daily) plus daclatasvir (60 mg once daily) for 3 months. Patients were assessed before and 12 weeks after treatment.ResultsNinety patients completed the follow-up (66.7% females, 33.3% males, mean age: 49.2 ± 12.3 years); 85.55% of them had immune-mediated manifestations prior to direct-acting antiviral therapy. In patients with sustained virologic response, autoimmune manifestations persisted in 66 of the 71 (92.9%) patients with an observable rise in posttreatment erythrocyte sedimentation rate and C-reactive protein level (p > 0.01). The predictors of persistence of autoimmune manifestation were age ≥49 years (p = 0.009), female sex (p = 0.026), and tobacco use (p = 0.043).ConclusionDirect-acting antiviral drugs were not associated with a significant short-term change in the prevalence of autoimmune manifestations in patients who had hepatitis C virus infection with sustained virologic response.