Hepatitis C virus (HCV) infection is a significant cause of hepatic and extrahepatic manifestations. Direct-acting antiviral (DAAs) therapies proved highly effective in treating HCV. This study aimed to assess the autoimmune serological progression of asymptomatic Egyptian patients with chronic HCV after treatment with DAAs. Methods: Twenty patients with chronic HCV with exclusion of any rheumatic clinical manifestations were treated with sofosbuvir 400 mg and daclatasvir 60 mg for three months. This study evaluated the autoimmune serological progression in these patients. Results: All the 20-patients achieved sustained viral response (SVR), and none of them had clinical autoimmune manifestations. We found reduction in the number of positive cryoglobulins (15% before treatment and all became negative after treatment). There was no significant improvement in rheumatoid factor (RF) (25% before versus 20% after treatment) or Immunoglobulin-G (IgG) (25% before versus 20% after treatment), (P values ˂0.293 and ˂0.794 respectively). No significant improvement in Immunoglobulin-M (IgM) and Immunoglobulin-A (IgA) was observed (P values 0.097 and 0.538 respectively). We didn’t find reduction in numbers of patients with positive antinuclear antibodies (ANA). No marked changes in Anti-Ro, Anti-La antibodies, complement 3 (C3) and complement 4 (C4) after SVR. Conclusion: HCV clearance by DAAs is accompanied with autoantibody changes. Nevertheless, most of the patients endure autoantibody-positivity; also some patients were negative before treatment and acquired autoantibodies following SVR. These findings prove that HCV is linked to autoimmunity and reveal that its autoimmune impact continues despite viral clearance by DAAs, implying that long-term monitoring is necessary