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HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45–70%), antinuclear (10–40%) and anticardiolipin (15–20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.