Flow chart of therapeutic strategies according to activity/severity of mixed cryoglobulinemia (MC) syndrome (3). HCV-positive MC patients with moderate-severe manifestations, mainly in the presence of active chronic hepatitis, antiviral treatment with pegylated interferon-alpha (peg-IFN) + ribavirin (RIBA) can be tried after exclusion of possible contraindications. In non-responders or in those with partial response (virological), a treatment with rituximab (RTX) can be proposed (a). Conversely, in HCV+ MC patients usefully treated with rituximab or other anti- inflammatory/immunosuppressive therapies, an attempt to eradicate HCV infection can be done (b). Finally, combined high dose corticosteroids (CS), plasma exchange (PE), and cyclophosphamide (CPX) are the first line treatment in life-threatening, rapidly progressive complications in both HCV+ and HCV- cryoglobulinemic vasculitis (see also Fig. 8 and 9). LAC-diet: low-antigen-content diet.