Achieving Sustained Viral Remission in Patients with Chronic HCV Infection and Cryoglobulinemic Vasculitis Does Not Always Correlate with Normalization of the Serologic Markers.

Objective: We aim to describe the persistence of symptoms associated with HCV-associated cryoglobulinemic vasculitis following achievement of (SVR) with IFN- free direct acting antiviral (DAA) therapy. In particular, we describe the persistence of C4 hypocomplementemia and positive Rheumatoid Factor (RF).

Methods: We analyzed a case series of four patients enrolled from the Cleveland VA and known to have chronic HCV infection complicated by mixed cryoglobulinemia. The study included patients treated with interferon (IFN) based treatment and IFN free direct acting antiviral (DAA) therapy.

Results: Of the four patients, patients 1 and 2 experienced decline of RF without resolution following DAA therapy. Patient 1 continues to have evidence of disease following treatment. Patient 3 did not have resolution of RF during IFN-based treatment and experienced stabilization of kidney function while on treatment. Patient 4, previously a non-responder to IFN based treatment, experienced significant decline in RF titers along with resolution of cryoglobulin-associated rash with DAA therapy. C4 remained low following treatment in patients 1 and 3. Of the four patients, only patient 1 had prolonged persistence of cryoglobulinemia, measured at 3%, 17 months following achievement of SVR.

Conclusions: We highlight the complexity of the viral-mediated immunologic mechanism that causes cryoglobulinemic vasculitis. Our cases also emphasize the need to consider cryoglobulinemic vasculitis as part of the differential diagnosis even with treated HCV infection. Recognizing these findings are important in our understanding of the pathophysiology of the disease and management in the era of IFN-free DAA therapy.