The dilemma of treating hepatitis C virus-associated cryoglobulinemia

The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with direct-acting antiviral agents (DAAs).

Hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients with mixed cryoglobulinemia syndrome. Clinical research has been focused on antiviral drugs and, more recently, on the new, highly potent DAAs. New DAAs assure sustained virologic response (SVR) rates greater than 90% with relief of mild-to-moderate symptoms.

Mixed cryoglobulinemia may present with multiorgan vasculitis involving kidneys, joints, skin, and peripheral nerves. Data on DAAs efficacy in HCV-associated cryoglobulinemic vasculitis are disappointing possibly because of the inability of these drugs to suppress the immune-mediated process once it has been triggered. Immunosuppression has often been employed in the past as a first-line therapy in cryoglobulinemic vasculitis despite the potential risk of the infection exacerbation. However, more manageable Rituximab-based therapeutic approaches have been more recently used without increase of viral load. Rituximab substantially changed the outcome of HCV-associated cryoglobulinemic vasculitis by providing long-term remission. A combination schedule of DAAs and Rituximab may result in eradication of both cryoglobulinemic vasculitis and HCV infection.