The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents

Dario Roccatello _, Savino Sciascia, Daniela Rossi, Laura Solfietti, Roberta Fenoglio, Elisa Menegatti and Simone Baldovino

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Oncotarget. 2017; 8:41764-41777. https://doi.org/10.18632/oncotarget.16986

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Dario Roccatello1,2,*, Savino Sciascia1,2,*, Daniela Rossi1, Laura Solfietti1, Roberta Fenoglio2, Elisa Menegatti1 and Simone Baldovino1

1 Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy

2 Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy

* These authors have equally contributed to this manuscript

Correspondence to:

Dario Roccatello, email:

Keywords: mixed cryoglobulinemia, HCV-associated cryoglobulinemic vasculitis, HCV associated membranoproliferative glomerulonephritis, polyneuropathies, necrotizing skin ulcers

Received: October 07, 2016 Accepted: March 09, 2017 Published: April 09, 2017


Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.

Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.

The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.

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