title: Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia.
abstract: Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, but conventional therapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir-based direct-acting antiviral therapy, individually tailored according to the latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC. In two patients MC had evolved into an indolent lymphoma with monoclonal B-cell lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (±standard deviation) Birmingham Vasculitis Activity Score decreased from 5.41 (±3.53) at baseline to 2.35 (±2.25) (P < 0.001) at week 4 on treatment to 1.39 (±1.48) (P < 0.001) at SVR12 and to 1.27 (±1.68) (P < 0.001) at SVR24. The mean cryocrit value fell from 7.2 (±15.4)% at baseline to 2.9 (±7.4)% (P < 0.01) at SVR12 and to 1.8 (±5.1)% (P < 0.001) at SVR24. Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and ∼50% decrease of cryocrit, although none experienced a significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred in 59% of patients and were generally mild, with the exception of 1 patient with ribavirin-related anemia requiring blood transfusion.
  
  
  
  Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gragnani
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fognani
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Urraro
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: De Santis
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Petraccia
authors.affiliation: Istituto Dermopatico Dell'Immacolata IRCCS, Rome, Italy.
authors.forename: Marie
authors.initials: M
authors.lastname: Perez
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Ceccotti
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Colantuono
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Milica
authors.initials: M
authors.lastname: Mitrevski
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Stasi
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Del Padre
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gianni
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
authors.affiliation: Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. a.zignego@dmi.unifi.it.
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000821:virology*; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D012254:Ribavirin; D000069474:Sofosbuvir / Q000627:therapeutic use*; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy* / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069474:Sofosbuvir