title: Virological and Clinical Response to Interferon-Free Regimens in Patients with HCV-Related Mixed Cryoglobulinemia: Preliminary Results of a Prospective Pilot Study.
abstract: Mixed Cryoglobulinemia (MC) is the most frequent extrahepatic manifestation of Hepatitis C virus (HCV) infection. MC is an autoimmune /B-cell lymphoproliferative disorder characterized by circulating immune-complexes, named cryoglobulins. MC patients exhibit symptoms due to a systemic vasculitis of small/medium size vessels (mixed cryoglobulinemia syndrome, MCS) in a percentage going from 5 to 30%. The first-line therapeutic option in MCS patients is the etiologic treatment and, in the past fifteen years, antiviral therapy with Pegylated-Interferon (Peg-IFN) plus Ribavirin (RBV) represented the standard of care. Lately, the arrival of direct acting antivirals (DAAs) significantly modified the cure of HCV infection, consenting the use of IFN-free regimens. Here we report a review of the literature about the role of antiviral treatment, following its evolution, in treating HCVrelated MC. Furthermore, we report the results, after 8 weeks of treatment, of a preliminary pilot prospective study, counting 17 patients with HCV-related MC with or without MCS, treated with new generation DAAs in IFN-free regimens. After 8 weeks of DAA administration, all the subjects were HCV RNA negative. Moreover, in 6/17 (35%) patients cryoglobulins disappeared and, on the whole, in all patients a decrease of the cryocrit values was observed (p&lt;0.05). Furthermore, three MCS-HCV patients (30%) resulted to be complete clinical responders and 5 subjects (50%) partial clinical responders. Therefore, IFN-free anti-HCV treatment appears to be safe and effective in MC patients from virological and clinical points of view, thus supporting the importance of HCV eradication in leading MC remission.
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Laura
authors: L
authors: Gragnani
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Alessia
authors: A
authors: Piluso
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Teresa
authors: T
authors: Urraro
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Alessio
authors: A
authors: Fabbrizzi
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Elisa
authors: E
authors: Fognani
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Luisa
authors: L
authors: Petraccia
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Alessandro
authors: A
authors: Genovesi
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Lidia
authors: L
authors: Giubilei
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Jessica
authors: J
authors: Ranieri
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Cristina
authors: C
authors: Stasi
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Monica
authors: M
authors: Monti
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, largo Brambilla, 3, 50134- Florence, Italy.
authors: Anna Linda
authors: AL
authors: Zignego
mesh_terms: D000368:Aged; D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000821:virology*; D003521:Cyclopropanes; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011392:Proline / Q000031:analogs & derivatives; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology; D013449:Sulfonamides; D016896:Treatment Outcome; D014633:Valine
chemical_list: D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D012367:RNA, Viral; D013449:Sulfonamides; C586094:ombitasvir; D011392:Proline; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir
keywords: Antiviral treatment; HCV; direct-acting antiviral (DAA); efficacy; interferon-free (IFN-free); mixed cryoglobulinemia; safety