title: Triple antiviral therapy in hepatitis C virus infection with or without mixed cryoglobulinaemia: a prospective, controlled pilot study.
abstract: BACKGROUND
  Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease.
  
  
  METHODS
  Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy.
  
  
  RESULTS
  In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p=0.01).
  
  
  CONCLUSIONS
  Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia.
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, 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, 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, Florence, Italy.
authors: Elisa
authors: E
authors: Triboli
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, 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, Florence, Italy.
authors: Barbara
authors: B
authors: Boldrini
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, 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, 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, Florence, Italy.
authors: Patrizio
authors: P
authors: Caini
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, 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, 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, Florence, Italy.
authors: Giacomo
authors: G
authors: Laffi
authors: Center for Systemic Manifestations of Hepatitis Viruses (MASVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address: a.zignego@dmi.unifi.it.
authors: Anna Linda
authors: AL
authors: Zignego
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000150:complications*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C100416:peginterferon alfa-2a
keywords: Antiviral therapy; Direct-acting antiviral; Hepatitis C virus; Mixed cryoglobulinaemia