title: PegIFNα/ribavirin/protease inhibitor combination in severe hepatitis C virus-associated mixed cryoglobulinemia vasculitis.
abstract: OBJECTIVE
  The aim of this study was to analyse the safety and efficacy of the PegIFNα/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis.
  
  
  METHODS
  This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNα/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]).
  
  
  RESULTS
  Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021).
  
  
  CONCLUSIONS
  The PegIFNα/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions.
authors.affiliation: Department of Internal Medicine and Clinical Immunology, AP-HP, Hôpital Pitié-Salpétrière, DHU I2B, Immunopathology, Inflammation, Biotherapy, Paris, France; Université Pierre et Marie Curie, Paris VI, UMR CNRS 7211, INSERM U959, Hôpital Pitié-Salpétrière, Paris, France. Electronic address: david.saadoun@psl.aphp.fr.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.affiliation: Department of Biostatistics, Hôpital Saint-Louis, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Resche Rigon
authors.affiliation: Department of Hepatology, Hôpital Necker, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Department of Virology, Hôpital Pitié-Salpétrière, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.affiliation: Department of Internal Medicine, Hôpital Lapeyronie, Montpellier, France.
authors.forename: François
authors.initials: F
authors.lastname: Blanc
authors.affiliation: Department of Infectious Diseases, Hôpital Tenon, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: Department of Nephrology, Hôpital Européen George Pompidou, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.affiliation: Department of Nephrology, Hôpital de la Robertsau, Strasbourg, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Bazin-Kara
authors.affiliation: Department of Internal Medicine, Centre Hospitalier de Nouvelle Calédonie, Nouméa, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazorla
authors.affiliation: Department of Infectious Diseases, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vittecoq
authors.affiliation: Laboratory of Immunochemistry, Hôpital Pitié-Salpétrière, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Department of Nephrology, Hôpital Tenon, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Peltier
authors.affiliation: Department of Internal Medicine, Hôpital Sud, Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Decaux
authors.affiliation: Department of Internal Medicine, Hôpital Croix Saint Simon, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ziza
authors.affiliation: Department of Internal Medicine, Hôpital Bicêtre, Kremlin Bicêtre, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.affiliation: Department of Internal Medicine and Clinical Immunology, AP-HP, Hôpital Pitié-Salpétrière, DHU I2B, Immunopathology, Inflammation, Biotherapy, Paris, France; Université Pierre et Marie Curie, Paris VI, UMR CNRS 7211, INSERM U959, Hôpital Pitié-Salpétrière, Paris, France. Electronic address: patrice.cacoub@psl.aphp.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D003449:Cryoglobulinemia / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; 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; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014657:Vasculitis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: Antiviral treatment; Hepatitis C virus; Mixed cryoglobulinemia; Treatment; Vasculitis