title: Long-term effect of HCV eradication in patients with mixed cryoglobulinemia: a prospective, controlled, open-label, cohort study.
abstract: Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV(+) patients belonging to the following groups: MC syndrome (MCS)-HCV (121 patients with symptomatic MC), MC-HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow-up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC-HCV (P = 0.009) and MC-HCV+MCS-HCV (P = 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon-based therapy on HCV patients with and without MC and with and without symptoms, as well as the long-term effects of viral eradication on MC.
  
  
  CONCLUSIONS
  MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs.
authors.affiliation: 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.forename: Elisa
authors.initials: E
authors.lastname: Fognani
authors.forename: Alessia
authors.initials: A
authors.lastname: Piluso
authors.forename: Barbara
authors.initials: B
authors.lastname: Boldrini
authors.forename: Teresa
authors.initials: T
authors.lastname: Urraro
authors.forename: Alessio
authors.initials: A
authors.lastname: Fabbrizzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Stasi
authors.forename: Jessica
authors.initials: J
authors.lastname: Ranieri
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.forename: Umberto
authors.initials: U
authors.lastname: Arena
authors.forename: Claudio
authors.initials: C
authors.lastname: Iannacone
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003449:Cryoglobulinemia / Q000150:complications* / Q000821:virology*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a