Mixed cryoglobulinemia (MC) is a pre-lymphomatous autoimmune/lymphoproliferative disorder (LPD) strictly related to HCV infection. MC symptoms are due to a systemic vasculitis of small/medium vessels (MC syndrome-MCS). Treatment with PegIFN+RBV have been indicated as the first option for mild/ moderate HCV+MCS. However, limited data are available concerning the long-term effects of HCV eradication on the natural history of MC/MCS and the virological response of these patients compared to HCV patients without MC. 424 consecutive Caucasian HCV patients (226 males) were prospectively included in three different cohorts: (a) 121 patients with MCS-HCV (76 males); (b) 132 patients with circulating cryoglobulins but without MCS (MC-HCV) (64 males); (c) 158 patients without MCS (112 males) (HCV). Thirteen patients were excluded for uncertain classification. In all patients Peg-IF-N+RBV treatment was administered according to standard protocols. Patients were evaluated for both main hepato-virological and clinical-immunological data every three months during treatment and six months during follow-up. The clinical-immunological efficacy in MCS patients was evaluated as previously described. Briefly, a complete clinical response was defined as improvement in all baseline clinical manifestations and a partial clinical response as improvement in at least half of the baseline symptoms. All the other patients were classified as clinical non-responders. According to Intention To Treat analysis, a significant difference was observed in sustained virological response (SVR) rates between HCV and MC-HCV patients (61.4% and 45.5% respectively, p=0.009), and between HCV and MC-HCV+MCS-HCV (61.4% and 48.6% respectively, p=0.014). The multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of non-response to antiviral therapy. This was obtained considering only MCS (O.R. 2.25; 95%CI 1.07-4.73; p=0.03) and MC+MCS (O.R. 2.02; 95%CI 1.12-3.68; p=0.02). The clinical-immunological response in MCS was strictly related to the virological one; all but 2 MCS SVR patients experienced a complete clinical response in the follow-up (30-120 months). In conclusion, this study, for the first time, evaluated the long-term effects of viral eradication on HCV MC patients and pro-spectively compared the effects of IFN-based therapy on HCV patients with MCS, with only laboratory MC and without MC. This study showed that MC represents a negative prognostic factor for viral eradication and that HCV eradication may allow persistent resolution or consistent improvement of MCS, strongly suggesting the interest for the next generation of antiviral drugs.

Response to IFN-based antiviral therapy and long term effect of HCV eradication in Mixed Cryoglobulinemia, with or without symptoms: a prospective, controlled, open-label, long term, cohort study

Gragnani L;
2014-01-01

Abstract

Mixed cryoglobulinemia (MC) is a pre-lymphomatous autoimmune/lymphoproliferative disorder (LPD) strictly related to HCV infection. MC symptoms are due to a systemic vasculitis of small/medium vessels (MC syndrome-MCS). Treatment with PegIFN+RBV have been indicated as the first option for mild/ moderate HCV+MCS. However, limited data are available concerning the long-term effects of HCV eradication on the natural history of MC/MCS and the virological response of these patients compared to HCV patients without MC. 424 consecutive Caucasian HCV patients (226 males) were prospectively included in three different cohorts: (a) 121 patients with MCS-HCV (76 males); (b) 132 patients with circulating cryoglobulins but without MCS (MC-HCV) (64 males); (c) 158 patients without MCS (112 males) (HCV). Thirteen patients were excluded for uncertain classification. In all patients Peg-IF-N+RBV treatment was administered according to standard protocols. Patients were evaluated for both main hepato-virological and clinical-immunological data every three months during treatment and six months during follow-up. The clinical-immunological efficacy in MCS patients was evaluated as previously described. Briefly, a complete clinical response was defined as improvement in all baseline clinical manifestations and a partial clinical response as improvement in at least half of the baseline symptoms. All the other patients were classified as clinical non-responders. According to Intention To Treat analysis, a significant difference was observed in sustained virological response (SVR) rates between HCV and MC-HCV patients (61.4% and 45.5% respectively, p=0.009), and between HCV and MC-HCV+MCS-HCV (61.4% and 48.6% respectively, p=0.014). The multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of non-response to antiviral therapy. This was obtained considering only MCS (O.R. 2.25; 95%CI 1.07-4.73; p=0.03) and MC+MCS (O.R. 2.02; 95%CI 1.12-3.68; p=0.02). The clinical-immunological response in MCS was strictly related to the virological one; all but 2 MCS SVR patients experienced a complete clinical response in the follow-up (30-120 months). In conclusion, this study, for the first time, evaluated the long-term effects of viral eradication on HCV MC patients and pro-spectively compared the effects of IFN-based therapy on HCV patients with MCS, with only laboratory MC and without MC. This study showed that MC represents a negative prognostic factor for viral eradication and that HCV eradication may allow persistent resolution or consistent improvement of MCS, strongly suggesting the interest for the next generation of antiviral drugs.
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.27516
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1163431
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