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 1 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 5 0.009) and MC-HCV1MCS-HCV (P 5 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. Conclusion: 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. (HEPATOLOGY 2015;61:1145-1153 M ixed cryoglobulinemia (MC) is an autoimmune/lymphoproliferative disorder characterized by circulating immune complexes named cryoglobulins (CGs) that reversibly precipitate at low temperatures. The CGs are comprised of polyclonal immunoglobulin Gs (including anti-hepatitis C virus [HCV] immunoglobulin) and mono-or polyclonal immunoglobulin M with rheumatoid factor activity, sustained by the clonal expansion of rheumatoid factor B cells.

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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<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.

Objective. Mixed cryoglobulinemia (MC) is a hepatitis C virus (HCV)-Conclusion. These results indicate the importance of host genetic background in the development of HCV-MC, suggesting that mechanisms enhancing Ig production and B cell survival may play a relevant role. Genetic Fc␥R variants seem to be crucial to the effectiveness of rituximab therapy.

This study aimed to investigate the emotional impact of technology use in an Italian adult population and to detect technophobia. This cross-sectional study was conducted with 117 Italian participants (age range of 50–67 years). Measured variables were computer anxiety and technology use ability. The results revealed technophobia features in the Italian adult population related to inadequate management of technology. One-way analysis of variance and Bonferroni’s post-hoc analysis showed that non-autonomous (p < 0.01), low-frequency (p < 0.01), and feeling-a-need-for-help users (p < 0.01) had higher levels of computer anxiety. Based on our data, although lifelong learning is a powerful digital need, a considerable proportion of the adult population is not digitally skilled, enlarging the gap between young (native digital) and adult (digital and non-digital adults and seniors) populations. Adult inclusivity in digital living is inadequate and likely affects their quality of life. Thus, our findings highlight technophobia as a possible new risk factor for Italian adults because it can affect their daily life through low adherence to digital living; rather than aging successfully, they could develop fragile aging.