Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).

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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.

No significant differences in SVR rates were recorded between cryoglobulinaemic patients and controls and a high clinical and immunological efficacy was confirmed in CV, supporting the role of interferon-free therapy as the first therapeutic option. Interestingly, CV patients had worse baseline QoL than other HCV-positive groups and interferon-free therapy was effective in significantly increasing QoL, suggesting the important role of direct-acting anti-viral-based therapy in improving CV's individual and social burden.

Mud-bath therapy plays a primary role in the treatment and prevention of osteoarthritis that has been recognised since antiquity. Numerous studies have demonstrated its clinical benefits and its effects on inflammatory mediators (interleukins), the immune system, cenesthesic factors (endorphins), and the diencephalic–pituitary–adrenal axis. This study was conducted to assess the efficacy of mud-bath therapy with mineral water from the Sillene Spring at Italy’s Chianciano Spa in patients with osteoarthritis of the knee. Patients (n = 61) were divided into two groups. Group A underwent three cycles of mud-based spa therapy over a year’s time, whereas group B did not. Clinical conditions, visual analogue scale pain ratings, and Lequesne indexes of the two groups were compared. We also compared these same parameters in the patients of the two groups that were following the therapy with drugs and in the patients of the group A before and after spa treatment. The percentage of patients with no symptoms or mild symptoms was higher in group A than in group B. Within group A, this percentage was higher after treatment than before spa therapy. Even in the comparison between the patients of the two groups that were following the therapy with drug, the results was that in group A the percentage of patients with no symptoms or mild symptoms was higher than in group B. Statistical analyses based on various tests revealed that almost all these differences were highly significant. No adverse effects were observed in any of the patients in group A. In conclusion, the mud-bath therapy performed at Chianciano Spa with Sillene Spring water remarkably improved the clinical conditions of patients with knee arthritis and significantly reduces the frequency and severity of symptoms and the disability they cause.