A prospective study of direct-acting antiviral effectiveness and Relapse Risk in HCV Cryoglobulinemic Vasculitis by the Italian PITER Cohort

Background & aims: Mixed cryoglobulinemia (MC) is the most common Hepatitis C Virus (HCV) extrahepatic manifestation. We aimed to prospectively evaluate the Cryoglobulinemic Vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-long term period. Approach: Direct Acting Antiviral (DAA) treated cryoglobulinemic patients, consecutively enrolled in the multicentric PITER cohort, were prospectively evaluated. Cumulative incidence, Kaplan Meier curves were reported for response, clinical deterioration or relapse and survival free rates. Cox regression analysis evaluated factors associated with different outcomes. Results: A clinical response was reported in at least one follow-up point for 373 of 423 (88%) CV patients who achieved a SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A Full Complete Response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration: 19 months). In patients who achieved a FCR and had an available follow-up (137 patients) a relapse was observed in 13%; it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving a SVR, a clinical non-response was associated with age and renal involvement; a clinical deterioration/relapse was associated with high pre-treatment rheumatoid factor values and a FCR was inversely associated with age, neuropathy, and high cryocrit levels. Conclusions: In CV patients, HCV eradication may not correspond to a persistent clinical improvement and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.