Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia

Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis commonly regresses upon virus eradication, butconv en tio nal the rapy with pegylated interferon and ribavirin yields approximately 40% sustained virologic respo ns es (SVR).We prospectively evaluated the efficacy and safety of sofosbuvir-based direct-acting antiviral therapy, individually tailoredaccording to the latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC. In two patients MC hadevolved into an indolent lymphoma with monoclonal B-cell lymphocytosis. All patients had negative HCV viremia at week 12(SVR12) and at week 24 (SVR24) posttreatment, at which time all had a clinical response of vasculitis. The mean (6standarddeviation) Birmingham Vasculitis Activity Score decreased from 5.41 (63.53) at baselin e to 2.35 (62.25) (P < 0.001) at week4 on treatment to 1.39 (61.48) (P < 0.001) at SVR12 and to 1.27 (61.68) (P < 0.001) at SVR24. The mean cryocrit valuefell from 7.2 (615.4)% at baseline to 2.9 (67.4)% (P < 0.01) at SV R12 and to 1.8 (65.1)% (P < 0.001) at SVR24. Intr ig u-ingly, in the 2 patients with MC and lymphoma there was a partial clinical response of vasculitis and 50% decrease of cryo-crit, although none experienced a significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred in 59% ofpatients and were generally mild, with the exception of 1 patient with ribavirin-related anemia requiring blood transfusion.Conclusion: 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 per-spective for curing the large majority of these so far difficult-to-treat patients. (HEPATOLOGY 2016;64:1473-1482)