Objective. Obtaining a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) can decrease hepatic complications and be curative, however, extrahepatic manifestations including mixed cryoglobulinemia (MCN) may persist with interferon-based therapy. Our objective was to review our experience in treating patients with new oral antiviral agents and to assess common factors associated with MCN persistence despite SVR. Methods. We analyzed a case series of five patients with genotype one chronic HCV complicated by MCN who had persistence of cryoglobulins despite completion of triple therapy with oral antiviral agents (boceprivir, telaprivir or sofosbuvir). Results. Patients with cirrhosis appear to have a decreased ability to clear immune complexes. We observed that early viral response by week 8 of therapy and longer periods of undetectable virus on treatment correlated with eventual clearance of serum cryoglobulins in patients without cirrhosis. Two patients were treated with anti-B-cell agent rituximab prior to starting therapy for HCV; this did not lead to a more effective clearance of cryoglobulins. Conclusions. We suggest that a longer treatment course than the standard 24 weeks with triple therapy could aid in the clearance of these immune complexes and cryoglobulins in cirrhotics. More studies to determine the ideal duration of treatment for chronic HCV and coincident MCN are needed, especially in light of the new all oral direct-acting antiviral regimens that are now recommended for HCV treatment.
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