Persistence of Mixed Cryoglobulinemia Despite Cure of Chronic Hepatitis C With Oral Direct Acting Antiviral Therapy: A Case Series

Abstract

Introduction: Patients with chronic hepatitis C (HCV) are at increased risk for liver-related complications. Obtaining a sustained virologic response can decrease these complications and be curative. Roughly 40% of patients with chronic HCV will develop an extrahepatic manifestation of their disease. A concerning complication is mixed cryoglobulinemia (MCN), which, in its most severe form, presents as glomerulonephritis or an aggressive vasculitis. There is a paucity of data showing the effective clearance of cryoglobulins with the addition of direct acting antiviral drugs. We report a case series of 5 patients with genotype one chronic HCV complicated by MCN, who had persistence of cryoglobulins despite completion of triple therapy with direct acting oral antiviral agents (DAA) (boceprivir, telaprivir, or sofosbuvir). Please see Table 1 for a summary about treatment outcomes. Patients with cirrhosis seemed to have a decreased ability to clear immune complexes. 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. 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 Bcell agent rituximab prior to starting therapy for HCV; this did not lead to a more effective clearance of cryoglobulins. More studies to determine the ideal duration of treatment for chronic HCV and coincident MCN are needed. Early virologic response in patients without cirrhosis corresponds to cryoglobulin clearance. Patients with cirrhosis and cryoglobulins should be considered for extended therapy duration.Table 1: Patient characteristics