Treatment of hepatitis C virus–associated mixed cryoglobulinemia with direct‐acting antiviral agents

Abstract

Background Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral directly-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. Methods Case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single healthcare network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (N=7) was established by kidney biopsy (N=5) or by ≥ 2 of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (N=2). Results Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% male, 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7 – 2.47 mg/dL.) Four patients received Rituximab concurrent with DAA therapy. Sustained virological response rate at twelve weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5%, and completely disappearing in 4 of 9 cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12 rate with 100% experiencing at least one adverse event, and 50% experiencing premature discontinuation due to adverse events. Conclusion SVR12 rates for sofosbuvir-based direct acting antiviral regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin. Patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis

“…Sustained virological response is the main goal in these patients since clinical remission of vasculitis is closely associated with viral clearance 8 . Few studies have reported promising results on the effectiveness and tolerance of direct acting antiviral drugs (DAA), either in association with interferon (IFN) or using IFN-free regimens [8][9][10][11] . The aim of the present study was to evaluate effectiveness and tolerance of an all oral IFN-and ribavirin-free regimen with sofosbuvir plus daclatasvir in patients with cryoglobulinemia vasculitis.…”

Editorial: Benefit of Direct-Acting Antiviral Therapy For Cryoglobulinemia due to Hepatitis C Infection

“…For at least some patients with severe cryoglobulinemia achievement of SVR may be insuffi cient to complete mitigate its manifestations, and additional support with rituximab and/or plasmapheresis may still be required. However, this report and others indicate that inferior SVR rates in HCV patients with cryoglobulinemia have been overcome with DAA therapy ( 8,9 ), and that clinical improvement, although not inevitable, typically follows. Th e enhanced effi cacy of DAA has simplifi ed management of this important manifestation of HCV infection.…”

Hepatitis C Virus Diagnosis in Prospective Blood Donors: Epidemiology, Optimal Testing Approach and Treatment Cut-offs

“…patients with decompensated cirrhosis, renal impairment, HIV/HCV or HBV/HCV co-infections and those who develop recurrent HCV infection following liver transplantation) and pre-treatment assessment of patient's understanding of the goals of therapy as well as the need for adherence and follow up. Studies have shown that reduction in severity of disease and eventual cure for HCV contribute to dramatic reduction in all-cause mortality (including hepatic decompensation events, hepatocellular carcinoma and liver-related mortality) and improve quality of life [61][62][63][64][65][66] . Dhawan documented various drug regimens for the treatment of hepatitis C [67] .…”