title: Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents.
abstract: Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied 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 health care 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 two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine 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, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.
  
  
  CONCLUSIONS
  SVR12 rates for sofosbuvir-based DAA 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.
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Sise
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital.
authors.forename: Allyson K
authors.initials: AK
authors.lastname: Bloom
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wisocky
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Ming V
authors.initials: MV
authors.lastname: Lin
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Gustafson
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lundquist
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital.
authors.forename: David
authors.initials: D
authors.lastname: Steele
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital.
authors.forename: Michael
authors.initials: M
authors.lastname: Thiim
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital.
authors.forename: Winfred W
authors.initials: WW
authors.lastname: Williams
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Nikroo
authors.initials: N
authors.lastname: Hashemi
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000821:virology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D000069474:Sofosbuvir