High Prevalence of Serum Cryoglobulins in Multitransfused Hemophilic Patients With Chronic Hepatitis C

The prevalence, clinical relevance, and risk factors of serum cryoglobulins in hemophilic patients with chronic hepatitis C virus (HCV) infection are unknown. We studied 135 consecutive hemophilic patients (median age, 31 years; range, 10 to 69 years) with chronic hepatitis C, exposed to the virus for 10 to 41 years. A total of 67 patients were coinfected with the human immunodeficiency virus (HIV), and 3 (2%) had signs of cirrhosis. Serum samples were tested for the presence of cryoglobulins, hepatitis B virus (HBV) markers, including HBV-DNA by hybridization assay, and antibody to HCV by enzyme immunoassay (EIA). Serum HCV-RNA was tested by polymerase chain reaction and typed with a hybridization technique. Samples were also tested for antitissue antibodies, immunoglobulins, rheumatoid factor, and C3 and C4 proteins of complement. Forty-two hemophiliacs (31%) circulated cryoglobulins (median levels, 166 mg/L; range, 66 to 480) predominantly type III (62%; and 29% type II). None of the patients had clinical signs or symptoms of systemic vasculitis. Cryoglobulinemic patients had more often serum HCV-RNA (95% v 80%, P < .05), rheumatoid factor (20% v 6%, P < .05), higher levels of IgG (2,354 ± 682 mg/dL v 1,928 ± 557 mg/dL,P < .0005) and IgM (323 ± 226 mg/dL v 244 ± 243 mg/dL, P < .05), and lower levels of serum C4 (19 ± 8 mg/dL v 24 ± 8 mg/dL, P < .05) than patients without cryoglobulins. The risk of producing cryoglobulins was greater for 114 patients circulating HCV-RNA than for 21 nonviremic patients (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.1 to 22.0) and for the 31 patients with longer exposure to HCV (more than 26 years) than for the 24 patients with shorter (17 years or less) exposure (OR = 4.4 95% CI = 1.1 to 18.0). In conclusion a large number of multitransfused hemophiliacs with chronic HCV infection circulated serum cryoglobulins but none had clinical signs or symptoms of vasculitis. The risk of developing cryoglobulins parallels the duration of exposure to HCV.