Hepatitis C virus infection in patients with essential mixed cryoglobulinemia

Objective: To study the association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia. Setting: Wards and clinics of the Ospedali Riuniti di Bergamo and Ospedale di Treviglio e Caravaggio, Italy. Patients: Fifty-one patients with essential mixed cryoglobulinemia associated with glomerulonephritis and 45 controls with noncryoglobulinemic glomerulopathies. Measurements: Antibodies to hepatitis C virus (anti-HCV) in sera from patients with essential mixed cryoglobulinemia and from controls, using two enzyme-linked immunosorbent assays (c100 ELISA and c22/ c200 ELISA) and a recombinant immunoblot assay (4-RIBA); cryoprecipitate anti-HCV before and after use of dithiothreitol, a substance able to destroy IgM antibodies with rheumatoid factor activity, in patients with essential mixed cryoglobulinemia; serum HCV RNA by polymerase chain reaction in patients with essential mixed cryoglobulinemia. Results: In patients with essential mixed cryoglobulinemia, the c22/c200 ELISA detected anti-HCV in 98% of serum samples (95% Cl, 90% to 100%), whereas the rate of reactivity remained at 2% (Cl, 0% to 12%) in the control group (P < 0.0001). These results were confirmed by the 4-RIBA in 66% of patients with essential mixed cryoglobulinemia. The study of cryoprecipitate by c100 ELISA showed anti-HCV in 41% (Cl, 28% to 56%) of patients. After dithiothreitol, the rate of reactivity increased to 94% (Cl, 84% to 99%; P < 0.0001 by the McNemar paired chi-square test), suggesting that the elimination of rheumatoid factor leads to unmasking of anti-HCV in cryoprecipitate. Polymerase chain reaction detected HCV RNA in 13 of 16 sera from patients with essential mixed cryoglobulinemia. Conclusions: The extremely high prevalence of anti-HCV in serum and cryoprecipitate along with the frequently associated serum HCV RNA suggests a close relation between essential mixed cryoglobulinemia and chronic HCV infection.