BACKGROUND: Mixed cryoglobulin is usually associated with hepatitis C virus (HCV) infection and might cause systemic vasculitis. The presence and impact of cryofibrinogen, another cryoprotein, in the serum of HCV-infected patients have not yet been evaluated. The objective was to study the prevalence and the clinical and therapeutic impacts of cryofibrinogen in HCV-infected patients. METHODS: A total of 143 consecutive HCV-infected (RNA+) patients (including 57 patients with HCV-related vasculitis) were screened for cryofibrinogen and cryoglobulin (positive if >0.05 g/L). The main characteristics and outcome were evaluated according to the cryofibrinogen/cryoglobulin status at baseline. RESULTS: At baseline, 53 of 143 patients (37%) were cryofibrinogen positive, most of whom (47/53 [89%]) were also cryoglobulin positive. Only 37 of 90 cryofibrinogen-negative patients (41%) were cryoglobulin positive (P<.001). In patients with HCV-related vasculitis, 28 of 57 (49%) were cryofibrinogen positive compared with 25 of 86 patients (29%) without vasculitis (P=.03). There was a higher rate of renal involvement in cryofibrinogen-negative/cryoglobulin-positive patients than in cryofibrinogen-positive/cryoglobulin-positive patients (10/25 [40%] vs 3/27 [11%], respectively; P=.02). After a mean follow-up of 32.6 months, among patients who were cryofibrinogen positive at baseline, 12 of 26 (46%) of those who received an HCV treatment were cryofibrinogen negative at the end of follow-up compared with 4 of 16 (25%) of those who did not receive antiviral drugs. Most patients who became cryofibrinogen negative also became cryoglobulin negative (93%). CONCLUSION: Cryoproteins, including cryoglobulin and cryofibrinogen, are frequently found in the serum of HCV-infected patients. In such patients, a positive cryofibrinogen status is closely related to the presence of cryoglobulin at baseline and after antiviral therapy.