AIM:To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor alpha (TNF-alpha) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV). METHODS:Serum NTproBNP and TNF-alpha levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls. RESULTS:Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-alpha levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (c2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (c2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (c2, P = 0.08). CONCLUSION:The study demonstrates high levels of circulating NTproBNP and TNF-alpha in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.