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Visfatin is a new adipokine involved in several processes. The data concerning visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum concentration and to study its association with biochemical and morphological features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group 2), similar in age and BMI with normal fasting glucose and lipid profile were included. Visfatin was significantly increased in Group 1 compared with Group 2 (55.6 ± 23.1 vs 23.7 ± 3.8 ng/mL; P < 0.001). Visfatin was negatively associated with necro-inflammatory activity grade (r = −0.36; P = 0.007). The lowest levels were found in patients with the most advanced inflammation: grades 3–4 – 46.8 ± 17.1, grade 2 – 52.6 ± 18.4 and grade 1 – 75.2 ± 27.6 ng/mL; P = 0.017. A significant difference was also shown comparing patients with minimal inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver operating characteristic curve analysis for different necro-inflammatory activity – grade 1 vs grades 3–4 with area under the curve 0.81 indicated a good discriminant power for differentiation of moderate/severe inflammation, with the cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive value 0.90, negative predictive value 0.75). Serum visfatin concentration increases significantly in CHC patients. These findings suggest that visfatin is important in the pathogenesis of the inflammatory process in CHC. Visfatin may play a dual role as a pro-inflammatory or/and protective factor. The measurement of visfatin serum concentration may serve as an additional tool in distinguishing more advanced grades of the necro-inflammatory activity.