Bezafibrate exerts multiple effects on lipid metabolism by activating the peroxisome proliferator-activated receptor-α, which modulates the expression of key genes of lipid transport, lipoprotein metabolism as well as inflammation. The aim of the present study was to assess the efficacy and safety of bezafibrate in patients with advanced chronic hepatitis C. A total of 34 patients received oral bezafibrate treatment (400 mg/day) on the basis of a prospective observational open-label study design. Clinical, biochemical and virological data were evaluated during a mean treatment duration of 19 months. In a subpopulation (n=8), cytokine expression analysis was carried out and compared with an hepatitis C virus treatment-naive control group (n=7). A significant improvement in aspartate aminotransferase (P=0.007), alanine aminotransferase (P<0.0001), alkaline phosphatase (P=0.001), γ-glutamyltranspeptidase levels (P=0.001) and aspartate aminotransferase-to-platelets ratio index Score (P=0.026) could be found at the end of observation. No significant effect on viral load was observed. Bezafibrate treatment for at least 4 months markedly increased interferon-γ expression compared with the treatment-naive patients (4.81 vs. 1.63 arbitrary units; P=0.005), whereas tumour necrosis factor-α and interleukin-6 levels were not significantly influenced. This observational study provides evidence that bezafibrate is effective for patients with advanced chronic hepatitis C by reducing liver enzymes significantly and should be further evaluated as a potentially beneficial maintenance therapy.