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Background Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. Methods In this retrospective study, PCSK9 levels were evaluated by ELISA, in plasma samples from control (n = 24) and 178 patients diagnosed for HCC, cirrhosis, or chronic hepatitis, either positive or negative for HCV. Results HCV positive patients