In the present study, we analyzed core and NS5B polymorphisms/mutations which have been associated with non-responsiveness or a better response to IFN/RBV combination therapy, and/or resistance to polymerase inhibitor drugs, HCC, liver steatosis and IR, in chronically infected drug-naïve patients from Venezuela, and these polymorphisms/mutations were compared with worldwide HCV isolates. This evidence concerns the gene IFNA1 and hepatocellular carcinoma.