Second, the identification of the mechanisms underlying replication enhancing mutations in NS5A (prototype: S2204I/R, referring to the amino acid position in the polyprotein of Con1) and NS5B (R2884G) [17], allowed the development of an inhibitor regimen termed PCi, based on the combined chemical inhibition of Phosphatidylinositol-4 kinase III alpha (PI4KA) and Casein Kinase Ia (CKIα), enabling RNA replication of gt1b isolates by compensating for the overexpression of PI4KA in HCC-derived cells, compared to human hepatocytes [18]. This evidence concerns the gene CSNK1A1 and hepatocellular carcinoma.