Among these studies, an increased IL-6 expression has been linked with HCC development.38, 43 Specifically, activation of IL-6 signaling through phosphorylation of STAT3 at Tyr705 and Ser727 has been detected in a wide variety of mouse and human liver cancer including IHCA.28, 43, 44, 45, 46 Especially in IHCA, dominant-active mutational changes in different proteins contributing to gp130-STAT3 activation are essential to lead toward benign tumor growth.43 However, the transition of IHCA into HCC and thus tumor initiation is not frequently found.47 This evidence concerns the gene IL6 and hepatocellular carcinoma.