Although ~99% of circulating IGF-1 is bound to IGFBPs, predominantly to IGFBP-3, the most abundant IGFBP in human serum, case-control studies showed significantly lower IGF-1 and IGFBP-3 serum levels in the patients with ICC over the control group (Jozefiak et al., 2008; Serrano et al., 2006). This evidence concerns the gene IGF1 and intrahepatic cholangiocarcinoma.