It is plausible that upregulation by either transposon or endogenous AKT, Notch and CAT oncogene in cholangiocytes or liver progenitor cells initiates biliary tumour formation or hepatocyte dedifferentiation following malignant transformation as recently described.34 Furthermore, we provide evidence that LTβR signalling is also important in maintaining endogenous Notch1-ICD/Hes1 in human liver cancer cell lines and correlates with Notch1 expression/signalling in patients with ICC. This evidence concerns the gene AKT1 and intrahepatic cholangiocarcinoma.