RB1 and hepatocellular carcinoma: It is proposed that when HBx expression is high in infected liver, it down-regulates the expression of cyclin dependent kinase (CDK) inhibitors and the retinoblastoma gene product, Rb [66], as well as stimulates β-catenin activity [67], but when HBx expression is low or absent, as in HCC nodules, these proteins are often mutated [68] to yield the same functional consequences as their wild type counterparts in HBx expressing cells.