The metabolic impact of IDH1/2 mutations as well as IDH3A down-regulation in HCC could be linked to a reduced NADPH production, which results insufficient to maintain a favorable GSH:GSSG ratio thus increasing steady-state ROS and in turn oxidation of cellular components and DNA mutation rate, as already reported for others cancers involving IDH1/2 mutations [80,81]. Here, IDH1 is linked to hepatocellular carcinoma.