Pemafibrate, a novel selective PPARα modulator, attenuates tamoxifen-induced fatty liver disease

Estrogen receptor (ER) antagonists, such as tamoxifen and toremifene, are widely used as adjuvant therapies for ER-positive breast cancer. These agents sometimes cause hepatosteatosis and steatohepatitis and it is problematic whether these agents should be withdrawn due to fatty liver disease and liver dysfunction. We herein describe a patient with fatty liver disease and hypertriglyceridemia during tamoxifen treatment, which significantly improved by adding pemafibrate, a novel PPARα activator designated as a selective PPARα modulator. Serial analysis during pemafibrate treatment revealed significant increases in circulating ketone bodies, which are indicators of hepatic fatty acid (FA) β-oxidation. As far as we know, this is the first report demonstrating the beneficial effect of pemafibrate on tamoxifen-induced fatty liver disease, which is likely due to enhanced hepatic FA β-oxidation by PPARα stimulation. Future large-scale studies will be needed to verify the current observation.