FGF21 and fatty liver disease: In patients with IF and PN dependence, and in PNAC animal models, cholestasis is associated with the downregulation of canalicular bile acid and phytosterols export transporters, upregulation of the sinusoidal bile acid uptake transporter, and insufficient suppression of bile acid synthesis genes, whereas hepatic steatosis is associated with intestinal microbial dysbiosis, reactive oxygen species (ROS) accumulation, apoptosis, and increased FGF21 (Fig. 4).