Topic: Bates and cholestasis Cholestasis includes primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), which develops as a result of damage or destruction of bile ducts, leading to intracellular retention of toxic bile components, including bile salts. Cholestasis can lead to liver fibrosis and cirrhosis if left untreated. The only effective drug option available is ursodeoxycholic acid (UDCA), which can slow the progression of PBC, especially in patients with stage I-II disease. However, some patients respond poorly to ursodeoxycholic acid, and some may even be non-responders. In patients with PSC, UDCA treatment does not improve their survival and its recommended use remains controversial. This dictates the need to seek other effective treatments. Hepatic transport proteins located in the basolateral (hepatic sinusoidal) and apical (tubular) membranes of hepatocytes determine the formation and secretion of bile, and nuclear receptors (NRs) are involved in the management of these hepatic transport proteins and are therefore therapeutic targets in cholestatic liver disease. One of these NRs is peroxisome proliferator-activated receptor alpha (PPARα), which plays a central role in maintaining the stability of the body’s internal environment of cholesterol, lipids, and bile acids through the expression of genes that regulate bile synthesis and transport, including cytochrome P450 (CYP) isoform 7A1 (CYP7A1), CYP27A1 CYP8B1, guanosine 5′-diphosphate-glucuronosyltransferase 1A1, 1A3, 1A4, 1A6, hydroxysteroid sulfotransferase 2A1, multidrug resistance protein 3 (MDR3), and apical hepatic sinusoidal bile acid transporter. Although the expression of these genes can modify cholestatic liver disease, only a few genes have been extensively studied and the mechanism of action of PPARα is not clear. This study summarized the current literature on the efficacy of PPARα agonists in the treatment of chronic cholestatic liver disease and found that fenofibrate could improve cholestatic liver disease through the transcriptional activity of MDR3 in addition to the reported effective effect of PPARα activation in the liver, which could lead to the use of PPARα agonists (e.g. fenofibrate) in the treatment of cholestatic liver disease in adults, especially for This finding provides strong evidence for the application of PPARα agonists (such as fenofibrate) for the treatment of cholestatic liver disease in adults, especially in patients who do not respond adequately to UDCA treatment.