*7.2. Ursodeoxycholic Acid (UDCA)*

UDCA is one of the most commonly used agents for the treatment of cholestatic disorders. It showed promising results in animal models and in patients by alleviating disease symptoms. Although the exact mechanism of action of UDCA is not known, it was reported that the compound may act by correcting a potential trafficking deficiency of BSEP mutants, as well as by reducing the internalization of the transporter [112,129,130]. Furthermore, UDCA also reduces the overall hydrophobicity of the bile acid pool, thereby protecting hepatocytes from damage [131]. However, in some patients UDCA failed alleviate disease symptoms. Likely this finding reflects the genetic diversity of the underlying disease [129].

A UDCA derivative, norUDCA, is also being used for treatment of BSEP-related diseases. Because of its capacity for cholehepatic shunting (i.e., bypassing the normal enterohepatic circulation), norUDCA counteracts bile duct damage via bicarbonate-rich choleresis. Furthermore, norUDCA has antifibrotic, antiproliferative and anti-inflammatory properties and propagates bile acid detoxification through elimination via the urine [131–133].
