Primary sclerosing cholangitis: Updates in diagnosis and therapy

Table 2 Targets, mechanisms and effects of UDCA therapy.

Target	Mechanisms	Effects	References
Cholesterol	Intestinal absorption ↓	Biliary cholesterol decreased by 40-60%	[118]
	Conversion to bile acids ↑	Serum LDL and HDL cholesterol decreased
Bile acid pool	Ileal absorption of endogenous hydrophobic bile acids ↓	Serum UDCA increased by 10-64%
		Total bile acids ↑ Hydrophobic bile acids ↓	[74-77,119,120]
		Unchanged hydrophilic bile acid pool	[121,122]
Bile flow	Exocytocis and canalicular transport ↑(due to ↑ cytoplasmatic free Ca2+)
	Modulation of membrane transport proteins	Excretory rates and bile acids transit time ↑	[123-125]
	Hypercholeresis		[80]
Gallbladder	Modulation of smooth muscle contractility (CCK receptor + cholinergic nerves)	Fasting gallbladder volume↑	[126-128]
		Postprandial gallbladder emptying ν
Gallbladder bile	Biliary total proteins ↓	Crystallization-promoting activity ↓	[129,130]
	Concanavalin A-binding fraction ↓	Inhibition of cholesterol crystallization
Immune system	Expression of MHC class I and II ↓	Immunomodulatory effect T-cell hepatocellular damage ↓	[82,83]
Cells	Hydrophobic bile acid induced cell damage↓	Cytoprotection (e.g., liver damage ↓)	[85,86]
	Apoptosis or necrosis ↓
Neoplasms	Unknown (decreased fecal hydrophobic deoxycholate, lithocholate)	Chemo protection (neoplasm proliferation ↓)	[87,89,131]

↓, decreased; ↑, increased; ν, unchanged; MHC, major histocompatibility complex.