Primary sclerosing cholangitis: Updates in diagnosis and therapy

Table 1 Diseases most commonly associated with PSC.

Celiac disease

Rheumatoid arthritis

Thyroiditis

Sjogren’s syndrome

Lupus erythematosus

Lupic nephritis

Chronic pancreatitis

Retroperitoneal fibrosis

Systemic sclerosis

Peyronie’s disease

Autoimmune hemolytic anemia

Immune thrombocytopenic purpura

Membranous nephropathy

Histiocytosis X

Cystic fibrosis

Angioblastic lymphadenopathy

Intra-abdominal adenopathy

Vasculitis

Pseudotumor of the orbit

Gallbladder disease

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.

Table 3 Regimens and effects of UDCA for PSC therapy.

Regimen		Assessment	Outcome	References
Low doses (single administration)	8-13 mg/(kg·d)	Liver biochemistry	Improved	[92]
		Histology, symptoms, survival	Ineffective
	13-15 mg/(kg·d)	Liver biochemistry	Improved	[90]
		Histology, symptoms, survival	Ineffective
Low doses (multiple administration)1	10-12 mg/(kg·d) t.i.d.	Liver biochemistry	Improved	[93]
		Histology, symptoms	No progression
	20 mg/(kg·d)	Liver biochemistry	Improved	[94]
		Histology	Improved
High doses	25-30 mg/(kg·d)	ERCP	No progression
		Liver biochemistry	Improved
		Mayo risk score and survival at 4 yr	Improved	[95]
Combination	UDCA 650 mg/d + azathioprine 1-1.5 mg/(kg·d)+ prednisolone 1-10 mg/(kg·d)	Liver biochemistry	Improved
		Histology	Improved	[96]
		ERCP	Improved

¹Comparable effects for multiple vs single administration.