Expanding etiology of progressive familial intrahepatic cholestasis

Table 1 Medical management of pruritus in children

Medicine	Dose	Mechanism of action
Cholestyramine	Initial dose: 2 g BID	Ion exchange resin which acts as BA binder in the intestine
	(max dose 24 g/d)	Decreased ileal BA absorption, Increased BA excretion (in feces)
Naltrexone	Initial dose: 0.25-5 mg/kg per day	Opioid antagonist
	(max dose 50 mg/d)	Block the permissive activity on pruritus neuronal signaling
Rifampicin	Initial dose: 5 mg/kg	PXR agonist
		Induces CYP3A4
	(max dose 20 mg/kg per day)	Increases metabolism and renal excretion of pruritogenic substances
		Antibacterial effect may modify intestinal metabolism of pruritogenic substances
Sertraline	Initial dose: 1 mg/kg per day	Serotonin reuptake inhibitor
	(max dose: 4 mg/kg per day)	Proposed mechanism includes increase in central serotonergic tone, which regulates pruritus
Ursodeoxycholic acid	600 mg/m2 per day	Tertiary BA
		Increases bile secretion
		Reduces ileal absorption of hydrophilic BAs

BA: Bile acid; PXR: Pregnane X receptor.

Table 2 Adult manifestations of progressive familial intrahepatic cholestasis gene mutations

Etiology	Genetic defect	Manifestations
FIC1 deficiency	ATP8B1	BRIC1
		ICP1 and contraceptive-induced cholestasis
		Cryptogenic cirrhosis
BSEP deficiency	ABCB11	BRIC2
		ICP2 and contraceptive-induced cholestasis
		DILI
		Cryptogenic cirrhosis
MDR3 deficiency	ABCB4	ICP3 and contraceptive-induced cholestasis
		Drug induced cholestasis
		Low phospholipid-associated cholestasis
		Cholesterol gallstone disease
		Biliary fibrosis or liver cirrhosis without cholestasis
		Cryptogenic cirrhosis
TJP2 deficiency	TJP2	Cryptogenic cirrhosis
FXR	NR1H4	ICP
		Drug induced cholestasis associated with propylthiouracil

BRIC: Benign recurrent intrahepatic cholestasis; BSEP: Bile salt export pump; ICP: Intrahepatic cholestasis of pregnancy; DILI: Drug induce liver injury.