Progressive familial intrahepatic cholestasis: diagnosis, management, and treatment

Figures & data

Table 1 Genetic features of PFIC subtypes

Disease	Byler disease (PFIC 1)	SPGP/BSEP deficiency (PFIC 2)	MDR3 deficiency (PFIC 3)
Chromosome	18q21-q22	2q24	7q21
Gene	FIC 1 (ATP8B1)	BSEP (ABCB11)	PGY3 (ABCB4, MDR 3)
Gene function	FIC1 translocates phospholipids from outer to inner canalicular membrane	Bile salt export pump	Phosphatidylcholine transport into bile

Abbreviations: ABCB11, ATP Binding Cassette Subfamily B Member 11; ABCB4 (PGY3), ATP binding cassette subfamily B member 4; BSEP, bile salt export pump; FIC1, familial intrahepatic cholestasis; MDR3, multidrug resistance Class III; PFIC, progressive familial intrahepatic cholestasis.

Table 2 Laboratory findings in PFIC subtypes. (N= normal, H= high/elevated, L= low/depleted)

	PFIC type 1	PFIC type 2	PFIC type 3
Serum GGT	N	N	H
Serum direct bilirubin	H	H	H
Serum bile acids	H(++)	H(+++)	H(+)
Serum ALP	H	H	H
Serum ALT	H	H	H
Biliary phospholipids	N	N	L
Serum5′-nucleotidase	H	H	H
Serum AFP	N	H	N

Abbreviations: PFIC, progressive familial intrahepatic cholestasis; AFP, alphafetoprotein; ALP, alkaline phosphatase; ALT, alanine aminotransferase; GGT, gamma glutamyl transferase.

Table 3 Clinical features of PFIC subtypes

	PFIC type 1	PFIC type 2	PFIC type 3
Age of onset	Early infancy	Early infancy	Later in childhood or young adulthood
Extrahepaticmanifestations	Watery diarrhea Pancreatitis Sensorineural hearing loss	Uncommon	None
Pruritus	Severe	Very severe	Moderate
Cholesterol stone formation	Absent	Increased	Increased
Progression of PFIC subtypes	Liver cirrhosis and rapid progression to ESLD Patients do not have increased risk for development of liver tumors.	Progression even more quickly to end-stage liver disease, require liver transplantation during the first decade of life. Risk of development of liver tumors are high.	Insidious Risk of development of liver tumors are mildly increased.

Abbreviations: ESLD, end-stage liver disease; PFIC, progressive familial intrahepatic cholestasis.

Table 4 Liver biopsy, electron microscopy features and treatment modalities for PFIC subtypes

	PFIC type 1	PFIC type 2	PFIC type 3
Histology	Intracanalicular cholestasis, bile duct proliferation at the late phase	Bile duct proliferation at the late phase, lobular and portal fibrosis	Extensive bile duct proliferation and periportal fibrosis
Bile on electronmicroscopy	Granular called “Byler bile”	Amorphous or filamentous	_
Therapy	UDCA biliary diversion liver transplantation	UDCA biliary diversion liver transplantation	UDCA liver transplantation

Abbreviations: PFIC, progressive familial intrahepatic cholestasis; UDCA, ursodeoxycholic acid.

Figure 1 An infant with PFIC, jaundice and scratching marks.