Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website


Volume 7, Number 2, April 2014, pages 39-43

A Comprehensive Review of Progressive Familial Intrahepatic Cholestasis (PFIC): Genetic Disorders of Hepatocanalicular Transporters


Table 1. Characteristic Features of the Three Types of Progressive Familial Intrahepatic Cholestasis
BSEP: bile salt export protein; MDR3: multidrug resistance protein; GGTL: gamma glutamyl transpeptidase; ALT: alkaline tranferase; AFP: alpha fetoprotein.
InheritanceAutosomal recessiveAutosomal recessiveAutosomal recessive
Age of onsetNeonatesNeonates1 month - 20 years
Function of hereditary defectAminophospholipid translocaseBile acid secretionPhosphatidylcholine secretion
Serum GGTNormalNormalHigh
Serum ALTMildly elevated> 5 × normal> 5 × normal
Serum AFPNormalelevatedNormal
Serum primary bile acid (PBA) concentrationVery highVery highHigh
Lipoprotein XPresentPresentAbsent
AlbuminLowUsually normalNormal
Hepatocyte locationCanalicular membraneCanalicular membraneCanalicular membrane
Other sites of expressionCholangiocytesPancreasIntestinesNoneNone
Functional defectATP dependent aminophospholipid transportATP dependent bile acid transport in bileATP dependent phosphatidylcholine translocation in bile
Liver biopsy
HistologyMinimal giant cell transformation, intracanalicular cholestasis, no ductal proliferation, minimal inflammation Late fibrosisGiant cell transformation, intracanalicular cholestasis, no ductular proliferation, moderate inflammation, fibrosisGiant cell transformation, intracanalicular cholestatis, ductular proliferation, moderate inflammation, marked fibrosis
Electron microscopyCoarsely granular bile Loss of microvilli, swollen microvilliAmorphous filamentous bile Loss of microvilliPresence of cholesterol crystals Loss of microvilli
ImmunohistochemistryBSEP positiveBSEP negativeBSEP positive
MDR3 positiveMDR3 positiveMDR3 negative
GGT negativeGGT negative to weakly positiveGGT positive


Table 2. Differential Diagnosis of PFIC
A) Disorders of bile acid synthesis biosynthesis and conjugation
  i) 3-oxo-4-steroid 5-reductase deficiency
  ii) 3 -hydroxy-5-C27-steroid dehydrogenase/isomerase deficiency
  iii) Oxysterol 7-hydroxylase deficiency
  iv) Bile acid-CoA: amino-acid N-acyltransferase deficiency (familial hypercholanemia)
B) Disorders of embryogenesis
  i) Alagille syndrome (jagged 1 defect, syndromic bile duct paucity)
  ii) Ductal plate malformation (autosomal recessive polycystic kidney disease, autosomal dominant polycystic liver disease, Caroli’s disease)
C) Trafficking and canalicular targeting defects
  i) Arthrogryposis, renal dysfunction, cholestasis
D) Tight, junction defects
  i) Neonatal ichthyosis sclerosing cholangitis
  ii) Familial Amish hypercholanemia
E) Miscellaneous
  i) Aagenaes syndrome ( hereditary cholestasis with lymphedema)
  ii) North American Indian Childhood Cirrhosis