The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively.
Progressive familial intrahepatic cholestasis (PFIC or Byler disease) is a rare autosomal recessive form of severe and fatal cholestatic liver disease.
Because expression of the familial intrahepatic cholestasis 1 gene occurs in several organs, including the small intestine, pancreas, and liver, and it is involved in enterohepatic bile acid circulation, post-LT steatosis may be due to a malfunction of the ATP8B1 product.
We searched for FIC1 mutations and analyzed the outcome of extrahepatic features after liver transplantation in two children with this form of progressive familial intrahepatic cholestasis associated with chronic unexplained diarrhea and short stature.
Thus far, five representatives of PFIC (named PFIC1-5) caused by pathogenic mutations present in both alleles of <i>ATP8B1</i>, <i>ABCB11</i>, <i>ABCB4</i>, <i>TJP2,</i> and <i>NR1H4</i> have been described.