Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis

摘要: Background & Aims: Progressive familiar intrahepatic cholestasis (PFIC), an inherited liver disease of childhood, is characterized by and either normal or increased serum gamma-glutamyltransferase activity. Patients with activity have mutations the FIC1 locus on chromosome 18q21 BSEP gene 2q24, Also, patients bile acid synthesis defects low We investigated expression salt export pump (BSEP) in samples from a PFIC phenotype correlated this mutations, Methods: multidrug resistance protein 2 (MRP2) expressions were studied immunohistochemistry specimens 28 mutation analysis 19 patients. Bile kinetics 1 patient. Results: Sixteen showed no canalicular staining. Staining for MRP2 pattern all but these samples. Ten mutations; was lacking 10 patients, No found 9 except 1, normal. concentration BSEP-negative/MRP2-positive 0.2 +/- mmol/L (n = 9; <1% normal) BSEP-positive 18.1 9.9 3; 40% normal). The kinetic study confirmed dramatic decrease secretion BSEP-negative Conclusions: findings show close correlation between expression. Biliary salts greatly reduced