Differences in presentation and progression between severe FIC1 and BSEP deficiencies

Ludmila Pawlikowska, Sandra Strautnieks, Irena Jankowska, Piotr Czubkowski, Karan Emerick, Anthony Antoniou, Catherine Wanty, Bjorn Fischler, Emmanuel Jacquemin, Sami Wali, Samra Blanchard, Inge Merete Nielsen, Billy Bourke, Shirley McQuaid, Florence Lacaille, Jane A. Byrne, Albertien M. van Eerde, Kaija Leena Kolho, Leo Klomp, Roderick HouwenPeter Bacchetti, Steven Lobritto, Vera Hupertz, Patricia McClean, Giorgina Mieli-Vergani, Benjamin Shneider, Antal Nemeth, Etienne Sokal, Nelson B. Freimer, A. S. Knisely, Philip Rosenthal, Peter F. Whitington, Joanna Pawlowska, Richard J. Thompson, Laura N. Bull*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

156 Scopus citations


Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. Methods: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. Results: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. Conclusions: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.

Original languageEnglish (US)
Pages (from-to)170-178
Number of pages9
JournalJournal of Hepatology
Issue number1
StatePublished - Jul 2010


  • ABCB11
  • ATP binding cassette protein
  • ATP8B1
  • BSEP
  • Cholestasis
  • FIC1
  • Genetics
  • P-type ATPase
  • Pediatrics
  • Transport protein

ASJC Scopus subject areas

  • Hepatology


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