Z Gastroenterol 2015; 53 - A3_11
DOI: 10.1055/s-0035-1568031

Delayed intrahepatic cholestasis induced by anabolic steroids in a patient with haploinsufficiency of the pregnane X receptor (PXR/NR1I2)

R Liebe 1, M Krawczyk 1, J Raszeja-Wyszomirska 3, B Kruk 2, R Preis 4, J Trottier 5, O Barbier 5, P Milkiewicz 6, F Lammert 1
  • 1Saarland University, Department of Medicine II, Homburg, Germany
  • 2Medical University of Warsaw, Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Warsaw, Poland
  • 3Medical University of Warsaw, Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Warsaw, Poland
  • 4Gemeinschaftspraxis für Humangenetik, DNA Diagnostik Labor, Homburg, Germany
  • 5Laval University, Research Center and the Faculty of Pharmacy, Québec, Canada
  • 6Pomeranian Medical University, Department of Clinical and Molecular Biochemistry, Szczecin, Poland

Case description: We describe a 32 year old male patient who developed cholestatic liver injury two weeks after a 2-month course of anabolic steroids.

Methods and results: Next generation sequencing of a panel of 24 cholestasis-related genes revealed a heterozygous 2 basepair deletion in exon 1 of the pregnane X receptor (PCR/NR1I2) gene. Analysis of serum bile salts revealed marked imbalances, strongly resembling the changes observed in patients with biliary obstruction (BO). PXR haploinsufficiency coupled to AAS severely reduced the secretion of bile, causing massive accumulation of taurine- and glycine-conjugated primary bile acids. Absence of secondary BAs such as DCA and LCA in his plasma is consistent with an impaired biliary secretion. LCA was absent from the PXR sample, its 3-glucuronide derivative presented an impressive 112-fold accumulation; while the same accumulation was limited to 7.7-fold in BO samples.

Conclusions: PXR haploinsufficiency reveals a network of transcriptional regulatory functions activated in the liver under xenobiotic stress, which appears to require two functional copies of the gene. Deranged bile salt levels following anabolic steroid consumption outline the central role of PXR in bile acid synthesis, modification and export. Comparison of BA levels found in the serum of the PXR/NR1I2 haploinsufficient individual with patients suffering from biliary obstruction of other sources indicate subtle but significant differences in glucuronidation.

These findings suggest a more central and crucial role of PXR/NR1I2 in the hepatic handling and clearance of bile acids than has been previously suggested.

Corresponding author: Liebe, Roman

E-Mail: Roman.Liebe@uniklinikum-saarland.de