GENETIC ABNORMALITIES OF OXYGENSENSING PATHWAY, ERYTHROPOYETIN, AND JAK2 ARE NOT INVOLVED IN THE DEVELOPMENT OF POST-TRANSPLANT ERYTHROCYTOSIS OF PEDIATRIC LIVER RECIPIENTS

Objectives and Study: Ursodeoxycholate (UDCA) is used as treatment for cystic fibrosis liver disease (CFLD). It is hypothesized that the supposed therapeutic action of UDCA in CF conditions is either mediated via its choleretic activity or via effects on bile salt metabolism. In CF conditions, however, the effects of UDCA on biliary bile salt composition and on the enterohepatic circulation of bile salts have remained unclear. We evaluated, in Cftr knockout mice and wild type controls, the effects of UDCA treatment on the biliary bile salt composition and on the biosynthesis rate and pool size of cholate (CA), which is proportionally the major hydrophobic bile salt in mouse and man. Methods: Cftr-/-and control mice were either fed standard or treated with UDCA enriched chow (0.5% wt/wt) for 3 weeks. We characterized biliary bile salt composition after gallbladder cannulation and determined the CA synthesis rate and bile salt pool size using a microscale stable isotope dilution technique. Results: In non UDCA treated Cftr-/-mice the fractional biliary CA content was significantly higher compared to controls (61% vs. 46%, resp.; P