Z Gastroenterol 2016; 54 - P48
DOI: 10.1055/s-0036-1584026

Gut permeability and neutrophil function in secondary sclerosing cholangitis of critically ill patients

M Tawdrous 1, A Horvath 1, B Schmerböck 2, B Leber 2, A Hartl 1, W Spindelböck 1, G Fauler 3, T Stojakovic 3, P Stiegler 2, V Stadlbauer 1
  • 1Medical University of Graz/Divison of Gastroenterology and Hepatology, Graz, Austria
  • 2Medical University of Graz/Divison of Transplantation Surgery, Graz, Austria
  • 3Medical University of Graz/Divison of Medical and Chemical Laboratory Diagnostics, Graz, Austria

Background: Secondary sclerosing cholangitis of critically ill patients (SSC-CIP) is a chronic progressive disease of the biliary tract. Consequences are cholestasis, infections and the development of biliary cirrhosis. The cause of SSC-CIP is unclear and a cure can only be achieved through liver transplantation. We hypothesize that altered gut permeability may be a reason for the development of SSC-CIP that induces an altered innate immune system.

Methods: Patients with SSC (n = 10) and healthy controls (n = 21) were investigated. Serum bile acids (assessed as unconjugated acids, taurine and glycine conjugates) were measured by a high resolution mass spectrometry. A ready-to-use ELISA was used to detect DAO in serum and Zonulin and Calprotectin in stool samples. Neutrophil function (oxidative burst and phagocytosis) was measured by flow cytometry.

Results: SSC patients show a significantly higher abundance of serum bile acids (unconjugated acids (p = 0.023), taurine (p < 0.001) and glycine conjugates (p = 0.023)) compared to controls. DAO (Median = 17.53 U/ml; p = 0.003), Zonulin (Median = 289.05 ng/ml; p = 0.048) and Calprotectin (Median = 80.13 µg/ml; p = 0.000) are also significantly higher in SSC patients than in healthy controls (9.36 U/ml; 66.43 ng/ml; 41.31 µg/ml respectively). SSC patients show a significantly higher percentage of primed neutrophils than healthy controls (p = 0.004).

Discussion: SSC-CIP patients have elevated serum bile acid levels as expected in cholestasis. Furthermore, our results indicate that SSC-CIP patients have altered gut permeability and increased neutrophil priming. However, it still remains unclear if this is a cause, a consequence, or a manifestation of the disease.