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Hepatology. 2016 Sep;64(3):843-52. doi: 10.1002/hep.28543. Epub 2016 Apr 20.

CD14 is associated with biliary stricture formation.

Hepatology (Baltimore, Md.)

Kilian Friedrich, Mark Smit, Maik Brune, Thomas Giese, Christian Rupp, Andreas Wannhoff, Petra Kloeters, Yvonne Leopold, Gerald Ulrich Denk, Karl Heinz Weiss, Wolfgang Stremmel, Peter Sauer, Simon Hohenester, Peter Schirmacher, Peter Schemmer, Daniel Nils Gotthardt


  1. Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.
  2. Department of Internal Medicine I, University Hospital of Heidelberg, Heidelberg, Germany.
  3. Heidelberg University Hospital, Institute for Immunology, Heidelberg, Germany.
  4. Liver Center Munich, Department of Medicine II, University of Munich (LMU), Munich, Germany.
  5. Transplantation Center, University of Munich, Munich, Germany.
  6. Heidelberg University Hospital, Institute for Pathology, Heidelberg, Germany.
  7. Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 26970220 DOI: 10.1002/hep.28543


UNLABELLED: The pathogenesis of intrahepatic biliary stricture formation in patients with primary sclerosing cholangitis (PSC) or after liver transplantation (LTx) remains elusive. CD14 receptor signaling is a key mediator of the innate immune system; its common genetic variant is associated with alcoholic liver disease. PSC and LTx cohort patients and primary biliary cirrhosis (PBC) control patients were genotyped for the CD14 -260C>T (rs2569190) polymorphism, and genotypes were correlated with long-term clinical outcome. Biliary tissue, bile, and whole blood of PSC patients and healthy controls were screened for markers of the innate immune system and bacterial infection. In 121 PSC patients, the CD14 -260C>T genotype was associated with development of dominant bile duct strictures (P = 0.02). In 365 LTx patients, TT carriers (4.1%) were protected against the formation of nonanastomotic biliary strictures versus CC/CT patients (12.6%; P = 0.01). Chemokine ligand 8 (P = 0.04) and chemokine receptor 6 (P = 0.004) were up-regulated in biliary tissue of PSC patients with the TT versus the CC/CT genotype. Lipopolysaccharide whole-blood stimulation resulted in a significant change in interleukin (IL)-8 (P = 0.05) and IL-12p40 levels (P = 0.04) in healthy control subjects carrying the TT genotype. TT PSC patients were protected against Gram-negative bacterial biliary infection (TT: 0% vs.

CC/CT: 22.5%; P = 0.02). Serum-soluble CD14 levels correlated with the CD14 -260C>T genotype (P = 0.02), representing an independent risk indicator of survival in PSC patients (hazard ratio, 0.40; 95% confidence interval, 0.19-0.86; P =0.01).

CONCLUSIONS: The function of the innate immune response by CD14 is crucial during biliary infection and stricture formation. The benefits of CD14 signaling modification should be addressed in future studies. (Hepatology 2016;64:843-852).

© 2016 by the American Association for the Study of Liver Diseases.


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