Journalartikel

Jahr der Veröffentlichung: 2013

Zeitschrift: PLoS ONE

Bandnummer: 8

Heftnummer: 3

ISSN: 1932-6203

Open Access Status: Gold

DOI Link: https://doi.org/10.1371/journal.pone.0058955

Verlag: Public Library of Science

Abstract: 

Background and Aims: Cystic Fibrosis associated liver disease (CFLD) develops in approximately 30% of CF patients. However, routine sensitive diagnostic tools for CFLD are lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CFLD.

Methods: 45 CF patients were included in the study and received transient elastography. Differential regulation of 220 different serum proteins was assessed in a subgroup of patients with and without CFLD. Most interesting candidate proteins were further quantified and validated by ELISA in the whole patient cohort. To assess a potential relation of biomarker expression to the degree of hepatic fibrosis, serum biomarkers were further determined in 18 HCV patients where liver histology was available.

Results: 43 serum proteins differed at least 2-fold in patients with CFLD compared to those without liver disease as identified in proteome profiling. In ELISA quantifications, TIMP-4 and Endoglin were significantly up-regulated in patients with CFLD as diagnosed by clinical guidelines or increased liver stiffness. Pentraxin-3 was significantly decreased in patients with CFLD. Serum TIMP-4 and Endoglin showed highest values in HCV patients with liver cirrhosis compared to those with fibrosis but without cirrhosis. At a cut-off value of 6.3 kPa, transient elastography compassed a very high diagnostic accuracy and specificity for the detection of CFLD. Among the biomarkers, TIMP-4 and Endoglin exhibited a high diagnostic accuracy for CFLD. Diagnostic sensitivities and negative predictive values were increased when elastography and TIMP-4 and Endoglin were combined for the detection of CFLD.

Conclusions: Serum TIMP-4 and Endoglin are increased in CFLD and their expression correlates with hepatic staging. Determination of TIMP-4 and Endoglin together with transient elastography can increase the sensitivity for the non-invasive diagnosis of CFLD.

Harvard-Zitierstil: Rath, T., Hage, L., Kuegler, M., Menendez, K., Zachoval, R., Naehrlich, L., et al. (2013) Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease, PLoS ONE, 8(3), Article e58955. https://doi.org/10.1371/journal.pone.0058955

APA-Zitierstil: Rath, T., Hage, L., Kuegler, M., Menendez, K., Zachoval, R., Naehrlich, L., Schulz, R., Roderfeld, M., & Roeb, E. (2013). Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease. PLoS ONE. 8(3), Article e58955. https://doi.org/10.1371/journal.pone.0058955