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  3. Medizin - Open Access LMU - Teil 20/22 Podcast
  4. Serum proteome profiling identifies novel and powerful markers of cystic fibrosis liver disease.
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.
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. 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. 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.

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