Z Gastroenterol 2012; 50 - P1_25
DOI: 10.1055/s-0031-1295755

Signature of three novel surrogate markers predicts liver stiffness and fibrosis stages in a cohort of patients with chronic liver disease

M Krawczyk 1, T Sauerbruch 2, A Höblinger 2, G Hess 3, F Lammert 4, F Grünhage 5
  • 1Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg
  • 2Medizinische Klinik und Poliklinik I, Innere Medizin, Bonn, Deutschland
  • 3Department of Internal Medicine, University Hospital Mainz, Mainz
  • 4Universitätsklinikum des Saarlandes, Homburg, Deutschland
  • 5Klinik für Innere Medizin II, Homburg

Aims: Latest experimental data suggests that placenta growth factor (PLGF), growth differentiation factor 15 (GDF15) and hepatic growth factor (HGF) are crucial for hepatic fibrogenesis (Hepatology 2011; PLoS One 2011). We now report a novel score of the top-predictive markers, including PLGF, GDF–15 and HGF, for the diagnosis of different degrees of liver stiffness in patients with chronic liver diseases.

Patients and Methods: Overall 834 patients were included. Transient elastography (TE) was employed to phenotype patients, who were subsequently subdivided in four different TE classes (0: ≤7.5kPa, 1: >7.5–9.5 kPa, 2: >9.5–12.5 kPa, 3: >12.5–17.5 kPa and 4: > 17.5 kPa). The AUC for the prediction of significant fibrosis (>7.5kPa) and the cut-off values for serum markers were determined. Odd ratios were calculated for the presence of significantly increased TE values or for histological stage of fibrosis.

Results: Patients with TE class 0/1 (68%) were overrepresented in our cohort (median age 51 years, 61% males). Cut-off levels for the three markers to differentiate between TE <7.5 and ≥7.5kPa were PLGF=19 pg/ml, GDF15=730pg/ml, and HGF=15pg/ml. Overall, 28.3% patients displayed no, 23.1% one, 21.2% two and 27.3% three markers above the defined cut-offs. Of note, the presence of any marker above the cut-off was associated with OR=5.4 (95% CI 3.7–7.8, p<0.001) to present with TE >7.5 and with OR=18.6 (95% CI 8.1–42.7, p<0.001) to present with TE >12.5 kPa. The score was also associated with histological fibrosis stages F>1 vs. F0/1 (OR=5.3, 95% CI 2.3–11.0, p<0.001) and bridging fibrosis/cirrhosis (i.e. F3/F4 vs. F0/F1/F2, OR=7.2, 95% CI 3.3–15.9, p<0.001).

Discussion: The combination of serum PLGF, GDF15 and HGF levels accurately predicts the presence of significant liver fibrosis as detected by TE or histology. Further prospective evaluation of this novel fibrosis signature is needed to define their value for clinical practice.