Z Gastroenterol 2012; 50 - K070
DOI: 10.1055/s-0032-1324005

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

M Krawczyk 1, A Höblinger 2, G Hess 3, T Sauerbruch 2, F Lammert 1, F Grünhage 1
  • 1Saarland University Medical Center, Medical Department II, Homburg, Germany
  • 2University Hospital Bonn, Department of Internal Medicine I, Bonn, Germany
  • 3University of Mainz, Department of Internal Medicine, Mainz, Germany

Background and aims: Recent experimental data suggest that placenta growth factor (PLGF), growth differentiation factor 15 (GDF15) and hepatic growth factor (HGF) are critical for hepatic fibrogenesis (Hepatology 2011; PLoS One 2011). Our previously reported panel of novel serum fibrosis markers underlines the importance of these markers for humans (Grünhage et al. ASSLD 2010). We now report a novel score of top-predictive markers including PLGF, GDF-15 and HGF for the diagnosis of different degrees of liver stiffness and histological fibrosis stages in a cohort of patients with chronic liver disease.

Methods: Overall, 834 CLD patients were recruited (median age 51 years, range 18–84 years, 61% males). Liver fibrosis was phenotyped using transient elastography (TE). Serum levels of PLGF, GDF15 and HGF were measured in 824 patients. The AUC for the prediction of significant fibrosis (>7.5 kPa) and the cut-off values for serum markers were determined. The tested scores included 0, 1 or 2 markers above the predicted cut-off. Odd ratios were calculated for the presence of significantly increased TE values (>7.5 or >17.5kPa, respectively) or the presence of histological fibrosis using chi-square tests.

Results: Cut-off levels for the three markers to differentiate between TE <7.5 and ≥7.5kPa were PLGF=19 pg/ml, GDF15=730 pg/ml, and HGF=15 pg/ml. Overall, 28.3% patients displayed no, 23.1% one, 21.2% two and 27.3% three markers above the defined cut-offs. The presence of any marker above the cut-off was associated with an OR of 5.4 (95% CI 3.7–7.8, p<0.001) to present with TE >7.5 kPa and with an OR of 18.6 (95% CI 8.1–42.7, p<0.001) to present with TE >17.5 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-F2, OR=7.2, 95% CI 3.3–15.9, p<0.001).

Conclusion: The combination of serum PLGF, GDF15 and HGF levels accurately predicts the presence of significant liver fibrosis as detected by TE or histology.