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PLoS One. 2017 Mar 16;12(3):e0173506. doi: 10.1371/journal.pone.0173506. eCollection 2017.

Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease.

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Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Laboratory of Metabolic Liver Diseases, Department of General, Transplantation and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
Roche Diagnostics, Grenzach-Wyhlen, Germany.
Department of Medicine III, Westpfalz-Klinikum, Kaiserslautern, Germany.
Department of Gastroenterology and Oncology, RKN-Hospital, Grevenbroich, Germany.


Latest data suggest that placental growth factor (PLGF), growth differentiation factor-15 (GDF-15) and hepatic growth factor (HGF) are involved in hepatic fibrogenesis. Diagnostic performance of these markers for non-invasive liver fibrosis prediction was evaluated based on liver histology and stiffness. In total 834 patients were recruited. Receiver-operating-characteristics were used to define cut-offs for markers correlating to fibrosis stages. Odds-ratios were calculated for the presence/absence of fibrosis/cirrhosis and confirmed in the sub-group of patients phenotyped by elastography only. Logistic and uni- and multivariate regression analyses were used to test for association of markers with liver fibrosis stages and for independent prediction of liver histology and stiffness. Marker concentrations correlated significantly (P<0.001) with histology and stiffness. Cut-offs for liver fibrosis (≥F2) were PLGF = 20.20 pg/ml, GDF15 = 1582.76 pg/ml and HGF = 2598.00 pg/ml. Logistic regression confirmed an increase of ORs from 3.6 over 33.0 to 108.4 with incremental (1-3) markers positive for increased liver stiffness (≥12.8kPa; all P<0.05). Subgroup analysis revealed associations with advanced fibrosis for HCV (three markers positive: OR = 59.9, CI 23.4-153.4, P<0.001) and non-HCV patients (three markers positive: OR = 144, CI 59-3383, P<0.001). Overall, serum markers identified additional 50% of patients at risk for advanced fibrosis presenting with low elastography results. In conclusion, this novel combination of markers reflects the presence of significant liver fibrosis detected by elastography and histology and may also identify patients at risk presenting with low elastography values.

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