GDF ‐15 Levels in Cirrhosis Are Linked to Hepatic Fibrogenesis, Bacterial Translocation, and Worse Clinical Outcomes

作者：Benedikt Hofer, T. Perkmann, Ksenia Brusilovskaya, Lorenz Balcar, Marlene Hintersteininger, Georg Kramer, Benedikt Simbrunner, Esther Caparros, Rubén Francés, B. Eichelberger, Silvia Lee, Kerstin Zinober, Benjamin Bödendorfer, Borka Radovanovic‐Petrova, Paul Thöne, Christian Sebesta, Mathias Jachs, L Hartl, Philipp Schwabl, Mattias Mandorfer, Simon Panzer, Thomas Reiberger, Thomas Gremmel · 发表于：Liver International · 年份：2026 · DOI：10.1111/liv.70516 · 被引用次数：3 · 研究领域：GDF15 and Related Biomarkers、IL-33, ST2, and ILC Pathways、Connective Tissue Growth Factor Research

BACKGROUND &AIMS: Growth differentiation factor-15 (GDF-15), a cell stress-induced cytokine, is implicated in liver disease pathophysiology. We investigated GDF-15 in cirrhosis, focusing on its association with disease-driving pathomechanisms, platelet function, hepatic decompensation, and mortality. METHODS: We included patients with cirrhosis undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital. Platelet surface P-selectin and glycoprotein IIb/IIIa (GPIIb/IIIa) expression after agonist stimulation were assessed by flow cytometry as platelet activation markers. GDF-15 serum levels were quantified by electrochemiluminescence immunoassay. RESULTS: Among 106 patients (median age 55.1 years; 70.8% male), median GDF-15 was 2880 (1850-4770) pg/mL. GDF-15 correlated with hepatic dysfunction (MELD Spearman's ρ: 0.50; albumin ρ: -0.57), HVPG (ρ: 0.47), systemic inflammation (C-reactive protein ρ: 0.45; interleukin 6 [IL-6] ρ: 0.55; procalcitonin ρ: 0.58), liver stiffness (ρ: 0.67) and enhanced liver fibrosis test (ρ: 0.64) (all p < 0.001). GDF-15 was higher in patients with detectable bacterial DNA in blood (3520 vs. 2250 pg/mL; p < 0.001) and correlated with lipopolysaccharide (ρ: 0.34; p = 0.010) and lipoteichoic acid (ρ: 0.37; p = 0.004). Platelet activation was not linked to GDF-15 after adjusting for liver disease severity, yet patients with undetectable GPIIb/IIIa activation after stimulation showed significantly higher GDF-15. Over a me...