Insulin‐like growth factor‐1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver‐related mortality

作者：Lukas Hartl, Michael Schwarz, Benedikt Simbrunner, Mathias Jachs, Peter Wolf, David Bauer, Bernhard Scheiner, Lorenz Balcar, Georg Semmler, Benedikt Hofer, Nina Dominik, Rodrig Marculescu, Michael Trauner, Mattias Mandorfer, Thomas Reiberger · 发表于：Alimentary Pharmacology & Therapeutics · 年份：2024 · DOI：10.1111/apt.18289 · 被引用次数：14 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation

BACKGROUND AND AIMS: We aimed to characterise insulin-like growth factor-1 (IGF-1) signalling in patients with advanced chronic liver disease (ACLD). METHODS: Consecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6-9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non-bleeding hepatic decompensation and S5: further decompensation. RESULTS: In total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF-1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p < 0.001). Patients with CSPH had significantly lower IGF-1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF-1 showed an independent negative association with body mass index (BMI; aB: -1.56; p < 0.001), enhanced liver fibrosis (ELF) test (aB: -8.43; p < 0.001), MELD (aB: -1.13; p = 0.042) and age (per 10 years; aB: -6.87; p < 0.001). IGF-1 exhibited an excellent AUROC (0.856) for the prediction of liver-related death at 6 months of follow-up. Lower IGF-1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95% CI: 0.83-0.98; p = 0.016), acute-on-chronic liver failure (ACLF; asHR: 0.80; 95% CI: 0....