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

Summary 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: 0.68–0.93; p = 0.004) and liver‐related death (asHR: 0.76; 95% CI: 0.63–0.91; p = 0.004). Conclusion Decreased levels of IGF‐1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF‐1 was independently linked to high BMI. Lower IGF‐1 in cirrhosis predicts decompensation, ACLF and liver‐related death.