Indocyanine Green Clearance Correlates With Biomarkers Reflecting Key Disease‐Driving Mechanisms in Advanced Chronic Liver Disease and Predicts Acute‐on‐Chronic Liver Failure and Death

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BACKGROUND: Indocyanine green (ICG) clearance, determined by venous sampling, has shown promising results in the diagnosis of clinically significant portal hypertension (CSPH) in compensated advanced chronic liver disease (cACLD) and prognostication in decompensated ACLD (decompensated cirrhosis). Data on ICG clearance measurement by pulse dye densitometry (PDD) via finger clip are comparatively scarce. AIMS: To evaluate the diagnostic (CSPH) and prognostic utility of ICG clearance throughout ACLD stages. METHODS: ACLD (liver stiffness ≥ 10 kPa) patients undergoing same-day hepatic venous pressure gradient (HVPG) measurement and ICG clearance assessment via PDD in 2017-2022 were recruited from the prospective Vienna Cirrhosis Study (VICIS, NCT03267615). RESULTS: Two hundred and sixty-one ACLD patients (cACLD: n = 115, decompensated cirrhosis: n = 146) were included. Among cACLD patients (CSPH: 62.4%), ICG retention 15 min (ICG-R15) correlated moderately with HVPG (Spearman's rho:0.458; p < 0.001) and yielded a suboptimal diagnostic accuracy for CSPH (AUROC: 0.687 [95% CI: 0.585-0.789]). ICG-R15 showed a strong correlation with the model for end-stage liver disease score (rho: 0.701; p < 0.001) and correlated with biomarkers of endothelial dysfunction (von Willebrand factor), systemic inflammation (C-reactive protein, procalcitonin, interleukin 6) and extracellular matrix remodelling (enhanced liver fibrosis test). In decompensated cirrhosis, ICG-R15 additionally correlated with mean arterial pressure, serum sodium and renin levels. ICG-R15 predicted decompensation (subdistribution hazard ratio [SHR]: 1.042 [95% CI: 1.008-1.077] per %; p = 0.014) in cACLD and independently predicted ACLF/liver-related mortality in decompensated cirrhosis (adjusted SHR: 1.062 [95% CI: 1.025-1.100] per %; p < 0.001). CONCLUSIONS: ICG-R15 by PDD correlates with portal hypertension and systemic inflammation/circulatory dysfunction as key disease-driving mechanisms in ACLD. While showing insufficient discrimination for CSPH, ICG-R15 independently predicted ACLF/liver-related mortality in decompensated cirrhosis.

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