The Vasopressin Biomarker Copeptin is Linked to Systemic Inflammation and Refines Prognostication in Decompensated Cirrhosis

Background & Aims: Copeptin, an arginine-vasopressin biomarker, may confer prognostic information in patients with advanced chronic liver disease (ACLD). Methods: Patients with ACLD included in the Vienna Cirrhosis Study (NCT03267615) between January 2017 and April 2023 and available copeptin levels were prospectively recruited and classified into 6 predefined clinical ACLD stages from S0 (subclinical portal hypertension) to S5 (further decompensation). A prognostic score (MELD-copeptin score) in patients with decompensated ACLD (dACLD) was developed in a derivation cohort (n = 150) and validated in an internal (n = 148) and an external validation cohort (n = 771). Results: Among 475 patients with ACLD, 177 were compensated, whereas 298 were decompensated. Median levels of copeptin increased with progressive ACLD severity (S0, 7.5 pmol/L vs S5, 14.3 pmol/L; P <.001). Copeptin (adjusted Beta, 0.10; P <.001) was independently associated with interleukin-6 levels in dACLD. In dACLD, copeptin was linked to higher risk of further decompensation (adjusted subdistribution hazard ratio, 1.01; 95% confidence interval, 1.00–1.01; P =.039), acute-on-chronic liver failure (adjusted subdistribution hazard ratio, 1.01; 95% confidence interval, 1.01–1.02; P <.001), and liver-related death (adjusted subdistribution hazard ratio, 1.01; 95% confidence interval, 1.01–1.02; P <.001) independently of relevant cofactors. The MELD-copeptin score yielded higher area under the receiver operating characteristics (AUROCs) for liver-related events than the MELD-Na score in the internal validation cohort, accurately predicting liver-related death at 6 months (AUROC, 0.777 vs MELD-Na, 0.673), 1 year (AUROC, 0.784 vs MELD-Na, 0.661), and 2 years of follow-up (AUROC, 0.741 vs MELD-Na, 0.636). Similarly, the MELD-copeptin score consistently yielded higher AUROCS for the development of liver-related death and acute-on-chronic liver failure at 3, 6, and 12 months of follow-up in the external validation cohort. Conclusions: In patients with dACLD, copeptin is independently linked to systemic inflammation. The MELD-copeptin score identifies patients with dACLD at risk for impaired clinical outcomes.