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.