The vasopressin biomarker copeptin is linked to systemic inflammation and refines prognostication in decompensated cirrhosis.
Copeptin, an arginine-vasopressin (AVP) biomarker may confer prognostic information in patients with advanced chronic liver disease (ACLD).
Methods: ACLD patients included in the Vienna Cirrhosis Study (NCT:NCT03267615) between 01/2017-04/2023 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 decompensated ACLD patients 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, while 298 were decompensated. Median levels of copeptin increased with progressive ACLD severity, (S0:7.5pmol/L vs. S5:14.3pmol/L; p<0.001). Copeptin (aB:0.10; p<0.001) was independently associated with interleukin-6 levels in dACLD. In dACLD, copeptin was linked to higher risk of further decompensation (adjusted subdistribution hazard ratio [asHR]:1.01; 95%CI:1.00-1.01; p=0.039), acute-on-chronic liver failure (ACLF; asHR:1.01; 95%CI:1.01-1.02; p<0.001) and liver-related death (LRD; asHR:1.01;95%CI: 1.01-1.02; p<0.001) independently of relevant cofactors. The MELD-copeptin score yielded higher AUROCs for liver-related events than the MELD-Na score in the internal validation cohort, accurately predicting LRD 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 LRD and ACLF 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.