Lukas Hartl, Marlene Hintersteininger, Benedikt Simbrunner, Mathias Jachs, Benedikt Silvester Hofer, David Josef Maria Bauer, Nina Dominik, Michael Schwarz, Lorenz Balcar, Georg Kramer, Annarein J C Kerbert, Minneke J Coenraad, Thierry Thevenot, Richard Moreau, Jonel Trebicka, Joan Clària, Rodrig Marculescu, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
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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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>In patients with dACLD, copeptin is independently linked to systemic inflammation. 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引用次数: 0
摘要
背景与目的：精氨酸-抗利尿素（AVP）生物标志物Copeptin可能为晚期慢性肝病（ACLD）患者提供预后信息。方法：前瞻性招募2017年1月1日至2023年4月纳入维也纳肝硬化研究（NCT:NCT03267615）和可用copeptin水平的ACLD患者，并将其分为6个预定义的临床ACLD阶段，从S0（亚临床门静脉高压）到S5（进一步失代偿）。在衍生队列（n=150）中制定了失代偿ACLD患者的预后评分（MELD-copeptin评分），并在内部（n=148）和外部验证队列（n=771）中进行了验证。结果：475例ACLD患者中代偿性177例，失代偿性298例。copeptin的中位水平随着ACLD严重程度的加重而升高，(50:7 .5pmol/L vs. 55:14 .3pmol/L；结论：在dACLD患者中，copeptin与全身性炎症独立相关。MELD-copeptin评分可识别有临床预后受损风险的dld患者。
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.
期刊介绍：
Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion.
As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.
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