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| Journal of hepatology. 2022 Sep 20. pii: S0168-8278(22)03110-5. doi: 10.1016/j.jhep.2022.09.005 |
| Severity of systemic inflammation is the main predictor of ACLF and bleeding in patients with acutely decompensated cirrhosis. |
| Zanetto A1, Pelizzaro F2, Campello E3, Bulato C4, Balcar L5, Gu W6, Gavasso S7, Saggiorato G8, Zeuzem S9, Russo FP10, Mandorfer M11, Reiberger T12, Trebicka J13, Burra P14, Simioni P15, Senzolo M16 |
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Abstract BACKGROUND & AIMS: Hypercoagulability and hypofibrinolysis in acutely decompensated cirrhosis (AD) may be implicated in disease progression and hemostatic complications. We conducted a prospective study to: [1] characterize hemostatic alterations in AD; [2] evaluate whether such alterations can predict ACLF and bleeding/thrombosis. METHODS: Hospitalized patients with AD were prospectively recruited and underwent an extensive hemostatic profiling including coagulation factors, thrombomodulin-modified thrombin generation assay with evaluation of endogenous thrombin potential (ETP; marker for plasmatic hypercoagulability), fibrinolytic factors, and plasmin-antiplasmin complex (fibrinolysis activation marker). Inflammation severity was assessed by C-reactive protein (CRP). In study part 1, we compared hemostasis in AD vs. controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and investigated predictors of ACLF and bleeding/thrombosis. RESULTS: 169 AD patients were recruited (median MELD 20; CLIF-C AD 54). Compared to controls, AD was associated with more pronounced hypercoagulability (ETP: 871 vs. 750 vs. 605 nmol/L*min; p<0.0001), without differences in fibrinolysis activation. During follow-up, 55 patients developed ACLF. CLIF-C AD, CRP, and Child-Pugh were independently associated with ACLF. A predictive model combining these variables (Padua model) accurately identified patients at higher risk of ACLF (AUROC 0.857; 95% CI; 0.798-0.915; sensitivity 74.5%, specificity 83.3%). Notably, CRP and progression to ACLF, but not baseline coagulopathy, were associated with bleeding (n=11); CRP and antifibrinolytic factor PAI-1 >50 ng/mL were associated with thrombosis (n=14). The prognostic value of the Padua model was validated in an independent, bicentric European cohort (n=301). CONCLUSION: Inflammation severity, and not coagulopathy, is the most important predictor of ACLF and bleeding in AD. The Padua model can be used to identify AD patients at risk of ACLF. TRIAL REGISTRATION NUMBER: NA. |
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Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
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KEYWORDS: acute-on-chronic liver failure, bleeding, coagulation, fibrinolysis, thrombosis |
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Publikations ID: 36150575 Quelle: öffnen |
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