Inflammation Severity Predicts ACLF, Bleeding in Acute Decompensated Cirrhosis

Hemostatic alterations may not be useful for identifying patients at risk for cirrhosis progression or bleeding events.

Systemic inflammation severity predicts risk for acute-on-chronic liver failure (ACLF) and bleeding better than coagulopathy in patients with acutely decompensated cirrhosis, according to study findings published in the Journal of Hepatology.

Researchers conducted a prospective cohort study to characterize hemostatic alterations predictive of ACLF and bleeding or thrombotic events in 169 adult patients with acute decompensated cirrhosis treated between January 1, 2020 and March 30, 2021.

Researchers performed a thorough hemostatic profiling for each patient, analyzing coagulation factors, fibrinolytic factors, and markers for fibrinolysis activation and plasmatic hypercoagulability, such as plasmin-antiplasmin (PAP) complex and endogenous thrombin potential (ETP), respectively. They also assessed the severity of systemic inflammation using C-reactive protein concentrations.

Researchers then compared results from the 169 patients with acute decompensated cirrhosis with 46 patients with stable decompensated cirrhosis and 52 patients with compensated cirrhosis, both of which served as control groups.

Patients with acute decompensation demonstrated increased hypercoagulability — indicated by ETP with thrombomodulin (TM) — compared with the 2 control groups (ETP: 871 vs 750 vs 605 nmol/L*min; P <.0001). Correspondingly, patients with acute decompensation also exhibited higher levels of Factor VIII (FVIII) and lower anticoagulant levels.

During the 1-year follow-up period, 55 patients developed ACLF, CLIF-C AD, CRP concentrations, and Child-Pugh stage independently predicted ACLF. These 3 factors combined — called the Padua model — predicted risk for ACLF after 1 year with a 74.5% sensitivity and an 83.3% specificity (area under the receiver operating characteristic [AUROC], 0.857; 95% CI, 0.798-0.915).

Higher concentrations of CRP and progression to ACLF predicted bleeding episodes, while higher concentrations of CRP and the antifibrinolytic factor, plasminogen activator inhibitor-1 (PAI-1) greater than 50mg/mL, predicted thrombosis.

“Inflammation severity, and not coagulopathy, is the most important predictor of ACLF and bleeding in AD [acutely decompensated cirrhosis],” the study authors wrote. “The Padua model can be used to identify AD [acutely decompensated cirrhosis] patients at risk of ACLF.”

The study authors emphasized that they used baseline hemostatic profiling rather than hemostatic assessments during the acutely decompensated cirrhosis or ACLF to determine the association between coagulopathy and bleeding complications. Therefore, serial hemostatic assessments may provide more information about thrombo-hemorrhagic risk in ACLF and acutely decompensated cirrhosis. Other study limitations include lack of assessment of biomarkers other than CRP to determine severity of systemic inflammation and the method the researchers used to assess coagulation. Additionally, lack of assessment of transfusions, anticoagulant therapy, recent bleeding episodes, and presence of hepatocellular carcinoma might have confounded results.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Zanetto A, Pelizzaro F, Campello E, et al. Severity of systemic inflammation is the main predictor of ACLF and bleeding in patients with acutely decompensated cirrhosis. J Hepatol. Published online September 20, 2022. doi:10.1016/j.jhep.2022.09.005