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Research Article: APASL-ACLF without previous decompensation is immunologically distinct from EASL-CLIF-ACLF with previous decompensation

Date Published: 2026-10-06

Abstract:
Definitions of acute-on-chronic liver failure (ACLF) differ, with a focus on extrahepatic organ failures on the basis of previously compensated or decompensated cirrhosis in EASL-CLIF-ACLF versus hepatic failure in patients without previous decompensation in APASL-ACLF. Here, we explored whether patterns of systemic inflammation and immune cell alterations differ between these types of ACLF. Consecutive patients with acute decompensation, EASL-CLIF- or APASL-ACLF were recruited from two liver centres. Patterns of systemic inflammation were characterized by Olink analysis and changes in circulating immune cells by flow cytometry. A total of 374 patients with acute decompensation (AD) were identified, of whom 56 fulfilled exclusively the EASL-CLIF-definition of ACLF (15% of all patients), while only 19 patients (5.1% of all patients) met exclusively the APASL-definition. APASL-ACLF was associated with higher bilirubin, lower creatinine, higher INR and higher hemoglobin concentrations compared to EASL-ACLF. Patterns of systemic inflammation differed between EASL-CLIF and APASL-ACLF. For example, FGF-23, IL-17 or VEGF-A were associated with EASL-CLIF-ACLF, while FGF-19 or low IL-12 were associated with APASL-ACLF. Moreover, patients with EASL-CLIF-ACLF had significantly lower counts of CD8+ T cells, while in APASL-ACLF a reduction of CD4+ T cell was characteristic. Detailed immune cell phenotyping revealed distinct expression of co-stimulatory molecules, inhibitory molecules and T cell activation markers in APASL-ACLF compared to patients with AD or EASL-CLIF-ACLF. We provide preliminary evidence that EASL-CLIF- and APASL-ACLF are associated with different changes in systemic inflammation patterns and immune cell phenotypes, suggesting that both types of ACLF might be pathophysiologically different.

Introduction:
Definitions of acute-on-chronic liver failure (ACLF) differ, with a focus on extrahepatic organ failures on the basis of previously compensated or decompensated cirrhosis in EASL-CLIF-ACLF versus hepatic failure in patients without previous decompensation in APASL-ACLF. Here, we explored whether patterns of systemic inflammation and immune cell alterations differ between these types of ACLF.

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