Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0

Abstract

BackgroundThe clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll‐like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute‐on‐chronic liver failure (ACLF).MethodsPatients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and evaluated predictors of ACLF.ResultsOne hundred and seventy three patients with AD were included (median MELD: 18; CLIF‐C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674 ng/L vs. 310 ng/L vs. 157 ng/L; p < 0.001). In patients with AD, Child–Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow‐up, 52 patients developed ACLF (median time from recruitment: 66 days). PSP, CLIF‐C AD score, and Child–Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780–0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF‐C AD <50, a PSP >674 ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis.ConclusionThe Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD.

Predicting the development of acute‐on‐chronic liver failure

“…introduced the Padua model 2.0 that identifies patients with AD at a high risk of developing ACLF. 4 This expands on the authors' previous work on the original Padua model, which combined C‐reactive protein (CRP), Chronic Liver Failure Consortium AD score (CLIF‐C AD) and Child Pugh score to predict risk of ACLF in patients with AD, and this model could more accurately predict ACLF development than Model for End‐Stage Liver Disease (MELD), CLIF‐C AD or Child Pugh scores alone. 5 The Padua model 2.0 differs in that CRP is replaced by presepsin (PSP), a soluble fragment of CD14, as the authors found that high levels of PSP characterised patients with AD.…”

Acute decompensation of cirrhosis versus acute‐on‐chronic liver failure: What are the clinical implications?

“…In this version, CRP was substituted with Presepsin (PSP), a soluble fragment of CD14, expressed by monocytes and macrophages, released during the inflammatory response. PSP demonstrated a stronger correlation with the risk of ACLF development compared with CRP 42 . The improved specificity of PAMPs‐related inflammation is believed to account for the greater performance of Padua 2.0 compared to the Padua model.…”

“…PSP demonstrated a stronger correlation with the risk of ACLF development compared with CRP. 42 The improved specificity of PAMPs‐related inflammation is believed to account for the greater performance of Padua 2.0 compared to the Padua model. If further confirmed, the Padua and Padua 2.0 models could serve as important tools for identifying at‐risk patients who require urgent evaluation for LT and for targeting a population suitable for the development of disease‐modifying drugs.…”

Profiling plasma alterations of extracellular vesicles in patients with acutely decompensated cirrhosis and bacterial infection

“…8 The release of EVs in decompensated cirrhosis is due to systemic inflammation, chronic liver injury and complications of cirrhosis such as acute kidney injury (AKI). 9,10 Since these events are responsible for hepatic decompensation and/or development of acute-on-chronic liver failure (ACLF), [11][12][13] a recent hypothesis suggests that the determination of plasmatic EVs, particularly the ones derived from hepatocytes, 10,14 could improve prognostic stratification. [14][15][16][17] Bacterial infections are common complications in decompensated cirrhosis, occurring in 30%-40% of hospitalized patients.…”