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Background and Aim: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with high short-term mortality.Effective biomarkers are required for its early diagnosis and prognosis.This study aimed to determine the diagnostic and prognostic value of thrombomodulin (TM) in patients with HBV-ACLF.Methods: The expression of TM during disease progression was evaluated through transcriptomics analysis.The plasma TM concentrations of 393 subjects with HBV-ACLF (n=213), acute-on-chronic hepatic dysfunction (ACHD, n=50), liver cirrhosis (LC, n=50) or chronic hepatitis B (CHB, n=50), and normal controls (NC, n=30) from a prospective multicenter cohort, were measured to verify the diagnostic and prognostic significance of plasma TM for HBV-ACLF patients by enzyme-linked immunosorbent assay (ELISA).Results: TM mRNA was highly expressed in the HBV-ACLF group compared with the ACHD group (AUROC=0.710).High expression of TM predicted poor prognosis for HBV-ACLF patients at 28/90 days (AUROCs=0.823/0.788).Functional analysis showed that TM was significantly associated with complement activation and the inflammatory signaling pathway.External validation confirmed its high diagnostic accuracy for HBV-ACLF patients (AUROC=0.796).Plasma TM concentrations were correlated with organ failure, including coagulation and kidney failure.Plasma TM concentrations showed a potential prognostic value for 28-day mortality rates (AUROC=0.702).Risk stratification specifically identified HBV-ACLF patients with a high risk of death as having a plasma TM concentration of ≥8.4 ng/mL.Conclusion: This study reveals that the plasma TM can be a candidate biomarker for early diagnosis and prognosis of HBV-ACLF, and might play a vital role in coagulation and inflammation.
Zhou et al. (Fri,) studied this question.