Aims. Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods. Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results. Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR>16.26ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions. Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients.

Background: Acute-on-chronic liver failure (ACLF) has high short-term mortality and lacks sufficient medical therapy. Available algorithms are unable to precisely predict short-term outcomes or safely stratify patients with ACLF as emergent liver transplantation candidates. Therefore, a personalized prognostic tool is urgently needed. Purpose: Platelet function and its clinical significance in ACLF patients with chronic hepatitis B virus (HBV) infection have not been investigated. This study aimed to assess changes in platelet function using thromboelastography (TEG) and platelet mapping (TEG-PM) in HBV-related ACLF patients. Methods: Chronic liver disease patients with acute decompensation or acute hepatic injury were recruited. The derivation cohort enrolled HBV-related patients at Nanfang Hospital. HBV-related and non-HBV-related patients were both enrolled in internal and external validation cohorts at seven university hospitals. TEG and TEG-PM were performed at baseline in the derivation cohort and baseline, day 7, and day 14 in the validation cohorts. The primary outcome was all-cause 28-day mortality. Status check and new-onset complications were recorded during the 3-month follow-up, but status check will extend to 5 years. Conclusion and Future Plans: In this study, 586 participants were enrolled, including 100 in derivation cohort, 133 in internal validation cohort, and 353 in external validation cohort. Biomaterials, including plasma, serum, urine, and some explanted liver tissues, were collected from these patients. A 3-month follow-up with survival status was completed. The baseline characteristics indicated that 51% of the patients had adenosine diphosphate (ADP)-hyporesponsive circulating platelets. The prognostic potential of platelet function will be explored in the derivation cohort (HBV-related ACLF patients) and further substantiated in the validation cohorts (HBV-related and non-HBV-related ACLF patients). Biosamples are currently used to explore the underlying mechanisms related to ADP-hyporesponsive platelets. The ongoing proteomic and metabolic analyses will provide new insights into the pathogenesis of extrahepatic organ failures in ACLF patients.