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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. [ABSTRACT FROM AUTHOR]

Background and Aim: Tri‐typing of acute‐on‐chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. Methods: Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. Results: Compared with type‐B (n = 262, compensated cirrhosis) and type‐C (n = 129, decompensated cirrhosis) ACLF, type‐A patients (n = 195, non‐cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type‐A, while bacterial infections in type‐B and type‐C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type‐A compared with type‐B or type‐C ACLF patients. Kidney failure was predominantly identified in type‐C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type‐C ACLF showed the highest 28‐day (65.2%) and 90‐day (75.3%) mortalities, compared with type‐A (48.7% and 54.4%, respectively) and type‐B (48.4% and 62.8%, respectively) ACLF cases. Compared with type‐A (11.7%) ACLF patients, the increased mortality from 28 to 90 days was higher in type‐B (31.6%) and type‐C (37.5%). Conclusion: Tri‐typing of HBV‐related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short‐term prognosis in ACLF patients. [ABSTRACT FROM AUTHOR]

Toll-like receptor 2 (TLR2) plays an important role in the immunopathogenesis of hepatitis B virus (HBV) infection. The relationship between TLR2 expression and clinical outcome of chronic HBV infection is not yet elucidated in details so far. Here, we employed clinical cohorts to investigate TLR2 expression and function in different phases of HBV infection and dynamic changes of TLR2 expression in HBeAg-positive chronic hepatitis B (CHB) patients during antiviral therapy. TLR2 was mainly expressed in monocytes and its ligand stimulation resulted in TNF-α, IL-6 and IL-10 production. Serum soluble TLR2 (sTLR2) levels were negatively correlated with TLR2 mRNA in PBMCs. As compared with immunotolerant carriers and inactive carriers, CHB patients showed an elevated TLR2 expression and TNF-α, IL-6 induction in PBMC, but had a decreased level of sTLR2 in serum. However, TLR2 expression and TNF-α induction in monocytes of CHB patients remained lower than healthy controls. Furthermore, higher TLR2 expression in PBMCs and lower level of sTLR2 in serum at baseline were predictive of a complete response to 52 weeks of telbivudine (LdT) therapy. Temporal dynamic analysis showed that TLR2 expression was restored with viral suppression and ALT normalization from week 12 to 24. However, peg-IFN-α-2a therapy induced a slightly decline in TLR2 expression. In conclusion, TLR2 expression and function in monocytes were impaired by chronic HBV infection. Higher TLR2 expression in PBMC and lower level of sTLR2 in serum at baseline were associated with a complete response to LdT therapy, and dynamic TLR2 expression was differently regulated by LdT and peg-IFN-α-2a therapy. [ABSTRACT FROM AUTHOR]

Keywords: Hepatitis B virus; Acute-on-chronic liver failure; Prognosis EN Hepatitis B virus Acute-on-chronic liver failure Prognosis 479 480 2 12/30/20 20210201 NES 210201 To the Editor: We read the paper "The PREDICT study uncovers three clinical courses in acutely decompensated cirrhosis with distinct pathophysiology" published in Journal of Hepatology with great interest.[1] This multicenter study reported on 3 different clinical courses with distinct pathophysiology and prognosis in patients with acute decompensation (AD) of cirrhosis. Clinical and laboratory characteristics of the pre-ACLF patients (n = 90), ACLF patients at the time of admission (n = 189) and patients with AD without ACLF development (n = 587) were compared in Table 1. The prevalence of HBV reactivation was different (p <0.001) among these patients and higher in pre-ACLF patients (56.7%) and ACLF patients (57.7%). [Extracted from the article]