This study explored the predictive value of the monocyte-to-lymphocyte ratio (MLR) and platelet–lymphocyte ratio (PLR) in patients with acute-on-chronic liver failure (ACLF). A retrospective analysis was carried out on 40 patients with ACLF from January 2018 and August 2019 in our hospital. The patient’s clinical information during hospitalization was collected, and their survivals were followed for 3 months. MLR and PLR values of patients were compared, and the correlation between liver function indicators and prognosis was analyzed. We observed that MLR levels in the survival and death groups were 0.521 (0.311, 0.827) and 0.741 (0.442, 1.121), respectively. MLR levels were markedly enhanced in the death group compared to the survival group (P = 0.021). The receiver operating characteristic curve (ROC) exhibited that the area under the ROC curve and 95% confidence interval for the survival group was 0.641 (0.528–0.757). Survival analysis demonstrated that the 3-month survival of the high MLR group was markedly lower than that of the low MLR group (P = 0.001). Multivariate regression exposed that MLR and PLR were independent prognostic factors for ACLF. MLR and PLR could be prospective prognosticative markers of ACLF.
To investigate the association between inflammatory cytokines and liver function indices in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients and chimeric antigen receptor (CAR) T therapy recipients, with the aim of identifying prognostic biomarkers and elucidating the pathophysiological roles of inflammatory cytokines in HBV-ACLF. This retrospective cohort study analyzed clinical data from three groups: 68 patients with confirmed HBV-ACLF, 30 patients with pre-HBV-ACLF, and 372 hematologic malignancy patients receiving CAR-T therapy with preserved liver function at the First Affiliated Hospital of Soochow University. Serum interleukin (IL)-10 levels demonstrated a progressive increase across the groups [healthy controls: 0.15 (0.10;2.18) pg/mL; pre-HBV-ACLF: 3.80 (2.38;11.83) pg/mL; HBV-ACLF: 5.95 (3.90;14.75) pg/mL; p < 0.001]. Patients with clinical improvement exhibited significantly lower IL-10 concentrations and higher IL-6/IL-10 ratios compared to those with disease progression (p < 0.05). Notably, IL-6 levels remained stable across clinical stages, with HBV-ACLF patients without secondary infection showing lower IL-6 levels than pre-HBV-ACLF patients (p < 0.05). Following CAR-T therapy, hematologic patients displayed significantly elevated IL-6 levels, accompanied by increases in AST and INR prolongation, whereas TBIL and ALT remained stable (p > 0.05). Consistent with HBV-ACLF observations, improved CAR-T recipients demonstrated significantly lower IL-6/IL-10 ratios than progression patients (p < 0.05). IL-10 exhibits stage-dependent dynamics in HBV-ACLF pathogenesis and progression, closely mirroring hepatic functional deterioration. The IL-6/IL-10 ratio serves as a prognostic biomarker for both HBV-ACLF and CAR-T therapy-related liver injury, with lower ratios indicating better clinical outcomes. Not applicable.
Background: Acute liver injury (ALI) is characterized by massive hepatocyte death and has high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the pathophysiology of ALI and is involved in the inflammatory response mediated by NOD-like receptor protein 3 (NLRP3) inflammasome activation. Deltex 1 (DTX1) is a single transmembrane protein with ubiquitin E3 ligase activity and is closely involved in cell growth, differentiation, and apoptosis, as well as intracellular signal transduction. However, little is known about the influence of DTX1 on ALI. This study aimed to investigate the role of DTX1 in pyroptosis and inflammation induced by D-galactosamine (D-GalN) and tumor necrosis factoralpha (TNF-α) in human hepatocytes (LO2 cells) in vitro. Methods: Cell pyroptosis was measured by flow cytometry. The levels of DTX1, pyroptosis-associated proteins, and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Immunofluorescence staining, co-immunoprecipitation, ubiquitination, and luciferase reporter and chromatin immunoprecipitation assays were performed to detect the regulation between DTX1 and NLRP3 or hepatocyte nuclear factor 4 alpha (HNF4α). Analysis of variance was performed to compare groups. Results: We found that DTX1 was decreased in D-GalN/TNF-α-induced LO2 cells. DTX1 overexpression significantly inhibited D-GalN/TNF-α-induced cell pyroptosis and inflammation. DTX1 interacted with NLRP3 and induced NLRP3 ubiquitination and degradation. Furthermore, by targeting NLRP3, DTX1 knockdown significantly induced cell pyroptosis and inflammation. In addition, HNF4α promoted DTX1 transcription by binding with its promoter. Conclusion: Our study revealed that DTX1 suppressed D-GalN/TNF-α-induced hepatocyte pyroptosis and inflammation by regulating NLRP3 ubiquitination.
A new class of bidentate diphosphite and diphosphinite ligands has been developed from inexpensive norbornadiene. These ligands exhibited excellent enantioselectivities in the Rh(I)-catalyzed asymmetric hydrogenation of olefin derivatives (up to 99.9% ee).
Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a severe clinical syndrome with a high mortality rate. Identifying prognostic factors is therefore crucial. This study aimed to identify factors influencing the prognosis of HBV-ACLF and to construct a combined prognostic indicator. This retrospective study included 258 patients with HBV-ACLF, categorized into 2 groups based on prognosis: improvement and worsening. Baseline characteristics, biochemical parameters, and hematological indicators were compared between the 2 groups. Multiple logistic regression and a support vector machine model were applied to analyze the factors associated with prognosis. Based on the regression results, a composite indicator was developed and its predictive performance was evaluated using receiver operating characteristic curve analysis. The incidence of complications such as advanced age, esophageal varices, severe jaundice, and severe ascites was significantly higher in the prognosis worsening group than in the improvement group. Biochemical and hematological indicators such as ammonia (NH₃), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly elevated in the worsening group, while albumin levels were significantly lower compared with the improvement group. Analysis indicated that ALT, AST, LDH, NH₃, and model for end-stage liver disease score were most strongly associated with prognosis. The receiver operating characteristic curve of the combined indicator showed an area under the curve of 0.749, outperforming any single indicator. In addition, the combined index was significantly negatively correlated with the length of hospital stay. ALT, AST, LDH, NH₃, and model for end-stage liver disease score are key prognostic factors in patients with HBV-ACLF. The combined indicator constructed from these variables demonstrates good predictive value for clinical outcomes and length of hospital stay, and may provide useful guidance for clinical decision-making.