Pyroptosis has an important role in liver inflammation and fibrosis. The role of KC pyroptosis in liver fibrosis was unclear. Ursolic acid (UA) has antifibrotic effects, but study on the effect and mechanism of UA on KC pyroptosis in liver fibrosis has not been reported. Therefore, we induced KC pyroptosis using Lipopolysaccharide (LPS) and nigericin (Nig) in vitro. C57BL/6J mice were intraperitoneally injected with carbon tetrachloride (CCl₄) to establish a liver fibrosis model. We demonstrated that UA attenuated CCl₄-induced liver fibrosis, liver damage, and KC pyroptosis of liver tissue. Moreover, KCs were treated with UA and small interfering RNA of NOX2, which showed that inhibiting the NOX2/NLRP3 inflammasome signaling pathway attenuated KC pyroptosis and UA abrogated this effect via suppressing this pathway in vitro. Furthermore, mice were treated with UA, GSK2795039 (a specific inhibitor of NOX2) or MCC950 (a specific inhibitor of NLRP3). Compared with inhibiting NOX2 alone, inhibiting NOX2 in the presence of UA did not markedly ameliorate KC pyroptosis of liver tissue in CCl₄-induced liver fibrosis. In addition, when NLRP3 was silenced or inhibited, the result was similar to that of knocking down NOX2 in vivo and in vitro. These results indicate that UA attenuates liver fibrosis in mice via inhibiting KC pyroptosis, which may be through the suppression of NOX2/NLRP3 inflammasome signaling pathway. It may be a new target for treating liver fibrosis and provide a new theoretical basis for the use of UA to treat liver fibrosis.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation, leading to high short-term mortality. The lymphocyte to high-density lipoprotein ratio (LHR) has been introduced as a novel marker of inflammation. However, its role as a prognostic inflammatory biomarker in the context of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) has received limited attention. We retrospectively included 272 patients with HBV-ACLF who met the definition of APALC. Data on clinical features and laboratory tests were collected from medical records within 24 h. Logistic regression was used to identify risk factors for poor short-term prognosis, and LHR-based prediction (LHRB) models were constructed based on risk factors. Furthermore, the accuracy of the LHRB model was validated through rigorous testing. In the survival and death groups, there were statistical differences in their CTP, MELD, MELD-Na, COSSH-ACLF II scores, and LHR. Multivariate logistic regression identified seven predictors significantly associated with 28-day mortality. Furthermore, statistically significant differences in short-term mortality and certain clinical laboratory tests for poor prognosis were observed between the high and low LHR groups. To assess the predictive performance of various models in terms of short-term mortality, the area under the receiver operating characteristic curve (AUROC) was calculated. The AUROC values for the CTP, MELD, MELD-Na, COSSH-ACLF II, and LHRB models were found to be 0.725, 0.788, 0.772, 0.871, and 0.877, respectively. The results in the validation group were similar to those in the training group, and the validation results suggested excellent performance of the LHRB model. LHR levels have the potential to serve as indicators for the prognosis of HBV-ACLF. Additionally, the recently developed LHRB model offers an accessible risk assessment tool.

Background. Cirrhosis esophageal variceal rebleeding is a major complication of chronic cirrhosis. The hepatic venous pressure gradient (HVPG) can predict the risk of rebleeding in patients with cirrhosis and has a good correlation with liver stiffness measurement (LSM). However, there are currently few studies based on liver stiffness to predict the risk of rebleeding in patients with liver cirrhosis. This study is aimed at exploring whether liver stiffness can predict rebleeding in patients with hepatitis B virus-related cirrhosis and developing an easy-to-use nomogram for predicting the risk of rebleeding in patients with liver cirrhosis undergoing secondary prevention. Methods. A prospective analysis of 289 cirrhosis patients was performed. Univariate and multivariate analyses were used to identify independent prognostic factors to create a nomogram. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots. Results. Use of a nonselective beta-blocker (NSBB) drug, LSM, hemoglobin, and platelet count were identified as factors that could predict rebleeding. We created a nomogram for rebleeding in cirrhosis by using these risk factors. The predictive ability of the nomogram was assessed by the -index (0.772, 95% CI 0.732–0.822). The results of the calibration plots showed that the actual observation and prediction values obtained by the nomogram had good consistency. Conclusions. LSM can predict the risk of rebleeding in patients with cirrhosis, while the nomogram is a conventional tool for doctors to facilitate a personalized prognostic evaluation.