Senescence of activated hepatic stellate cells (HSCs) is crucial for the regression of liver fibrosis. However, impaired immune clearance can result in the accumulation of senescent HSCs, exacerbating liver fibrosis. The activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is essential for both senescence and the innate immune response. Additionally, the specific delivery to activated HSCs is hindered by their inaccessible anatomical location, capillarization of liver sinusoidal endothelial cells (LSECs), and loss of substance exchange. Herein, we propose an antifibrotic strategy that combines prosenescence with enhanced immune clearance through targeted delivery of manganese (a cGAS-STING stimulator) via albumin-mediated transcytosis, specifically aimed at inducing senescence and eliminating activated HSCs in liver fibrosis. Our findings demonstrate that only albumin efficiently transfers manganese to activated HSCs from LSECs via transcytosis compared to liposomes, resulting in significant antifibrotic effects in vivo while exhibiting negligible toxicity.

We used Doppler US to evaluate the changes in hepatic arterial hemodynamics that occur following LDLT in pediatric recipients, with a view to assessing the utility of these parameters in predicting early HAT. A retrospective review of 144 pediatric recipients (73 males, 71 females) who underwent routine Doppler US in the first week after LDLT was undertaken, and changes in hepatic arterial hemodynamics were assessed. The HARI and HAPSV were compared in patients with early HAT (defined as occurring in the first postoperative week) and a control group, and the utility of these parameters in predicting early HAT after LDLT was determined. A total of 11 pediatric recipients experienced early HAT, being diagnosed on average four and a half days after LDLT. HARI and HAPSV values were significantly different between the early HAT group and controls. HARI values <0.6 on the day before the onset of early HAT were able to predict HAT development with a sensitivity of 81.8% and specificity of 95.2%. This provides evidence for routine Doppler US examination in these patients and supports consideration of more intensive anticoagulation in these high‐risk patients.

Background: Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. Methods: From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson’s correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland–Altman method were performed for agreement evaluation. Results: A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p < 0.001; ICC: 0.90, p < 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p < 0.05). Conclusions: WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation.

The purpose of this study was to investigate the effect of body mass index (BMI) on the prevalence of overt hepatic encephalopathy (OHE) after the transjugular intrahepatic portosystemic shunt (TIPS) procedure in decompensated cirrhotic patients. A retrospective observational cohort study of 145 cirrhotic patients receiving TIPS was carried out in our department from 2017 to 2020. The relationships between BMI and clinical outcomes including OHE, as well as risk factors of developing post-TIPS OHE, were analyzed. BMI was categorized as normal weight (18.5 ≤ BMI < 23.0 kg/m²), underweight (BMI < 18.5 kg/m²), and overweight/obese (BMI ≥ 23.0 kg/m²). Among the 145 patients, 52 (35.9%) were overweight/obese and 50 (34%) had post-TIPS OHE. Overweight/obese patients more frequently had OHE compared with normal weight patients (OR: 2.754, 95% CI: 1.236–6.140; p = 0.013). Overweight/obesity (p = 0.013) and older age (p = 0.030) were independent risk factors for post-TIPS OHE according to the logistic regression analysis. Kaplan–Meier curve analysis suggested that overweight/obese patients had the highest cumulative incidence of OHE (log-rank p = 0.0118). In conclusion, overweight/obesity and older age may raise the risk of post-TIPS OHE in cirrhotic patients.