Purpose: This study aimed to investigate the efficacy of preoperative aspartate aminotransferase-to-platelet-ratio index (APRI) score to predict the risk of posthepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) after liver resection, and to compare the discriminatory performance of the APRI with the Child–Pugh score, model for end-stage liver disease (MELD) score, and albumin–bilirubin (ALBI) score. Patients and methods: A total of 1,044 consecutive patients with HCC who underwent liver resection were enrolled and studied. Univariate and multivariate analyses were performed to investigate risk factors associated with PHLF. Predictive discrimination of Child–Pugh, MELD, ALBI, and APRI scores for predicting PHLF were assessed according to area under the ROC curve. The cutoff value of the APRI score for predicting PHLF was determined by ROC analysis. APRI scores were stratified by dichotomy to analyze correlations with incidence and grade of PHLF. Results: PHLF occurred in 213 (20.4%) patients. Univariate and multivariate analyses revealed that Child–Pugh, MELD, ALBI, and APRI scores were significantly associated with PHLF. Area under the ROC analysis revealed that the APRI score for predicting PHLF was significantly more accurate than Child–Pugh, MELD, or ALBI scores. With an optimal cutoff value of 0.55, the sensitivity and specificity of the APRI score for predicting PHLF were 72.2% and 68.0%, respectively, and the incidence and grade of PHLF in patients with high risk (APRI score >0.55) was significantly higher than in the low-risk cohort (APRI score <0.55). Conclusion: The APRI score predicted PHLF in patients with HCC undergoing liver resection more accurately than Child–Pugh, MELD, or ALBI scores.

Misregulation of the p53-mdm2 loop function is a major mechanism to promote hepatocellular carcinoma (HCC). RBM38, a member of the RNA recognition motif (RRM) family of RNA binding proteins (RBPs), plays a fundamental role in the posttranscriptional control of gene expression and regulatory functions in human tumors. A novel RBM38-p53-mdm2 autoregulatory feedback loop has been demonstrated. However, its mechanistic role in HCC remains unclear. In the present study, we investigated the role and molecular mechanism of misregulation in the p53-mdm2 loop function by RBM38 in HCC. First we investigated the correlation of RBM38 activity and p53-mdm2 loop function in liver cancer cells and HCC tissues by western blot and quantitative RT-PCR. We then conducted functional assays to investigate the molecular roles of RBM38 in inhibiting liver cancer cells aggressiveness in vitro and suppressing tumorigenicity in vivo. We observed RBM38 protein expression was commonly silenced coupled with increased mdm2 and decreased wild type (wt) p53 in liver cancer cells and HCC tissues compared to the corresponding normal liver cells and adjacent liver tissues. RBM38 mRNA level was significantly lower in HCC than adjacent liver tissues, whereas mdm2 and wtp53 mRNA levels were similar between HCC and adjacent liver tissues. This implied that deactivation of RBM38 could disrupt the p53-mdm2 loop and promote HCC, even though p53 and mdm2 transcript amounts were stable. Then, we generated stable liver cancer cell lines with overexpressed RBM38 (RBM38-OE) and found that up-regulation of RBM38 could inhibit mdm2 and restore wtp53 expression. Luciferase assay shown that RBM38 destabilized the mdm2 transcript through binding to multiple AU-/U-rich elements in mdm2 3’-UTR. Furthermore, functional assays showed that ectopic expression of RBM38 could induce liver cancer cell apoptosis and senescence, inhibit proliferation and colony growth, and suppress migration and invasion in vitro. Lastly, RBM38 could suppress HCC tumorigenicity in vivo. Our findings suggested that RBM38 may be a core contributor in stabilizing the p53-mdm2 loop function to prevent HCC, and a potential novel target to provide a therapeutic strategy for HCC by inhibiting mdm2 and rescuing p53 from inactivation.

Purpose: This research aims to develop prognostic nomograms to predict tumor recurrence and recurrence-free survival (RFS) in individuals with initially unresectable hepatocellular carcinoma (uHCC) who were later subjected to conversion hepatectomy following lenvatinib, PD-1 inhibitors, and interventional (LPI) therapy.Methods: We performed a retrospective review of clinical information from 150 individuals diagnosed with HCC who underwent conversion hepatectomy following LPI therapy between November 2019 and December 2024. Independent predictors linked to recurrence and RFS were identified through comprehensive univariate and multivariate analyses, and the identified factors were subsequently integrated into nomogram models. Receiver operating characteristic (ROC) curves, calibration plots, and the concordance index (C-index) were employed to evaluate the predictive performance of the nomograms.Results: Our investigation identified several key risk factors for recurrence, including age, tumor number, tumor differentiation, preoperative prognostic nutritional index (PNI), preoperative systemic immune-inflammation index (SII), and postoperative protein induced by vitamin K absence or antagonist-II (PIVKA-II) level. For RFS, significant predictors included tumor number, tumor differentiation, preoperative SII, postoperative PIVKA-II, and postoperative alpha-fetoprotein (AFP) levels. The nomograms exhibited strong predictive performance, achieving a C-index of 0.837 (95% CI: 0.775–0.896) for recurrence prediction and 0.837 (95% CI: 0.788–0.886) for RFS. Our nomogram for recurrence prediction outperformed traditional staging systems like China Liver Cancer (CNLC) staging and Barcelona Clinic Liver Cancer (BCLC). Calibration curves and discriminative ability assessments confirmed the nomograms’ reliability in predicting actual outcomes and stratifying patients into distinct prognostic subgroups with significant RFS differences across risk categories.Conclusions: The nomogram models established in this research provide an exceptionally accurate and individualized method for predicting recurrence and RFS in initially uHCC patients undergoing LPI-based conversion hepatectomy, potentially aiding clinicians in devising tailored treatment plans and enhancing patient outcomes.

Over the past few years, the prevalence of high‐fructose diets has become a significant inducer of metabolic dysfunction‐associated steatotic liver disease (MASLD). The effects and pathological mechanisms of high dietary fructose on gut microbiota and its subsequent role in MASLD remain unclear. Here, we investigated the impact of fructose supplementation on MASLD progression in wild‐type C57BL/6 mice using both high‐fructose drinking water and a high‐fructose diet. Through 16S rDNA sequencing, we observed that long‐term fructose exposure significantly reduced the abundance of Lactobacillus murinus ( L. murinus ) in the intestines of mice. We aim to further elucidate the role and underlying mechanisms of L. murinus in high‐fructose‐induced MASLD. Logically, we supplemented L. murinus exogenously in the high‐fructose mouse model and found that L. murinus significantly alleviated fructose‐induced MASLD symptoms, characterized by reduced liver ballooning, inflammation, hepatic cholesterol, triglycerides, as well as decreased blood cholesterol, triglycerides, ALT and AST levels. To further investigate the mechanistic basis of L. murinus ‐mediated protection, we conducted serum and fecal metabolomic analyses. These studies identified arginine as the sole metabolite exhibiting marked reductions in both serum and intestinal compartments. Integrated multi‐omics analysis revealed a strong positive correlation between gut L. murinus abundance and arginine levels. ELISA demonstrated that exogenous administration of L. murinus effectively restored circulating arginine concentrations in high‐fructose‐fed mice. Importantly, direct arginine supplementation produced similar therapeutic benefits as L. murinus . Specifically, it improved key features of MASLD, including reduced liver ballooning, less liver inflammation, lower buildup of cholesterol and triglycerides in the liver and blood, and decreased ALT/AST levels. These data revealed a novel mechanism underlying fructose‐induced MASLD by decreasing the abundance of gut L. murinus , which disrupts arginine metabolism. L. murinus and arginine could serve as potential therapeutic strategies against fructose‐induced MASLD.