Metabolic dysfunction-associated steatotic liver disease (MASLD) can progress to metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, contributing to a heavier global health burden. Non-invasive diagnostic tools developed using machine learning (ML) and deep learning (DL), two representative artificial intelligence algorithms, are increasingly being explored for MASH and its related fibrosis assessment. This study aimed to compare the diagnostic performance of different ML and DL models and identify the top-performing models for diagnosing MASH and associated liver fibrosis. A systematic review and meta-analysis were conducted across PubMed, Web of Science, Embase and Cochrane Library from inception to May 18, 2025. Pooled area under the receiver operator characteristic curve (AUROC) values with 95 % confidence interval (CI) were calculated. Accuracy, specificity, sensitivity, positive predictive values, and negative predictive values were also recorded. Of 4,314 studies initially identified, 106 met the inclusion criteria, with 35 studies (ML: n=28; DL: n=7) providing data for analysis. Logistic Regression and Neural Network are the most commonly algorithms applied in ML and DL, respectively. The pooled AUROCs for diagnosing MASH were 0.833 (95 %CI: 0.806-0.860) for ML models and 0.841 (95 %CI: 0.782-0.900) for DL models. Light Gradient Boosting Machine (LightGBM) and ResNet50 were the best-performing models for diagnosing MASH within ML and DL algorithms, respectively, achieving corresponding AUROCs of 0.920 (95 %CI: 0.916-0.924) and 0.960 (95 %CI: 0.951-0.969). For fibrosis diagnosis, ML models had a pooled AUROC of 0.826 (95 %CI: 0.792-0.860), with Categorical Boosting (CatBoost) achieving the highest AUROC of 0.960 (95 %CI: 0.950-0.970). DL models yielded the pooled AUROC of 0.875 (95 %CI: 0.816-0.934) for fibrosis diagnosis. Both ML and DL models demonstrated strong diagnostic performance for MASH and liver fibrosis, with DL achieving marginally higher AUROCs. AI-driven approaches show promise in MASLD management.

Sepsis is characterized as a life-threatening organ dysfunction resulting from a dysregulated host response to infection, representing a critical clinical syndrome. Uncontrolled infection and inflammation are two main characteristics of sepsis. Neutrophil extracellular traps (NETs) is a major mechanism by which neutrophils resist pathogens invasion, but the mechanism of the NETs formation remain completely unclear. This study aims to elucidate the role of Histone Deacetylase 2 (HDAC2) in NETs formation and its impact on antimicrobial and anti-inflammatory activities in sepsis. We employed flow cytometry, immunofluorescence and western blotting to assess NETs formation. The effects of HDAC2 on NETs and sepsis outcomes were investigated using an HDAC2 inhibitor and HDAC2 knockout mice in CLP-induced and LPS-induced sepsis models. Histone modifications in neutrophils were also analyzed to explore HDAC2's regulatory mechanism. HDAC2 was found to be highly expressed in patients and mice with sepsis. While HDAC2 knockout or inhibition reduced inflammation and improved organ function in non-infectious sepsis, it decreased survival in infectious sepsis. In addition, knockout or inhibition of HDAC2 significantly reduced the NETs formation, and impaired the antimicrobial activities against E. coli infection in mice. Mechanistically, HDAC2 indirectly promoted H3R17 citrullination to induce the NETs formation through down-regulating H3K18 acetylation and interactively inhibiting CARM1-mediated H3R17 methylation in neutrophils. Furthermore, a dual inhibition strategy targeting HDAC2 and CARM1 not only suppressed inflammation, prevented from multiple organ dysfunction, but also enhanced the antimicrobial activities, which finally improved survival rate of mice with sepsis induced by cecal ligation and puncture (CLP). Our findings reveal a novel role for HDAC2 in modulating anti-infectious immunity through NETs formation during sepsis. This study provides a potential therapeutic strategy for sepsis by enhancing both antimicrobial and anti-inflammatory responses, offering a promising approach to preserve organ function and improve survival.