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Objective was to estimate the 5-year cumulative risk of HCC in patients with HBC by utilizing an artificial neural network (ANN). Methods: We conducted this study with 1589 patients hospitalized at Beijing Ditan Hospital of Capital Medical University and People's Liberation Army Fifth Medical Center. The training cohort consisted of 913 subjects from Beijing Ditan Hospital of Capital Medical University, while the validation cohort comprised 676 subjects from People's Liberation Army Fifth Medical Center. Through univariate analysis, we identified factors that independently influenced the occurrence of HCC, which were then used to develop the ANN model. To evaluate the ANN model, we assessed its predictive accuracy, discriminative ability, and clinical net benefit using metrics such as the area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curves. Results: In total, we included nine independent risk factors in the development of the ANN model. Remarkably, the AUC of the ANN model was 0.880, significantly outperforming the AUC values of other existing models including mPAGE-B (0.719) (95% CI 0.670– 0.768), PAGE-B (0. 710) (95% CI 0.660– 0.759), FIB-4 (0.693) (95% CI 0.640– 0.745), and Toronto hepatoma risk index (THRI) (0.705) (95% CI 0.654– 0.756) (p< 0.001 for all). The ANN model effectively stratified patients into low, medium, and high-risk groups based on their 5-year In the training cohort, the positive predictive value (PPV) for low-risk patients was 26.2% (95% CI 25.0– 27.4), and the negative predictive value (NPV) was 98.7% (95% CI 95.2– 99.7). For high-risk patients, the PPV was 54.7% (95% CI 48.6– 60.7), and the NPV was 91.6% (95% CI 89.4– 93.4). These findings were validated in the independent validation cohort. Conclusion: The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of the 5-year risk of HCC in patients with HBC. [ABSTRACT FROM AUTHOR]

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOS hi ) and low-ratio (PD-1/ICOS lo ) groups according to ratio median. Compared with PD-1/ICOS lo patients, the PD-1/ICOS hi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOS hi patients exhibited a higher proportion of tissue-resident memory T (T RM ) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOS lo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background and Aim: A high aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is associated with liver injury in liver disease; however, no data exist regarding its relationship with 90-day prognosis in patients with acute exacerbation of chronic liver disease., Methods: In this study, 3,758 participants (955 with advanced fibrosis and 2,803 with cirrhosis) from the CATCH-LIFE cohort in China were included. The relationships between different AST/ALT ratios and the risk of adverse 90-day outcomes (death or liver transplantation) were determined in patients with cirrhosis or hepatitis B virus (HBV)-associated advanced fibrosis, respectively., Results: In the patients with HBV-associated advanced fibrosis, the risk of 90-day adverse outcomes increased with AST/ALT ratio; after adjusting for all confounding factors, the risk of adverse 90-day outcomes was the highest when AST/ALT ratio was more than 1.08 (OR = 6.91 [95% CI = 1.789-26.721], p  = 0.005), and the AST/ALT ratio of >1.9 accelerated the development of adverse outcomes. In patients with cirrhosis, an AST/ALT ratio > 1.38 increased the risk of adverse 90-day outcomes in all univariables (OR = 1.551 [95% CI = 1.216-1.983], p  < 0.001) and multivariable-adjusted analyses (OR = 1.847 [95% CI = 1.361-2.514], p  < 0.001), and an elevated AST/ALT ratio (<2.65) accelerated the incidence of 90-day adverse outcomes. An AST/ALT ratio of >1.38 corresponded with a more than 20% incidence of adverse outcomes in patients with cirrhosis., Conclusion: The AST/ALT ratio is an independent risk factor for adverse 90-day outcomes in patients with cirrhosis and HBV-associated advanced fibrosis. The cutoff values of the AST/ALT ratio could help clinicians monitor the condition of patients when making clinical decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Deng, Zheng, Huang, Chen, Meng, Gao, Qian, Liu, Lu, Shi, Shang, Yan, Zheng, Shen, Qiao, Zhang and Wang.)