Lin Anqi, Xiong Minying, Tang Bufu, Jiang Aimin, Shen Junyi, Liu Zaoqu, Cheng Quan, Zhang Jian, Luo Peng
Jiangnan University Smart Healthcare Joint Laboratory, Donghai County People's Hospital (Kangda College of Nanjing Medical University), Lianyungang, 222000, Jiangsu Province, China.
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Hepatol Int. 2025 Jul 1. doi: 10.1007/s12072-025-10838-y.
Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent malignant neoplasm globally and represents the third-leading cause of cancer-associated mortality worldwide. Epidemiological data indicate that 80-90% of HCC cases demonstrate documented progression from hepatic fibrosis or cirrhosis. This fibrotic-carcinogenic continuum represents a complex multistep pathological cascade, with mechanistic insights being progressively revealed through contemporary investigations.
This review systematically elucidates the mechanistic contributions of dysregulated signaling pathways and immune microenvironmental remodeling during hepatic fibrocarcinogenesis.
A systematic online screening protocol was implemented across multiple biomedical databases to curate relevant studies elucidating mechanisms underlying fibrosis-driven hepatocarcinogenesis.
This work conducts a comprehensive pathophysiological analysis of hepatic fibrosis-HCC transition, including dysregulated cytokine networks, dynamic extracellular matrix (ECM) remodeling, epigenetic dysregulation, immune landscape reprogramming, persistent oxidative stress, and acquired mitochondrial dysfunction. The analysis comprehensively evaluates widely utilized experimental models in fibrotic liver carcinogenesis research, while critically assessing emerging biomarkers and mechanism-based therapeutic targets.
This synthesis lays conceptual foundations for advancing translational research on biomarker discovery and precision therapeutics, while offering substantive guidance for developing mechanistically informed strategies to optimize clinical outcomes in hepatic fibrosis and HCC management.
肝细胞癌（HCC）是全球第六大常见恶性肿瘤，也是全球癌症相关死亡的第三大原因。流行病学数据表明，80-90%的HCC病例显示有从肝纤维化或肝硬化发展而来的记录。这种纤维化-致癌连续体代表了一个复杂的多步骤病理级联反应，通过当代研究，其机制见解正逐渐被揭示。
本综述系统地阐明了肝纤维致癌过程中信号通路失调和免疫微环境重塑的机制作用。
在多个生物医学数据库中实施了系统的在线筛选方案，以整理阐明纤维化驱动肝癌发生机制的相关研究。
本研究对肝纤维化向HCC转变进行了全面的病理生理分析，包括细胞因子网络失调、动态细胞外基质（ECM）重塑、表观遗传失调、免疫格局重编程、持续氧化应激和获得性线粒体功能障碍。该分析全面评估了在纤维化肝癌发生研究中广泛使用的实验模型，同时严格评估了新兴的生物标志物和基于机制的治疗靶点。
本综述为推进生物标志物发现和精准治疗的转化研究奠定了概念基础，同时为制定基于机制的策略以优化肝纤维化和HCC管理的临床结果提供了实质性指导。
