Hao Bingyan, Liu Yachong, Wang Bohan, Wu Haofeng, Chen Yan, Zhang Lei
Hepatic Surgery Center, Institute of Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Paediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Exp Hematol Oncol. 2025 Mar 26;14(1):44. doi: 10.1186/s40164-025-00642-7.
Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.
肝癌是全球第三大致死原因，乙型肝炎病毒（HBV）感染被确定为其发生发展的主要危险因素。HBV相关肝细胞癌（HCC）的发生归因于多种机制，如病毒触发的细胞毒性免疫反应诱导的慢性炎症和肝细胞再生、HBV DNA插入突变引起的癌基因异常激活以及病毒癌蛋白介导的表观遗传改变。HBV病毒的包膜蛋白，即乙型肝炎表面抗原（HBsAg），是HBsAg阳性个体发生HCC风险增加的关键指标。研究发现，HBsAg血清清除状态与接受肝切除术的HCC患者的复发有关。更多证据表明，HBsAg在肿瘤从起始到进展的整个发展过程中至关重要，并作为一种癌蛋白参与加速肿瘤进展。本综述全面分析了HBsAg在HCC起始和进展各阶段的广泛影响及内在机制。此外，还强调了HBsAg在HCC早期诊断和个性化治疗干预领域的重要性及潜在应用。本文深入阐述了HBsAg在HCC发生发展中的分子机制，有望为未来HCC的预防和管理制定更精准有效的策略。
