摘要慢性乙型肝炎病毒（HBV）感染是病毒性肝炎、肝硬化和原发性肝细胞癌的主要致病原因，也是全球重大的公共卫生问题。随着慢性感染病程的进展，HBV DNA不断整合进入宿主DNA，并带来对宿主基因的整合插入突变。携带有HBV DNA整合的肝细胞具有增殖优势，在反复的慢性炎性坏死和代偿性再生过程中往往能够形成克隆性扩增，使突变随时间积累并最终导致肝细胞的恶性转化。尽管目前应用最为广泛的核苷（酸）类似物（NAs）能够有效抑制病毒复制，延缓慢性乙型肝炎患者的疾病进展并显著减少了终末期肝病的发生，但依然有很多患者进展成肝癌，甚至在乙型肝炎表面抗原清除的临床治愈的患者中，长期的肝癌发生依然存在，提示在既往治疗策略下NAs降低肝癌发生风险的作用有限。究其原因，可能与启动抗病毒治疗的时机选择有关，此时患者已经有众多的携带整合的细胞增生集落的积累，而NAs对整合的HBV DNA片段及其病毒蛋白如乙型肝炎表面抗原的表达并无治疗作用。据此建议应尽早启动抗病毒治疗，追求临床治愈，以最终降低慢性HBV感染者的肝癌发生风险。

abstractsChronic hepatitis B virus (HBV) infection is the main etiology of viral hepatitis, cirrhosis, and primary hepatocellular carcinoma and is also a major public health problem worldwide. With the progression of chronic infection, HBV DNA continuously integrates into host DNA and brings about integration and insertion mutations within host genes. In the process of repeated chronic inflammatory necrosis and compensatory regeneration, hepatocytes carrying HBV DNA integration have an advantage in proliferation and frequent clonal expansion formation that causes the accumulation of mutations over time and ultimately malignant transformation of hepatocytes. Although nucleos(t)ide analogs (NAs), currently the most widely used, can effectively inhibit viral replication, delay disease progression in patients with chronic hepatitis B, and significantly reduce the occurrence of end-stage liver disease, many patients still progress to liver cancer. Furthermore, even among clinically cured patients with hepatitis B surface antigen clearance, NAs have not significantly reduced the long-term occurrence of liver cancer, suggesting that their impact under previous treatment strategies for reducing the risk of liver cancer is limited. This could be due to antiviral treatment initiation at a time when patients already have numerous integrated cell proliferation colonies. Hence, NAs have not had any therapeutic impact on the expression of integrated HBV DNA fragments and viral proteins, such as hepatitis B surface antigen. In light of this, we suggest initiating antiviral treatment as early as possible to pursue clinical cure and ultimately reduce the risk of liver cancer in patients with chronic HBV infection.