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慢性乙型肝炎患者如果没有得到及时有效的抗病毒治疗,最终都将发展为肝硬化和/或肝细胞癌(HCC)。接受核苷(酸)类似物(NAs)治疗可有效抑制乙型肝炎病毒(HBV)复制,改善肝组织炎症和纤维化,阻止或延缓疾病进展,大大降低HBV相关HCC发生。然而在临床上常常可以发现,一些长期口服NAs治疗的患者,尽管HBV得到了有效抑制,仍然可以发生HCC,这种现象引起了广泛的关注和讨论。现将围绕NAs有效抑制HBV复制的同时,可以明显降低HCC发生,还是仍然可以发生HCC?以及NAs治疗后发生HCC可能的原因,包括药物的种类、治疗时机、病毒学不完全应答等方面进行讨论,帮助临床医生更加精准地实施抗病毒治疗,进一步降低HBV相关HCC。“,”Patients with chronic hepatitis B (CHB) who cannot receive effective antiviral therapy timely will eventually develop liver cirrhosis and/or hepatocellular carcinoma (HCC). Therefore, receiving nucleos(t)ide analogues (NAs) therapy can effectively inhibit hepatitis B virus (HBV) replication, improve liver tissue inflammation and fibrosis, prevent or delay the disease progression, and greatly reduce the occurrence of HBV-related HCC. However, it is often found in clinical practice that some patients treated with long-term NAs therapy can still develop HCC despite the effective inhibition of HBV replication. This phenomenon has attracted widespread concern and discussion. In this article, we focus on whether NAs can significantly reduce the occurrence of HCC while effectively inhibiting HBV replication, or HCC can still occur. Additionally, discuss the possible causes of HCC after NAs therapy, including the types of drugs, treatment timing, incomplete response, etc., in order to help clinicians implement antiviral treatment more accurately, and further reduce HBV-related HCC.