长期核苷类似物（Nuc）治疗可以减少乙型肝炎病毒（HBV）相关肝硬化（HBV-LC）患者的肝细胞癌（HCC）发生。早期的小队列研究显示，停药和继续使用Nuc治疗的HBeAg阴性HBV-LC患者的5年HCC发生率相当。本研究旨在使用具有10年随访的大队列验证这些发现。从两个中心招募了494例停药组和593例继续治疗组的HBeAg阴性HBV-LC患者。利用性别、先前治疗历史、核苷类似物类型、年龄、转氨酶、血小板计数以及停药组治疗结束时（EOT）或继续治疗组治疗3年时的HBsAg水平的1:1倾向性评分匹配（PSM），比较了两组之间的HCC发生率、乙型肝炎表面抗原（HBsAg）消失率、肝相关死亡/移植率和总生存率。在中位随访时间为6.2（3.4-8.9）年的情况下，停药组的年HCC发生率和10年HCC发生率较低（分别为1.6% vs. 3.3%/年和10年 15.7% vs. 26.8%，Log-rank test, p<0.0001）。停药组的HBsAg每年下降量较大（-0.116 vs. -0.095 log10 IU/mL，p=0.0026）并且10年HBsAg消失率高于继续治疗组的7-8倍（22.7% vs. 3%，p<0.0001）。多变量Cox回归显示，停药治疗是HCC（调整风险比[aHR]：0.593）、肝相关死亡/移植（aHR：0.312）和总死亡（aHR：0.382）的独立保护因素。在HBeAg阴性HBV-LC中进行有限的核苷类似物治疗可以降低HCC发生率，增加HBsAg的消失率，并改善生存率。更大的HBsAg下降/消失可能反映了免疫增强，并有助于减少肝肿瘤的发生。版权所有 © 2023年美国肝病研究协会。

Long-term nucleos(t)ide analogue (Nuc) treatment can reduce hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-related cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in hepatitis B e antigen (HBeAg)-negative HBV-LC patients who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up.From two centers, 494 HBeAg-negative HBV-LC patients who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, hepatitis B surface antigen (HBsAg) loss, liver-related mortality/transplantation and overall survival rates were compared between two groups with 1:1 propensity score matching (PSM) of gender, prior treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end-of-therapy (EOT) in finite group or 3-year-on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/year and 10-year 15.7 vs. 26.8%, respectively; Log-rank test, p<0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log10 IU/mL, p=0.0026) and 7-8 times higher 10-year incidence of HBsAg loss (22.7 vs. 3%, p<0.0001). Multivariate Cox regression showed finite therapy an independent protective factor for HCC [adjusted hazard ratio(aHR): 0.593], liver-related mortality/transplantation (aHR: 0.312) and overall mortality (aHR: 0.382).Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.Copyright © 2023 American Association for the Study of Liver Diseases.