Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.

慢性乙型肝炎病毒 (HBV) 感染目前无法治愈。使用有效且安全的核苷（酸）类似物 (NAs) 进行长期治疗可以通过深度抑制病毒来减少肝细胞癌 (HCC) 和肝硬化相关并发症。然而，无限期治疗提出了几个关键的利弊问题。由于乙型肝炎表面 (HBsAg) 的血清清除作为功能性治愈并不容易实现，因此包括连续 48 周聚乙二醇干扰素治疗在内的有限疗法可能提供机会，通过使耗尽的免疫细胞恢复活力来促进 HBsAg 血清清除。然而，停止 NA 的代价是病毒学复发的高发生率和丙氨酸氨基转移酶 (ALT) 水平的激增，这可能会增加不良结局的风险（例如，失代偿、纤维化进展、HCC、或肝脏相关死亡率）。到目前为止，停止 NA 治疗的 APASL 标准是检测不到 HBV DNA 水平且 ALT 正常；然而，这种停止治疗的标准与病毒学/临床复发的各种发生率有关，并且超过 40% 的 NA 止动器最终接受再治疗。非常密集的随访策略和通过不同生物标志物识别病毒学/临床复发的低风险患者是安全停止 NA 治疗的关键。最近的研究表明，在治疗结束时将 HBsAg 水平降低至 < 100-200 IU/mL 似乎是决定何时停止 NAs 治疗的有用标志物。此外，还审查了几种病毒和宿主因素在预测临床复发方面的潜在作用。最后，APASL 指南提出了停止 NA 的规则和后续的随访策略，以在停止 NA 后获得更好的预后。一般来说，对于已经停止治疗的 HBeAg 阳性和 HBeAg 阴性患者，这些测量应至少每 1-3 个月进行一次，直到 12 个月。