Objective Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study. Designs This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance: 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC). Results During follow-up (median=26.9 months, IQR=12.2–49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38). Conclusion The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA.

中文翻译：

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停止使用核苷（酸）类似物与抗病毒诱导的 HBsAg 血清学清除后 HBsAg 血清学逆转的更高风险无关：一项全国性多中心研究

目的 尚未在实现 HBsAg 血清学清除的慢性乙型肝炎患者中直接比较核苷（酸）类似物（NA）停用与 NA 继续之间的临床结果。在本研究中调查了在 NA 诱导的 HBV 表面抗原（HBsAg）血清清除后，停止 NA 是否与继续 NA 一样安全。设计 这项多中心研究包括来自韩国 16 家医院的 276 名患者获得 NA 诱导的 HBsAg 血清清除：131 名（47.5%）在 HBsAg 血清清除后 6 个月内停止 NA 治疗（NA 终止组）和 145 名（52.5%）继续 NA 治疗（NA）续组）。主要终点是 HBsAg 逆转，次要终点包括血清 HBV DNA 重新检测和肝细胞癌 (HCC) 的发展。结果 随访期间（中位数 = 26. 9 个月，IQR=12.2-49.2 个月），10 名患者 (3.6%) 出现 HBsAg 逆转，6 名 (2.2%) 显示 HBV DNA 重新检测，8 名 (2.9%) 发展为 HCC。与继续使用 NA 相比，在单变量（HR=0.45，95% CI=0.12 至 1.76，对数秩 p=0.24）和多变量分析（调整后的 HR=0.65，95% CI=0.16）中，停止 NA 与 HBsAg 逆转无关到 2.59，p=0.54）。NA 停药组 1、3 和 5 年 HBsAg 逆转的累积概率分别为 0.8%、2.3% 和 5.0%，NA 继续治疗组分别为 1.5%、6.3% 和 8.4%。NA 停用与 HBV 再检出（HR=0.83，95% CI=0.16 至 4.16，log-rank p=0.82）或 HCC 发展（HR=0.53，95% CI=0.12 至 2.23，log-等级 p=0.38）。