Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Gut. 2020 Dec;69(12):2214-2222. doi: 10.1136/gutjnl-2019-320015. Epub 2020 Mar 24.
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.
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).
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).
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.
在乙型肝炎表面抗原（HBsAg）清除后已停止核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者中，尚未对临床结局进行直接比较。本研究旨在探讨在 NAs 诱导的 HBV 表面抗原（HBsAg）清除后，停止 NAs 治疗是否与继续 NAs 治疗一样安全。
本多中心研究纳入了韩国 16 家医院的 276 例达到 NAs 诱导 HBsAg 清除的患者：131 例（47.5%）在 HBsAg 清除后 6 个月内停止 NAs 治疗（NA 停药组），145 例（52.5%）继续 NAs 治疗（NA 继续组）。主要终点是 HBsAg 逆转，次要终点包括血清 HBV DNA 再次检测和肝细胞癌（HCC）的发生。
在随访期间（中位数=26.9 个月，IQR=12.2-49.2 个月），10 例患者（3.6%）出现 HBsAg 逆转，6 例（2.2%）出现 HBV DNA 再次检测，8 例（2.9%）发生 HCC。与 NA 继续组相比，单变量（HR=0.45，95%CI=0.12 至 1.76，对数秩检验 p=0.24）和多变量分析（调整 HR=0.65，95%CI=0.16 至 2.59，p=0.54）均显示 NA 停药与 HBsAg 逆转无关。NA 停药组 1、3 和 5 年时 HBsAg 逆转的累积概率分别为 0.8%、2.3%和 5.0%，NA 继续组分别为 1.5%、6.3%和 8.4%。NA 停药与 HBV 再检测（HR=0.83，95%CI=0.16 至 4.16，对数秩检验 p=0.82）或 HCC 发展（HR=0.53，95%CI=0.12 至 2.23，对数秩检验 p=0.38）的风险增加无关。
与继续 NAs 治疗相比，在达到 NAs 诱导 HBsAg 清除的患者中，停止 NAs 治疗与 HBsAg 逆转、血清 HBV DNA 再次检测或 HCC 发展的风险增加无关。
