Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, China.
J Viral Hepat. 2021 Aug;28(8):1121-1129. doi: 10.1111/jvh.13526. Epub 2021 May 3.
The outcome of nucleos(t)ide analogues (NAs) discontinuation and retreatment is still uncertain. We evaluated hepatitis B surface antigen (HBsAg) kinetics after NAs discontinuation and during retreatment due to off-treatment clinical relapse among non-cirrhotic HBeAg-positive CHB patients. Four groups were studied: 129 HBeAg-positive patients from a prospective cohort who stopped NAs therapy after achieving sustained response (Group A), 39 patients who received retreatment after off-treatment clinical relapse in the discontinuation group (Group B), 214 patients who maintained treatment after achieving sustained response (Group C) and 291 patients who firstly initiated antiviral treatment (Group D). During a 5-year follow-up, the cumulative incidence of HBsAg loss was significantly higher in Group A than Group C (22.3% vs. 1.6%, p < .001). The quantitative HBsAg (qHBsAg) level at enrolment and NAs discontinuation were independently associated with HBsAg loss. Additionally, patients in Group B showed significantly greater HBsAg loss than those in the Groups C and D, with 5-year cumulative incidences of 9.0%, 1.6% (p = .040) and 0.6% (p < .001), respectively. Moreover, patients in the Group B exhibited better virologic response (100% vs. 98.8%, p < .001) and HBeAg seroconversion (92.6% vs. 69.8%, p < .001) than those in Group D at year 5. Propensity score-matched analysis also showed the similar trend of HBsAg decline. NAs discontinuation with or without subsequent retreatment resulted in a more profound reduction of HBsAg in non-cirrhotic HBeAg-positive patients, suggesting that discontinuation may be a potential cure strategy for those with sustained virological suppression.
核苷（酸）类似物（NAs）停药和再治疗的结果仍然不确定。我们评估了非肝硬化 HBeAg 阳性 CHB 患者因停药后临床复发而停止 NAs 治疗后和再治疗期间的乙型肝炎表面抗原（HBsAg）动力学。研究了 4 组患者：129 名来自前瞻性队列的 HBeAg 阳性患者，他们在获得持续应答后停止 NAs 治疗（A 组），39 名在停药组临床复发后接受再治疗的患者（B 组），214 名在获得持续应答后维持治疗的患者（C 组）和 291 名首次开始抗病毒治疗的患者（D 组）。在 5 年的随访中，A 组的 HBsAg 丢失累积发生率明显高于 C 组（22.3%比 1.6%，p<0.001）。基线时的 HBsAg 定量（qHBsAg）水平和 NAs 停药与 HBsAg 丢失独立相关。此外，B 组患者的 HBsAg 丢失明显大于 C 组和 D 组，5 年累积发生率分别为 9.0%、1.6%（p=0.040）和 0.6%（p<0.001）。此外，B 组患者在第 5 年时表现出更好的病毒学应答（100%比 98.8%，p<0.001）和 HBeAg 血清学转换（92.6%比 69.8%，p<0.001），而 D 组患者则无应答。倾向评分匹配分析也显示出 HBsAg 下降的类似趋势。对于非肝硬化 HBeAg 阳性患者，无论是否随后进行再治疗，停止 NAs 治疗都会导致 HBsAg 更明显的降低，提示停药可能是那些持续病毒抑制患者的潜在治愈策略。
