未治疗和核苷（酸）类似物治疗的患者中乙型肝炎表面抗原

antiHBVren

Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients

Terry Cheuk-Fung Yip†, Grace Lai-Hung Wong†, Vincent Wai-Sun Wong, Yee-Kit Tse, Grace Chung-Yan Lui, Kelvin Long-Yan Lam, Henry Lik-Yuen Chan'Correspondence information about the author Henry Lik-Yuen ChanEmail the author Henry Lik-Yuen Chan
†Contributed equally to this work.
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Highlights
•Seroclearance of HBsAg is regarded as functional cure of chronic hepatitis B.
•Nucleos(t)ide analogues (NA)-induced HBsAg loss is as durable as spontaneous one.
•Presence of anti-HBs is not essential for maintaining HBsAg seroclearance after NA.
•No patients who had consolidation therapy >12 months developed HBsAg seroreversion.
Background & Aims
It is uncertain if nucleos(t)ide analogue (NA)-induced hepatitis B surface antigen (HBsAg) seroclearance is durable. We investigated the impact of hepatitis B surface antibody (anti-HBs) and duration of consolidation antiviral therapy on the durability of HBsAg seroclearance.

Methods
A territory-wide cohort study was conducted using data from the Hospital Authority, Hong Kong. We identified all subjects with positive HBsAg between January 1, 2000 and August 31, 2016. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was confirmed HBsAg seroclearance, defined least two negative HBsAg test results, with the last HBsAg test being negative in patients with chronic hepatitis B (CHB).

Results
A total of 4,080 CHB patients were included for analysis. In patients with spontaneous HBsAg seroclearance (n = 3,563), 1,771 patients (49.7%) had confirmed HBsAg seroclearance and 75 patients (2.1%) had HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n = 475), 320 patients (67.4%) had confirmed HBsAg seroclearance and 14 patients (2.9%) had HBsAg seroreversion. The five-year cumulative probability of confirmed HBsAg seroclearance was comparable in patients with spontaneous and NA-induced HBsAg seroclearance (88.1% vs. 92.2%; Log-rank test, p = 0.964); it was also similar in patients with or without anti-HBs in NA-treated patients (95.4% vs. 95.5%, Log-rank test, p = 0.602). HBsAg seroreversion was only observed in 3 (2.0%) patients who had received consolidation therapy for 6–12 months and none of those who had received it for ≥12 months.

Conclusions
NA-induced HBsAg seroclearance is as durable as spontaneous HBsAg seroclearance. NA-treated patients may not need to have positive anti-HBs before stopping treatment. Longer consolidation NA treatment may result in more durable HBsAg seroclearance.

Lay summary
We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance.

antiHBVren

未治疗和核苷（酸）类似物治疗的患者中乙型肝炎表面抗原血清清除的耐久性

强调
•乙肝表面抗原被认为是慢性乙型肝炎的功能性治愈
•核苷（酸）类似物（NA）诱导的HBsAg消失与自发性一样持久。
•抗-HBs的存在对于NA后维持HBsAg血清学清除不是必需的。
•没有巩固治疗> 12个月的患者发生HBsAg血清学转换。
背景和目的
核苷（酸）类似物（NA）诱导的乙肝表面抗原（HBsAg）血清学清除是否耐久是不确定的。我们调查了乙型肝炎表面抗体（抗-HBs）和巩固抗病毒治疗持续时间对HBsAg血清学清除的耐受性的影响。

方法
使用香港医院管理局的资料进行全港队列研究。我们在2000年1月1日至2016年8月31日期间确定了所有HBsAg阳性的受试者。检索了NA使用，肝生化，系列HBsAg和抗-HBs结果。主要终点证实为HBsAg血清学清除，确定至少两项HBsAg阴性检测结果，最后一项HBsAg检测在慢性乙型肝炎（CHB）患者中为阴性。

结果
共纳入4,080名CHB患者进行分析。在自发性HBsAg血清学清除（n = 3,563）的患者中，1771例（49.7％）确诊为HBsAg血清学清除，75例（2.1％）患者为HBsAg血清学转换。在NA诱导的HBsAg血清学清除（n = 475）中，320例（67.4％）确诊为HBsAg血清学清除，14例（2.9％）为HBsAg血清学转换。自发性和NA诱导的HBsAg血清学清除（88.1％比92.2％; Log-rank检验，p = 0.964）的患者确诊的HBsAg血清学清除的5年累积概率相当。在NA治疗的患者中有或没有抗-HBs的患者中也是相似的（95.4％比95.5％，Log-rank检验，p = 0.602）。仅有3例（2.0％）巩固治疗6-12个月的患者接受了HBsAg血清学转换，而且接受了12个月以上的患者也没有。

结论
NA诱导的HBsAg血清清除与自发性HBsAg血清清除一样持久。在停止治疗之前，NA治疗的患者可能不需要具有阳性的抗-HBs。更长时间的巩固NA治疗可能导致更持久的HBsAg血清学清除。

总结
我们调查了4,080名乙型肝炎表面抗原（HBsAg）血清学清除的患者。 HBsAg血清学转换发生在2.1％的自发性患者和2.9％的核苷（酸）类似物诱导的HBsAg血清学清除。