乙型肝炎e抗原阴性慢性乙型肝炎中核苷酸（t）类似物治疗停

StephenW

Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen–negative chronic hepatitis B
Wen‐Juei Jeng
Yi‐Cheng Chen
Rong‐Nan Chien
I‐Shyan Sheen
Yun‐Fan Liaw
First published: 06 November 2017
https://doi.org/10.1002/hep.29640
Cited by: 3

Potential conflict of interest: Nothing to report.

Supported by the Chang Gung Medical Research Fund (CMRPG1G0061, CMRPG3A0901‐3); the National Science Council, Taiwan (MOST105‐2628‐B‐182‐011‐MY3); and the Prosperous Foundation, Taiwan.

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Abstract

Hepatitis B surface antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e antigen–negative patients. A large study was conducted to investigate this issue in more detail. Of the 1,075 hepatitis B e antigen–negative patients treated with Nuc for a median of 156 (61‐430) weeks, 5 showed HBsAg seroclearance during treatment at an estimated annual incidence of 0.15%. Of the patients who remained HBsAg‐seropositive, 691 (52.3 years old, 86% male, 44.6% cirrhosis) had stopped Nuc therapy by the Asian‐Pacific Association for the Study of the Liver stopping rule and then were prospectively followed up. Baseline and on‐treatment clinical and viral features, treatment duration, consolidation duration, time to undetectable hepatitis B virus DNA, time to normal alanine aminotransferase, end‐of‐treatment HBsAg, and HBsAg log reduction were compared between patients with and without HBsAg seroclearance after end of treatment. During a median off‐therapy follow‐up period of 155 (2‐614) weeks, HBsAg seroclearance was confirmed in 42 patients. The 6‐year cumulative incidence was 13% with an estimated annual incidence of 1.78%. Cox regression analysis showed that shorter time to undetectable hepatitis B virus DNA (<12 weeks), greater HBsAg reduction during therapy (>1 log10), lower end‐of‐treatment HBsAg level (<100 IU/mL), patients with sustained response, and relapsers not retreated were factors for off‐therapy HBsAg seroclearance. Conclusion: The incidence of HBsAg seroclearance after stopping Nuc was much higher than that during therapy and highest in patients without virologic and clinical relapse; patients with clinical relapse who remained untreated had a 7.34 times higher incidence of HBsAg clearance than those who received retreatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. (Hepatology 2017).

StephenW

乙型肝炎e抗原阴性慢性乙型肝炎中核苷酸（t）类似物治疗停止后乙型肝炎表面抗原血清清除的发生率和预测因素
Jeng-Juei Jeng
陈义成
Rong-Nan Chien
I-Shyan Sheen
阎凡范
首次发布：2017年11月6日
https://doi.org/10.1002/hep.29640
引用次数：3

潜在的利益冲突：无需报告。

长庚医学研究基金（CMRPG1G0061，CMRPG3A0901-3）资助;台湾国家科学委员会（MOST105-2628-B-182-011-MY3）;和台湾的繁荣基金会。

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在核苷（酸）类似物（Nuc）治疗期间，乙型肝炎表面抗原（HBsAg）丢失是罕见的事件。有限的数据表明停止Nuc治疗可能会增加乙型肝炎e抗原阴性患者的HBsAg丢失率。进行了一项大型研究，以更详细地研究这个问题。在用Nuc治疗中位数为156（61-430）周的1,075名乙型肝炎e抗原阴性患者中，5名在治疗期间显示HBsAg血清清除，估计年发病率为0.15％。在保持HBsAg血清反应阳性的患者中，691名（52.3岁，86％男性，44.6％肝硬化）已经停止了亚太治疗肝停止治疗协会的Nuc治疗，然后进行了前瞻性随访。比较有和没有HBsAg血清清除的患者的基线和治疗临床和病毒特征，治疗持续时间，巩固持续时间，无法检测到的乙型肝炎病毒DNA的时间，正常丙氨酸氨基转移酶的时间，治疗结束时HBsAg和HBsAg对数减少治疗结束后。在155（2-614）周的中位疗效随访期间，42例患者确诊为HBsAg血清清除。 6年累积发病率为13％，估计年发病率为1.78％。 Cox回归分析显示，检测不到乙型肝炎病毒DNA的时间较短（<12周），治疗期间HBsAg降低幅度较大（> 1 log10），治疗结束时HBsAg水平较低（<100 IU / mL），持续应答持续时间较长的患者和未复发的复发者是治疗前HBsAg血清清除的因素。结论：停用Nuc后HBsAg血清清除率明显高于治疗期间，未发生病毒学和临床复发的患者最高;临床复发但仍未接受治疗的患者HBsAg清除率比接受再治疗的患者高7.34倍，这表明短暂的未经治疗的临床复发可能会对功能性治愈产生足够的免疫控制。 （Hepatology 2017）。