核潮类似物撤除后 HBsAg 消失的概率取决于 HBV 基因型和病毒

StephenW

核潮类似物撤除后 HBsAg 消失的概率取决于 HBV 基因型和病毒抗原水平

    米兰 J. Sonneveld †
    赵少明†
    俊勇公园
    陈建红‡
    本杰明·马苏米‡
    对于 CREATE 研究组
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开放存取发布时间：2022 年 1 月 26 日 DOI：https://doi.org/10.1016/j.jhep.2022.01.007
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强调

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    少数慢性乙型肝炎患者在停止抗病毒治疗后可能达到 HBsAg 清除。
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    在这项包含 1,216 名患者的多中心研究中，非亚洲种族与 HBsAg 消失的可能性最高有关。
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    在亚洲患者中，基因型 C 与更高的 HBsAg 消失机会相关。
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    低 HBsAg 水平 (<100 IU/ml) 和无法检测到的 HBcrAg 水平与 HBsAg 消失的机会较高有关。

背景与目标
核（s）潮类似物（NUC）的退出可能导致部分患者的 HBsAg 清除。然而，NUC 撤除后 HBsAg 消失的预测因子仍然不明确。
方法
我们在一个全球队列中研究了 HBsAg 消失的预测因素，这些患者是停止长期 NUC 治疗的 HBV DNA 检测不到的 HBeAg 阴性患者。治疗停止后需要再治疗的患者被认为是无反应者。
结果
我们招募了 1,216 名患者（991 名有基因型数据）； 98 人（8.1%）实现了 HBsAg 消失。非亚洲患者的 HBsAg 消失概率更高（调整后的风险比 [aHR] 8.26，p <0.001），以及 HBsAg 较低（aHR 0.243，p <0.001）和 HBV 核心相关抗原（HBcrAg）的患者（ aHR 0.718, p = 0.001) 水平。结合 HBsAg（<10、10-100 或 >100 IU/ml）和 HBcrAg（<2log vs. ≥2 log）水平可改善对 HBsAg 消失的预测，在 HBsAg >100 IU/ml 且可检测到的患者中观察到的比率极低HBcrAg。 HBsAg 消失率也因 HBV 基因型而异。基因型 A 和 D 的发生率最高，且基因型 E 的 HBV 患者均未出现 HBsAg 下降（基因型的总体比较 p <0.001；基因型 A/D 与基因型 B/C 的 p <0.001）。在亚洲患者中，与基因型 B 相比，HBV 基因型 C 与更高的 HBsAg 消失概率独立相关（aHR 2.494；95% CI 1.490–4.174，p = 0.001）。
结论
NUC 停止后 HBsAg 消失的可能性因患者种族、HBV 基因型和治疗结束病毒抗原水平而异。 HBsAg 低（<100 IU/ml）和/或检测不到 HBcrAg 水平的患者，尤其是非亚洲人或感染 HBV 基因 C 型的患者，似乎是停止治疗的最佳人选。
总结
部分患者在停用核（S）潮类似物治疗后可能实现乙型肝炎表面抗原（HBsAg）的清除——即所谓的功能性治愈。在这项针对 1,216 名停止抗病毒治疗的患者的多中心研究中，我们确定了非亚洲种族、HBV 基因 C 型以及乙型肝炎表面抗原和乙型肝炎核心相关抗原水平低是与 HBsAg 消失机会增加相关的因素。

StephenW

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels

    Milan J. Sonneveld †
    Shao-Ming Chiu †
    Jun Yong Park
    Chien-Hung Chen ‡
    Benjamin Maasoumy ‡
    for theCREATE study group
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Open AccessPublished:January 26, 2022DOI:https://doi.org/10.1016/j.jhep.2022.01.007
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Highlights

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    A minority of patients with chronic hepatitis B may achieve HBsAg clearance after withdrawal of antiviral therapy.
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    In this multicenter study comprising 1,216 patients, non-Asian ethnicity was associated with the highest chance of HBsAg loss.
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    Among Asian patients, genotype C was associated with a higher chance of HBsAg loss.
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    Low HBsAg levels (<100 IU/ml) and undetectable HBcrAg levels were associated with a higher chance of HBsAg loss.

Background & Aims
Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined.
Methods
We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders.
Results
We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p <0.001), and in patients with lower HBsAg (aHR 0.243, p <0.001) and HBV core-related antigen (HBcrAg) (aHR 0.718, p = 0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/ml) and HBcrAg (<2log vs. ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490–4.174, p = 0.001).
Conclusions
The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal.
Lay summary
A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) – so-called functional cure – after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss.

StephenW

https://www.journal-of-hepatolog ... 8278(22)00020-4/pdf