HBsAg的成分可预测HBeAg阳性慢性乙型肝炎患者治疗期间HBsAg的

StephenW

Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B

    Maria Pfefferkorn
    Tina Schott
    Stephan Böhm
    Renate Heyne
    Thomas Berg
    Florian van Bömmel
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Published:September 12, 2020DOI:https://doi.org/10.1016/j.jhep.2020.08.039

Highlights

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    Ratios of large (L), medium (M) and small (S) HBsAg varied before and during antiviral treatment in patients achieving or not achieving HBsAg loss.
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    The proportion of MHBs is a suitable marker for early prediction of HBsAg loss.
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    Quantification of HBsAg proteins might be a novel tool to predict HBsAg loss early on treatment.
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    With this tool, treatment approaches may be individualized and HBsAg loss rates increased.

Background & Aims
During treatment of chronic HBV infections, loss or seroconversion of the HBV surface antigen (HBsAg) is considered a functional cure. HBsAg consists of the large (LHBs), middle (MHBs), and small surface protein (SHBs) and their relative proportions correlate strongly with disease stage. Our aim was to assess the association between HBsAg composition and functional cure during treatment.
Methods
A total of 83 patients were retrospectively analyzed. HBsAg loss was achieved by 17/64 patients during nucleos(t)ide analogue (NA) treatment and 3/19 patients following treatment with pegylated interferon-alfa2a (PEG-IFN) for 48 weeks. Sixty-three patients without HBsAg loss were matched as controls. LHBs, MHBs and SHBs were quantified in sera collected before and during treatment.
Results
Before treatment, median MHBs levels were significantly lower in patients with subsequent HBsAg loss than in those without ( p = 0.005). During treatment, MHBs and LHBs proportions showed a fast decline in patients with HBsAg loss, but not in patients with HBV e antigen seroconversion only or patients without serologic response. MHBs became undetectable by month 6 of NA treatment in all patients with HBsAg loss, which occurred on average 12.8 ± 8.7 (0–52) months before loss of total HBsAg. Receiver-operating characteristic analyses revealed that the proportion of MHBs was the best early predictor of HBsAg loss before NA treatment (AUC = 0.726, p = 0.019). In patients achieving HBsAg loss with PEG-IFN, the proportions of MHBs and LHBs showed similar kinetics.
Conclusion
Quantification of HBsAg proteins shows promise as a novel tool to predict early treatment response. These assessments may help optimize individual antiviral treatment, increasing the rates of functional cure in chronically HBV-infected patients.
Lay summary
The hepatitis B surface antigen (HBsAg) is a key serum marker for viral replication. Loss of HBsAg is considered stable remission, which can be achieved with antiviral treatments. We have investigated whether the ratios of the different components of HBsAg, namely the large (LHBs) and medium (MHBs) HBsAg during different treatments are associated with the occurrence of HBsAg loss. We found that LHBs and MHBs decrease earlier than total HBsAg before HBsAg loss and we propose LHBs and MHBs as promising novel biomarker candidates for predicting cure of HBV infection.

StephenW

HBsAg的成分可预测HBeAg阳性慢性乙型肝炎患者治疗期间HBsAg的流失

    玛丽亚·普费佛功（Maria Pfefferkorn）
    蒂娜·肖特（Tina Schott）
    斯蒂芬·伯姆
    Renate Heyne
    托马斯·伯格
    弗洛里安·范·博梅尔
    显示所有作者

发布时间：2020年9月12日DOI：https：//doi.org/10.1016/j.jhep.2020.08.039

强调

    •
    在达到或未达到HBsAg损失的患者中，抗病毒治疗前后大（L），中（M）和小（S）HBsAg的比例均发生变化。
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    MHBs的比例是早期预测HBsAg丢失的合适标记。
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    HBsAg蛋白的定量可能是一种在治疗早期预测HBsAg丢失的新颖工具。
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    使用该工具，治疗方法可以个性化，HBsAg丢失率增加。

背景与目标
在慢性HBV感染的治疗过程中，HBV表面抗原（HBsAg）的丧失或血清转化被认为是功能性治愈。 HBsAg由大（LHBs），中（MHBs）和小表面蛋白（SHBs）组成，它们的相对比例与疾病阶段密切相关。我们的目的是评估治疗过程中HBsAg成分与功能性治愈之间的关联。
方法
回顾性分析了83例患者。在核苷酸类似物（NA）治疗期间17/64例患者达到HBsAg丢失，在聚乙二醇干扰素-α2a（PEG-IFN）治疗48周后达到3/19例。将无HBsAg丢失的63例患者作为对照。在治疗前和治疗过程中，对收集的血清中的LHB，MHB和SHB进行定量。
结果
治疗前，继发HBsAg丢失的患者中MHBs水平显着低于无HBsAg的患者（p = 0.005）。在治疗过程中，HBsAg丢失患者的MHBs和LHBs比例迅速下降，而仅HBV e抗原血清转化或无血清反应的患者则没有下降。在所有HBsAg丢失的患者中，到NA治疗的第6个月都无法检测到MHBs，这些患者平均在总HBsAg丢失之前的12.8±8.7（0-52）个月内发生。接受者操作特征分析显示，在NA治疗之前，MHBs的比例是HBsAg丢失的最佳早期预测指标（AUC = 0.726，p = 0.019）。在通过PEG-IFN实现HBsAg丧失的患者中，MHBs和LHBs的比例显示出相似的动力学。
结论
HBsAg蛋白的定量显示有望作为预测早期治疗反应的新工具。这些评估可能有助于优化个体抗病毒治疗，提高慢性HBV感染患者的功能治愈率。
放置摘要
乙型肝炎表面抗原（HBsAg）是病毒复制的关键血清标志物。 HBsAg的丢失被认为是稳定的缓解，这可以通过抗病毒治疗来实现。我们调查了不同治疗期间HBsAg不同成分的比率，即大（LHBs）和中等（MHBs）HBsAg是否与HBsAg丢失的发生有关。我们发现LHBs和MHBs在HBsAg丧失之前比总HBsAg下降得更早，我们提出LHBs和MHBs是有希望的新型生物标志物候选物，可预测HBV感染的治愈。