乙型肝炎表面抗原损失：太少，太晚和未来的挑战

StephenW

Hepatitis B Surface Antigen Loss: Too Little, Too Late and the Challenge for the Future
Geoffrey Dusheiko'Correspondence information about the author Geoffrey DusheikoEmail the author Geoffrey Dusheiko
Liver Unit, Kings College Hospital and University College London Medical School, London, UK
Bo Wang
Liver Unit, Kings College Hospital, London, UK
PlumX Metrics
DOI: https://doi.org/10.1053/j.gastro.2019.01.015 |

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See “Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: a systematic review and meta-analysis,” by Yeo YH, Ho HJ, Yang H-I, et al, on page 635.

Detectable hepatitis B surface antigen (HBsAg) is the serological hallmark of persistent hepatitis B virus (HBV) infection and disease. Loss of HBsAg signifies a favorable outcome of the natural history, particularly if HBsAg loss occurs before the accrual of significant liver disease. Loss of HBsAg has been defined, for reference, as a functional “cure.” However, HBsAg is infrequently cleared in those with chronic hepatitis B.

In the current issue of Gastroenterology, Yeo et al1 have performed a systematic review and meta-analysis of HBsAg clearance rates and predictors of clearance. Of 42,588 patients, 3194 cleared HBsAg. The pooled annual rate of HBsAg seroclearance was 1.02% (95% confidence interval, 0.79–1.27). Favorable factors for HBsAg loss included hepatitis B e antigen (HBeAg) negativity, a lower quantitative HBsAg level, and lower HBV DNA concentrations at baseline. Numerically, genotype A had the highest HBsAg seroclearance rates. No marked regional differences were noted, but seroclearance rates were numerically higher in community versus health service-based cohorts. Treatment had little effect, although higher HBsAg seroclearance rates were observed in interferon-treated patients than nucleos(t)ide analogue (NUC) recipients.

StephenW

乙型肝炎表面抗原损失：太少，太晚和未来的挑战
Geoffrey Dusheiko'关于作者的相关信息Geoffrey DusheikoEmail作者Geoffrey Dusheiko
英国伦敦国王学院医院和伦敦大学医学院肝脏科
王波
英国伦敦国王学院医院肝脏科
PlumX度量标准
DOI：https：//doi.org/10.1053/j.gastro.2019.01.015 |

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参见Yeo YH，Ho HJ，Yang H-I等人在第635页上的“与慢性HBV感染成人HBsAg血清清除率相关的因素：系统评价和荟萃分析”。

可检测的乙型肝炎表面抗原（HBsAg）是持续性乙型肝炎病毒（HBV）感染和疾病的血清学标志。 HBsAg的丢失意味着自然病史的有利结果，特别是如果HBsAg丢失发生在显着肝脏疾病的累积之前。作为参考，HBsAg的缺失已被定义为功能性“治愈”。然而，HBsAg在慢性乙型肝炎患者中很少被清除。

在当前的胃肠病学杂志中，Yeo等人对HBsAg清除率和清除预测因子进行了系统评价和荟萃分析。在42,588名患者中，3194人清除了HBsAg。汇总的HBsAg血清清除率为1.02％（95％置信区间，0.79-1.27）。 HBsAg丢失的有利因素包括乙型肝炎e抗原（HBeAg）阴性，HBsAg定量水平较低，基线时HBV DNA浓度较低。在数字上，基因型A具有最高的HBsAg血清清除率。没有发现明显的区域差异，但在社区与基于卫生服务的队列中，血清淋出率在数值上更高。尽管在干扰素治疗的患者中观察到的HBsAg血清清除率高于核苷（酸）类似物（NUC）受体，但治疗效果甚微。

StephenW

https://www.gastrojournal.org/ar ... aven_jbs_etoc_email

StephenW

Several potential strategies exist to achieve higher rates of HBsAg loss with treatment of a finite duration, which suggest several editorialized projections of where the field may go.

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    Covalently closed circular DNA is not eliminated by treatment with NUCs, which have less effect on HBV RNA and HBsAg, despite inhibiting HBV replication.
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    Novel capsid assembly modulators deepen inhibition of HBV replication by disrupting crucial early and late states of the HBV life cycle; these agents cause a decrease in HBV DNA and HBV RNA, but have a limited effect on HBsAg after 28 days and will require a longer duration of therapy to reduce HBsAg.
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    Sequential combinatorial therapy ideally should cause a precipitous decrease in HBsAg that, when followed by an immunomodulatory therapy, leads to sustained HBsAg loss.
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    Indeed, GalNac small interfering RNA knockdown in transgenic and transduced mice of HBsAg followed by an adjuvant therapeutic vaccine provides an elegantly choreographed proof of concept.25 These data require further clinical experimentation in humans with chronic hepatitis B.
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    Nucleic acid polymers, which block assembly and release of subviral particles, followed by pegylated interferon result in marked HBsAg reduction (and anti-HBs development), but require further validation and safety testing.26
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    Several immunomodulatory strategies including RIG-1 agonism or oral Toll-like receptor agonists or check point inhibition could trigger effective innate and adaptive immune responses after HBsAg reduction.
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    These strategies will need tailoring to the immunologic phenotype in patients with high and lower levels of HBV replication, to adjudge their effectiveness in different populations and at different stages of disease.

StephenW

有一些潜在的策略可以通过有限持续时间的治疗来实现更高的HBsAg丢失率，这表明了对该领域可能去向的几个编辑预测。

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    通过用NUC处理不能消除共价闭合的环状DNA，尽管抑制了HBV复制，但NUC对HBV RNA和HBsAg的影响较小。
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    新型衣壳组装调节剂通过破坏HBV生命周期的关键早期和晚期状态来加深对HBV复制的抑制作用;这些药物导致HBV DNA和HBV RNA降低，但28天后对HBsAg的影响有限，需要较长的治疗时间才能降低HBsAg。
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    顺序组合疗法理想情况下应引起HBsAg急剧下降，当接着进行免疫调节治疗时，会导致HBsAg持续丧失。
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    实际上，GalNac在HBsAg的转基因和转导小鼠中的小干扰RNA敲除随后是辅助治疗性疫苗提供了优雅精心设计的概念证明.25这些数据需要在患有慢性乙型肝炎的人中进行进一步的临床实验。
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    阻断亚病毒颗粒组装和释放的核酸聚合物，随后是聚乙二醇化干扰素，导致HBsAg明显减少（和抗HBs发展），但需要进一步验证和安全性测试。
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    几种免疫调节策略包括RIG-1激动剂或口服Toll样受体激动剂或检查点抑制可以在HBsAg减少后引发有效的先天性和适应性免疫应答。
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    这些策略需要针对具有高水平和低水平HBV复制的患者的免疫表型进行调整，以确定其在不同群体和疾病的不同阶段的有效性

sky8989

衣壳抑制剂加免疫药，乙肝治愈。但到现在，衣壳抑制剂都没还没确定能成功。还是寄希望于纳米机器人吧