早期再治疗停止后，严重肝炎发作中的强大抗病毒反应持续

StephenW

早期再治疗停止后，严重肝炎发作中的强大抗病毒反应持续存在并导致 HBsAg 消失：一项概念验证研究
张明玲 1 , 钱荣南 1 , 廖云凡 1
隶属关系
联系

    1
    台湾桃园长庚大学医学院长庚纪念医院肝脏研究室。

    PMID：35716249 DOI：10.1111/hepr.13804

抽象的

目的：乙型肝炎爆发已被解释为针对可能导致 HBV 自发下降/清除的乙型肝炎病毒 (HBV) 及其抗原的免疫反应的结果。据推测，抗病毒治疗可以阻止有效的免疫反应，从而导致病毒持续存在。进行了概念验证研究来调查这个问题。

方法：对 4 名 HBsAg 急剧下降的严重肝炎复发患者进行系列生化、定量乙型肝炎表面抗原 (HBsAg)、干扰素-γ (IFN-γ) 和肿瘤坏死因子-α (TNF-α) 检测抗病毒治疗 4 周内。

结果：发现所有患者中 TNF-α 和 IFN-γ 的升高与 HBV DNA 和 HBsAg 水平的升高平行。 2 名患者在 4 周内及早终止治疗期间和之后观察到更高水平的 TNF-α 和 IFN-γ 以及相对于 qHBsAg 的水平，随后 HBsAg 进一步下降至 <5 IU/mL，甚至 1 名患者 HBsAg 消失病人。在第 44 天停止治疗的患者随后 HBsAg 下降幅度很小，继续治疗的患者 qHBsAg 从最低点反弹 10 倍。这两名患者随后的 IFN-γ 和 TNF-α 活性很小。

结论：结果表明，HBsAg 急剧下降的重度肝炎复发患者可能具有清除病毒的强大免疫反应，而早期终止抗病毒治疗可能会使保护性免疫反应继续并加速 HBV 下降至 HBsAg 下降。本文受版权保护。版权所有。

关键词：HBeAg阴性慢性肝炎；宿主主导的耀斑；干扰素-γ (INF-γ)；核苷（酸）类似物；定量 HBsAg；肿瘤坏死因子-α (TNF-α)；以病毒为主的耀斑。

本文受版权保护。版权所有。

StephenW

Robust antiviral responses in severe hepatitis flare persist after early retreatment cessation and lead toward HBsAg loss: A proof-of-concept study
Ming-Ling Chang  1 , Rong-Nan Chien  1 , Yun-Fan Liaw  1
Affiliations
Affiliation

    1
    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine Taipei, Taoyuan, Taiwan.

    PMID: 35716249 DOI: 10.1111/hepr.13804

Abstract

Aim: Hepatitis B flare has been interpreted as result of immune response against upsurging hepatitis B virus (HBV) and its antigen(s) that may lead to HBV decline/clearance spontaneously. It has been speculated that antiviral therapy could halt the effective immune response with viral persistent as a consequence. A proof-of-concept study was conducted to investigate this issue.

Methods: Serial biochemical, quantitative hepatitis B surface antigen (HBsAg), interferon-γ (IFN-γ) and tumor-necrosis factor-α (TNF-α) assays were performed in 4 patients with severe hepatitis flare who had achieved precipitous HBsAg decline within 4 weeks of antiviral therapy.

Results: TNF-α and IFN-γ were found to be elevated in parallel to upsurging HBV DNA and HBsAg levels in all patients. Higher levels of TNF-α and IFN-γ and levels relative to qHBsAg were observed during and after early termination of therapy within 4 weeks in 2 patients and were followed by further HBsAg decline to <5 IU/mL and even achieved HBsAg loss in one patient. The patient who had stopped therapy on day 44 showed minimal HBsAg decline afterward and the patient who continued therapy showed a 10-fold rebound of qHBsAg from its nadir. The subsequent IFN-γ and TNF-α activity of these two patients was minimal.

Conclusions: The results suggest that patients with severe hepatitis flare who achieved precipitous HBsAg decline may have robust immune response to clear the virus, and early termination of antiviral therapy may allow the protective immune response to continue and accelerate HBV decline toward HBsAg loss. This article is protected by copyright. All rights reserved.

Keywords: HBeAg-negative chronic hepatitis; host-dominating flare; interferon-γ (INF-γ); nucleos(t)ide analogue; quantitative HBsAg; tumor necrosis factor-α (TNF-α); virus-dominating flare.

This article is protected by copyright. All rights reserved.