一种优化的干扰素间歇治疗模式有助于改善慢性乙型肝炎患

StephenW

一种优化的干扰素间歇治疗模式有助于改善慢性乙型肝炎患者的 HBsAg 消失
李明辉 1 2 , 思燮 3 , 毕晓月 1 , 孙芳芳 1 , 曾增 2 , 文登 1 , 蒋婷婷 1 , 林彦杰 2 , 刘洋 1 , 姚璐 1 , 张璐 1 , 卫毅 4 , 姚谢 1 2
隶属关系
隶属关系

    1
    【作者单位】： 首都医科大学北京地坛医院肝病二科;
    2
    【作者单位】： 北京大学地坛教学医院肝病二科;
    3
    清华大学北京清华长庚医院临床医学院肝胆胰中心肝病科
    4
    【作者单位】： 首都医科大学北京地坛医院妇产科;

    PMID：36110295 PMCID：PMC9468551 DOI：10.3389/fmicb.2022.960589

抽象的

背景：探讨间歇干扰素治疗模式对慢性乙型肝炎（CHB）患者乙型肝炎表面抗原（HBsAg）消失的影响。

方法：这是一项回顾性队列研究，研究对象为在初始治疗期间因 HBsAg 下降平台期而暂停聚乙二醇干扰素α (PEG-IFNα) 治疗并在间隔 3-6 个月后恢复干扰素治疗的 CHB 患者。患者在间隔期间接受恩替卡韦或替诺福韦治疗。在基线和初始干扰素治疗的随访期间每3个月进行一次乙型肝炎病毒（HBV）病毒学和血清学指标、临床生化指标和血常规检测。功能性治愈被分析为主要结果。

结果：共纳入304例间歇性PEG-IFNα治疗的患者，其中男性215例，女性89例，年龄37.97±8.53岁，乙型肝炎e抗原（HBeAg）阴性73例，HBeAg阳性231例。共有 59 名患者（19.41%）通过 PEG-IFNα 治疗的初始、间断和再治疗实现 HBsAg 消失，其中 43 名患者（14.14%）实现 HBsAg 血清学转换。对初始治疗的早期 HBsAg 反应与再治疗 12 周和 24 周时的 HBsAg 反应显着相关。间断期后，复治期早期HBsAg反应患者HBsAg消失的发生率为43.87%。再治疗期间的基线 HBsAg 和 12 周 HBsAg 反应比初始治疗 HBsAg 反应具有更高的预测价值。

结论：干扰素初始、间断、复治模式有助于提高慢性乙型肝炎患者HBsAg的消失率。

临床试验注册：[www.ClinicalTrials.gov]，标识符 [NCT04028856]。

关键词：乙肝；乙肝表面抗原；临床治愈；干扰素；间断治疗。

版权所有 © 2022 Li, Xie, Bi, Sun, Zeng, Deng, Jiang, Lin, Yang, Lu, Zhang, Yi and Xie。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。审稿人 BF 在审稿时向负责编辑声明了与几位作者 ZZ、YnL、ML 和 YX 的共同父母关系。

StephenW

An optimized mode of interferon intermittent therapy help improve HBsAg disappearance in chronic hepatitis B patients
Minghui Li  1   2 , Si Xie  3 , Xiaoyue Bi  1 , Fangfang Sun  1 , Zhan Zeng  2 , Wen Deng  1 , Tingting Jiang  1 , Yanjie Lin  2 , Liu Yang  1 , Yao Lu  1 , Lu Zhang  1 , Wei Yi  4 , Yao Xie  1   2
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    2
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.
    3
    Division of Hepatology, Hepato-Pancreato-Biliary Center, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
    4
    Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

    PMID: 36110295 PMCID: PMC9468551 DOI: 10.3389/fmicb.2022.960589

Abstract

Background: To investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients.

Methods: This is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3-6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome.

Results: A total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response.

Conclusion: The initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients.

Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT04028856].

Keywords: HBV; HBsAg; clinical cure; interferon; intermittent therapy.

Copyright © 2022 Li, Xie, Bi, Sun, Zeng, Deng, Jiang, Lin, Yang, Lu, Zhang, Yi and Xie.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, BF, declared a shared parent affiliation with several authors, ZZ, YnL, ML, and YX, to the handling editor at the time of review.

StephenW

https://www.frontiersin.org/arti ... icb.2022.960589/pdf

newchinabok

谢尧教授说要发一个论文就是这篇

newchinabok

今天仔细读了英文版，一次间歇治愈有数据，二次，三次间歇还可以继续探索提高治愈率，间隔三月，半年，一年哪个更优。我准备停八个月或一年，重走长征路，持续关注自己hbsag反弹情况

小牡丹

探讨降价和降低副作用才有意义。目前的干扰素治愈率与核苷酸没有多少区别。抗原很少的人迟早都能上岸，与目前的治疗方法关系不大。

newchinabok

小牡丹 发表于 2022-9-18 20:14
探讨降价和降低副作用才有意义。目前的干扰素治愈率与核苷酸没有多少区别。抗原很少的人迟早都能上岸，与目 ...

讨论那些，牧丹花都谢了

StephenW

小牡丹 发表于 2022-9-18 20:14
探讨降价和降低副作用才有意义。目前的干扰素治愈率与核苷酸没有多少区别。抗原很少的人迟早都能上岸，与目 ...

"探讨降价和降低副作用" - 我同意. 还应该剂量和持续时间.

https://www.mdpi.com/2076-393X/9/4/328/pdf
"在治疗性蛋白质中，应强调干扰素 (IFN) 的作用，因为
它们已上市 30 多年，对全球产生了相当大的影响
治疗性蛋白质市场 [3]。然而，正如最近 Timmerman [9] 在
干扰素轨迹的历史，从病毒干扰到 Hoffmann-La Roche
产品（Roferon A®, Hoffmann-La Roche, Basel, Switzerland），一系列障碍必须
被克服——即限制使用重组 DNA，——符合
商业伙伴的利益及其对专利保护的需求，同时解决
在该领域工作的学术研究人员对科学成果的渴望。干扰素销售
在 1980 年代和 2000 年代之间达到顶峰，因为它们被大量销售并归类为
“多种药物”，治疗作用范围不断扩大。
从 1986 年到 1992 年，短短六年时间，世界 IFN 市场增长了
约 7.4 亿美元 [10]。最近，全球 IFN 市场估值为
2019 年为 69 亿美元，预计到 2020 年将增长到 75 亿美元左右
由于对使用干扰素以及抗逆转录病毒和抗疟药的需求不断增加
治疗 SARS-CoV-2 病 (COVID-19) 患者的药物 [11]。此外，
这些预测得到了慢性病发病率增加的支持，例如
乙型肝炎、丙型肝炎和多发性硬化症，以及联合使用干扰素
自然疗法，越来越多地采用具有可能预防性的 IFN 生物仿制药
或对病毒大流行的治疗效果，新型药物递送的出现
系统，以及涉及干扰素的持续研发活动 [11]。由于它们的相关性，一些
干扰素产品目前处于不同的临床试验阶段。到 2021 年 1 月，172 人活跃
涉及应用基于治疗性干扰素的产品的临床试验在不同的
发展阶段：2个处于早期阶段1，50个处于第1阶段，70个处于第2阶段，28个处于第3阶段，
和 6 在临床试验的第 4 阶段 [12]。"
"Among therapeutic proteins, the role of interferons (IFN) should be underlined, as
they have been marketed for over 30 years with a considerable impact on the global
therapeutic proteins market [3 ]. However, as recently highlighted by Timmerman [ 9 ] on
the history of interferon’s trajectory, from the viral interference to the Hoffmann-La Roche
product (Roferon A®, Hoffmann-La Roche, Basel, Switzerland), a series of obstacles had to
be overcome-namely, restrictions to working with recombinant DNA, -to be in line with the
interests of commercial partners and their demands for patent protection while addressing
the desire by academic researchers working in the field for scientific outputs. IFN sales
peaked between the 1980s and 2000s, as they were abundantly marketed and classified as
“multiple drugs”, with an increasing range of therapeutic effects.
In a period of just six years, from 1986 to 1992, the world IFN market increased by
approximately $740 million [ 10]. More recently, the global IFN market was valued at
$6.9 billion in 2019, and it was estimated that it could grow to about $7.5 billion by 2020
due to an increasing demand for the use of IFNs along with antiretrovirals and antimalarial
drugs in the treatment of SARS-CoV-2 disease (COVID-19) patients [ 11]. Furthermore,
these projections are supported by the increasing incidence of chronic diseases, such as
hepatitis B, hepatitis C, and multiple sclerosis, coupled with the use of IFNs in combi-
natorial therapies, the increasing adoption of IFN biosimilars with possible prophylactic
or therapeutic effectiveness against virus pandemics, the advent of novel drug delivery
systems, and continuous R&D activities involving IFNs [ 11 ]. Due to their relevance, several
IFN products are currently in different stages of clinical trials. By January 2021, 172 active
clinical trials involving the application of therapeutic IFN-based products were at different
stages of development: 2 are in early phase 1, 50 in phase 1, 70 in phase 2, 28 in phase 3,
and 6 in phase 4 of clinical trials [12]."

newchinabok

StephenW 发表于 2022-9-18 21:54
"探讨降价和降低副作用" - 我同意. 还应该剂量和持续时间.

https://www.mdpi.com/2076-393X/9/4/328/pdf ...

慢慢去做梦，拉些战友一起做梦