在長期恩替卡韋治療的 HBeAg 陽性慢性乙型肝炎患者中加用或

StephenW

在長期恩替卡韋治療的 HBeAg 陽性慢性乙型肝炎患者中加用或改用聚乙二醇干擾素 α-2b 的療效和安全性：一項多中心隨機對照試驗
胡乾坤 1 , 荀奇 1 , 於一琪 2 , 高月秋 3 , 張欣欣 4 , 王倩倩 1 , 張雪雲 2 , 卓雲輝 3 , 景麗 4 , 張繼明 2 , 梁晨 1 , 黃玉賢 1 2
隸屬關係
隸屬關係

    1
    復旦大學上海市公共衛生臨床中心肝病科，上海，中國。
    2
    復旦大學華山醫院國家傳染病醫學中心傳染病與生物安全應急響應上海市重點實驗室傳染病科，上海，中國。
    3
    【作者單位】： 上海中醫藥大學附屬曙光醫院肝病科;
    4
    【作者單位】： 上海交通大學醫學院附屬瑞金醫院感染科;

    PMID: 36128636 DOI: 10.1111/apt.17222

抽象的

背景與目的：添加或改用聚乙二醇干擾素 (PEG-IFN) 治療的策略提高了患有慢性乙型肝炎 (CHB) 患者的核苷（酸）類似物的血清學反應率。然而，仍然缺乏關於哪種組合策略更有效的可靠數據。

方法：在這項多中心、平行、開放標籤、隨機、對照試驗中，HBeAg 陽性 CHB 患者接受恩替卡韋 (ETV) 治療≥2 年，乙型肝炎表面抗原 (HBsAg) <3000 IU/ml，HBeAg <200S/CO和 HBV DNA <50 IU/ml 以 1:1:1 的比例隨機分配，以添加 PEG-IFN（添加）、切換到 PEG-IFN（切換到）或繼續 ETV 單藥治療 48 週。主要終點是第 48 週時的 HBeAg 血清學轉換。

結果：共有 153 名患者被隨機分為三個治療組（50 名附加治療組、52 名轉換治療組和 51 名單藥治療組）。與連續 ETV 單藥治療相比，附加策略和轉換策略均實現了更高的 HBeAg 血清轉換率（分別為 18.0% 和 2.0%，p = 0.007；19.2% 和 2.0%，p = 0.005），HBeAg 消失（ 24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001，分別）和更高的 HBsAg 降低（-0.90 與 -0.06 log10 IU/ml，p < 0.001；-0.92 與 -0.06 log10 IU/ml，p < 0.001，分別）在第 48 週。附加臂和切換臂之間具有可比性（p > 0.05）。不良事件主要與 PEG-IFN 相關，但通常可以耐受。

結論：在通過長期 ETV 治療獲得病毒學應答的 CHB 患者中，與連續 ETV 單藥治療相比，添加和轉換為 PEG-IFN 治療是導致 HBeAg 血清轉換率更高和 HBsAg 降低率更高的替代策略。

臨床試驗註冊：中國臨床試驗註冊中心（www.chictr.org.cn，標識符：ChiCTR-IPR-17012055）。

© 2022 John Wiley & Sons Ltd.

StephenW

The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: A multicentre randomised controlled trial
Qiankun Hu  1 , Xun Qi  1 , Yiqi Yu  2 , Yueqiu Gao  3 , Xinxin Zhang  4 , Qianqian Wang  1 , Xueyun Zhang  2 , Yunhui Zhuo  3 , Jing Li  4 , Jiming Zhang  2 , Liang Chen  1 , Yuxian Huang  1   2
Affiliations
Affiliations

    1
    Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
    2
    Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
    3
    Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
    4
    Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    PMID: 36128636 DOI: 10.1111/apt.17222

Abstract

Background & aims: The strategies of adding on or switching to peginterferon (PEG-IFN) therapy improved the serological response rates in nucleos(t)ide analogues experienced chronic hepatitis B (CHB) patients. However, robust data on which combination strategy is more effective remain lacking.

Methods: In this multicentre, parallel, open-label, randomised, controlled trial, HBeAg-positive CHB patients with entecavir (ETV) treatment ≥2 years, hepatitis B surface antigen (HBsAg) <3000 IU/ml, HBeAg <200S/CO and HBV DNA <50 IU/ml were randomly assigned in a 1:1:1 ratio to add on PEG-IFN (add-on), switch to PEG-IFN (switch-to) or continue ETV monotherapy for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48.

Results: A total of 153 patients were randomised into three treatment arms (50 in add-on, 52 in switch-to and 51 in monotherapy). Compared with continuous ETV monotherapy, both add-on and switch-to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, p = 0.007; 19.2% vs. 2.0%, p = 0.005, respectively), HBeAg loss (24.0% vs. 5.9%, p = 0.010; 23.1% vs. 5.9%, p = 0.013, respectively), HBsAg < 100 IU/ml (30.0% vs. 0%, p < 0.001; 34.6% vs. 0%, p < 0.001, respectively), and higher HBsAg reduction (-0.90 vs. -0.06 log10 IU/ml, p < 0.001; -0.92 vs. -0.06 log10 IU/ml, p < 0.001, respectively) at week 48. The efficacy was comparable between add-on and switch-to arms (p > 0.05). Adverse events were mainly related to PEG-IFN but generally tolerable.

Conclusion: In CHB patients who achieved virological response with long-term ETV treatment, both adding on and switching to PEG-IFN therapy are alternative strategies to result in higher rates of HBeAg seroconversion and higher HBsAg reduction compared with continuous ETV monotherapy.

Clinical trials registration: Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR-IPR-17012055).

© 2022 John Wiley & Sons Ltd.