Entecavir加聚乙二醇化干扰素和顺序性HBV疫苗接种可提高HBsAg血

StephenW

Entecavir Plus Pegylated Interferon and Sequential HBV Vaccination Increases HBsAg Seroclearance: A Randomized Controlled Proof-of-Concept Study
Jeong-Hoon Lee  1 , Yun Bin Lee  1 , Eun Ju Cho  1 , Su Jong Yu  1 , Jung-Hwan Yoon  1 , Yoon Jun Kim  1
Affiliations
Affiliation

    1
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

    PMID: 32556157 DOI: 10.1093/cid/ciaa807

Abstract

Background: HBsAg seroclearance is considered a functional cure for patients with chronic hepatitis B, but is rarely achievable with oral nucleos(t)ide analogs alone. We conducted a randomized controlled proof-of-concept trial to evaluate the impact of adding pegylated interferon (Peg-IFN) alfa-2a plus sequential or concomitant hepatitis B virus (HBV) vaccination.

Methods: A total of 111 patients who achieved serum HBV DNA <20 IU/mL and quantitated HBsAg (qHBsAg) <3,000 IU/mL with entecavir were randomly assigned (1:1:1) to the E+sVIP group (entecavir + Peg-IFN alfa-2a [180 µg every week over 48 weeks] + sequential HBV vaccination [20 µg of HBsAg on weeks 52, 56, 60, and 76]), E+cVIP group (entecavir + Peg-IFN alfa-2a + concomitant HBV vaccination [weeks 4, 8, 12, and 28]), or the control group (entecavir only). The primary endpoint was HBsAg seroclearance at week 100 and secondary endpoints included safety.

Results: No differences in baseline qHBsAg were observed among the groups. The E+sVIP group in the intention-to-treat analysis showed a significantly higher chance of HBsAg seroclearance during week 100 than the control group (16.2% vs. 0%, P=0.025), but the E+cVIP group (5.4%) failed to reach a significant difference (P=0.54). Adverse events were significantly more frequent in the E+sVIP (81.1%) or E+cVIP group (70.3%) than the control group (2.7%) (both P<0.0001). However, the frequency of serious adverse events did not differ significantly among three groups (2.7%, 5.4%, and 2.7%, respectively; P=1.00).

Conclusions: Entecavir plus an additional Peg-IFN alfa-2a treatment followed by sequential HBV vaccination under an intensified schedule significantly increases the chance of HBsAg seroclearance compared to entecavir alone.

Keywords: functional cure; hepatitis B virus; nucleoside analogue; therapeutic vaccination.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]

StephenW

Entecavir加聚乙二醇化干扰素和顺序性HBV疫苗接种可提高HBsAg血清清除率：一项随机对照概念验证研究
李正勋1，李允彬1，恩珠祖1，苏钟宇1，郑焕焕1，尹俊金1
隶属关系
联系

    1个
    首尔国立首尔大学医学院内科与肝脏研究所。

    PMID：32556157 DOI：10.1093 / cid / ciaa807

抽象

背景：HBsAg血清清除被认为是慢性乙型肝炎患者的一种功能性治愈方法，但仅靠口服核苷类似物很难达到。我们进行了一项随机对照概念验证试验，以评估添加聚乙二醇化干扰素（Peg-IFN）alfa-2a以及相继或伴随的乙肝病毒（HBV）疫苗接种的影响。

方法：将111名血清恩替卡韦的HBV DNA <20 IU / mL且定量HBsAg（qHBsAg）<3,000 IU / mL的患者随机（1：1：1）分配至E + sVIP组（恩替卡韦+聚乙二醇-IFN alfa-2a [在48周内每周180 µg] +连续HBV疫苗接种[52、56、60和76周时分别接受20 µg HBsAg]，E + cVIP组（恩替卡韦+ Peg-IFN alfa-2a + HBV疫苗接种（第4、8、12和28周）或对照组（仅恩替卡韦）。主要终点是在第100周时的HBsAg血清清除，次要终点包括安全性。

结果：各组之间未观察到基线qHBsAg差异。意向性治疗分析中的E + sVIP组在100周内显示出HBsAg血清清除的机会明显高于对照组（16.2％vs. 0％，P = 0.025），但是E + cVIP组（5.4％） ）未能达到显着差异（P = 0.54）。 E + sVIP组（81.1％）或E + cVIP组（70.3％）的不良事件比对照组（2.7％）的发生率显着更高（均P <0.0001）。但是，三组中严重不良事件的发生率没有显着差异（分别为2.7％，5.4％和2.7％； P = 1.00）。

结论：与单独使用恩替卡韦相比，恩替卡韦联合其他Peg-IFN alfa-2a治疗后在强化方案下依次进行HBV疫苗接种可显着增加HBsAg血清清除的机会。

关键字：功能性治疗；乙型肝炎病毒;核苷类似物;治疗性疫苗接种。

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