Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
J Med Virol. 2022 Nov;94(11):5475-5483. doi: 10.1002/jmv.28003. Epub 2022 Jul 19.
Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable in hepatitis B e-antigen (HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated. This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety. No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group. Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration: ChiCTR1800016173.
乙型肝炎表面抗原（HBsAg）丢失或血清转换是慢性乙型肝炎患者的理想治疗终点，但在使用现有治疗策略的乙型肝炎 e 抗原（HBeAg）阳性患者中很少能实现。本研究评估了聚乙二醇干扰素（peg-IFN）alfa-2b 加替诺福韦酯（TDF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和乙型肝炎疫苗的疗效。这项随机对照试验于 2018 年 5 月至 2020 年 7 月在中国大学医院的九个肝脏中心进行。招募的患者（n=303）被随机分为 peg-IFN-α-2b 联合 TDF、GM-CSF 和乙型肝炎疫苗（实验组）；peg-IFN-α-2b 加 TDF（对照组 2）；或单独使用干扰素-α-2b（对照组 1）。主要疗效终点为 48 周时 HBsAg 血清转换，次要终点包括安全性。各组基线 HBsAg 水平无差异。实验组有 3 例（3.0%）、对照组 2 有 1 例（1.03%）和对照组 1 有 1 例（1.19%）达到主要终点。三组患者在第 48 周时 HBsAg 血清转换的发生率无显著差异（p=0.629）。然而，实验组和对照组 2 在第 48 周时 HBsAg 血清水平下降明显高于对照组 1（p=0.008 和 0.006）。实验组和对照组 2 之间无显著差异（p=0.619）。除实验组中性粒细胞减少发生率较低外，各组不良反应无显著差异。与 peg-IFN-α-2b 联合 TDF 相比，peg-IFN-α-2b 联合 TDF、GM-CSF 和乙型肝炎疫苗在 HBeAg 阳性初治患者中并不优越。临床试验注册：ChiCTR1800016173。
