Wang Xin, Lai Changxiang, Li Ruiling, Lei Jia, Xie Yuyin, Li Zhiyu, Tang Qiyuan, He Qing, Zhang Hongfei, Zhang Zheng, Wang Fang
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China.
Department of Liver Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China.
Emerg Microbes Infect. 2025 Dec;14(1):2516173. doi: 10.1080/22221751.2025.2516173. Epub 2025 Jun 26.
Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection in children and adolescents with normal alanine aminotransferase (ALT) levels constitutes a substantial population in China, yet the optimal timing for antiviral therapy remains unclear. This prospective, real-world study, conducted as the primary centre of the Sprout Project, evaluated the hepatitis B surface antigen (HBsAg) loss rate and viral-immune dynamics of pegylated interferon α (PEG-IFN-α) treatment in 85 chronic HBV patients aged 3-18 years over a 24-month period. A total of 27 HBeAg-positive, ALT-normal patients were selected for analysis. Patients were treated with a combination of PEG-IFN-α and entecavir. After 24 months, the overall HBsAg loss rate was 48.15%, with 47.37% in the immune-tolerant phase and 50% in the grey zone phase. Among those who cleared HBsAg, 84.62% had ALT elevation prior to anti-HBsAg antibody (HBsAb) seroconversion, which occurred 28-400 days before HBsAg loss. While HBsAg and HBV DNA were cleared by 24 months in the HBsAg loss group, 23.08% of children remained HBeAg-positive. Notably, 61.54% developed detectable HBsAb prior to HBsAg loss. Children aged 3-7 years had significantly higher clearance rates than those aged 8-18 years. These findings support the effectiveness of PEG-IFN-α combined with nucleos(t)ide analogs in achieving high HBsAg loss rates in young, HBeAg-positive, ALT-normal chronic HBV children and adolescents, with immune activation potentially preceding ALT elevation, and offers valuable insights into the viral-immune dynamics during treatment, highlighting the potential of antiviral therapy in this population.
在中国，丙氨酸氨基转移酶（ALT）水平正常的儿童和青少年中，乙肝e抗原（HBeAg）阳性的慢性乙型肝炎病毒（HBV）感染构成了一个庞大群体，但抗病毒治疗的最佳时机仍不明确。这项前瞻性的真实世界研究作为萌芽项目的主要中心开展，评估了85例3至18岁慢性HBV患者在24个月期间接受聚乙二醇干扰素α（PEG-IFN-α）治疗的乙肝表面抗原（HBsAg）清除率和病毒免疫动态。共选择27例HBeAg阳性、ALT正常的患者进行分析。患者接受PEG-IFN-α与恩替卡韦联合治疗。24个月后，总体HBsAg清除率为48.15%，免疫耐受期为47.37%，灰色区阶段为50%。在清除HBsAg的患者中，84.62%在抗HBsAg抗体（HBsAb）血清学转换前出现ALT升高，这发生在HBsAg清除前28至400天。虽然HBsAg丢失组在24个月时清除了HBsAg和HBV DNA，但23.08%的儿童HBeAg仍为阳性。值得注意的是，61.54%在HBsAg丢失前出现可检测到的HBsAb。3至七岁的儿童清除率明显高于8至18岁的儿童。这些发现支持PEG-IFN-α联合核苷（酸）类似物在年轻的、HBeAg阳性、ALT正常的慢性HBV儿童和青少年中实现高HBsAg清除率的有效性，免疫激活可能先于ALT升高，并为治疗期间的病毒免疫动态提供了有价值的见解，突出了该人群抗病毒治疗的潜力。
