Department of Infectious Diseases and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
BMC Infect Dis. 2024 Aug 15;24(1):830. doi: 10.1186/s12879-024-09723-0.
Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α.
In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored.
As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment.
TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.
目前缺乏替诺福韦艾拉酚胺（TAF）联合聚乙二醇干扰素-α（Peg-IFN-α）治疗儿童慢性乙型肝炎（CHB）的安全性和有效性数据。本研究旨在报告 4 例接受 TAF 和 Peg-IFN-α 治疗后获得功能性治愈的儿童 CHB 患者的特征。
在这项 2019 年 5 月启动的病例系列研究中，10 名无临床症状或体征的儿童接受了基于应答（HBV DNA 不可检测、乙型肝炎 e 抗原[HBeAg]消失或血清转换、以及乙型肝炎表面抗原[HBsAg]消失或血清转换）和功能性治愈目标（HBsAg 消失或血清转换）的 TAF（25 mg/d，口服）联合 Peg-IFN-α-2b（180 µg/1.73m 2 ，皮下，每周 1 次）治疗（9/10 例联合治疗，1/10 例序贯治疗）。监测这些治疗的安全性和有效性。
截至 2024 年 4 月，10 例儿童中有 4 例在平均 31.5 个月的治疗后获得功能性治愈，其余 6 例仍在治疗中。这 4 例治愈的儿童年龄分别为 2、4、8 和 6 岁，均为 HBeAg 阳性，丙氨酸氨基转移酶水平分别为 80、47、114 和 40 U/L；HBV DNA 水平分别为 71200000、93000000、8220 和 96700000 IU/mL；HBsAg 水平分别为 39442.8、15431.2、22 和 33013.1 IU/mL。治疗期间，所有儿童（10/10）均出现轻度或中度不良反应，包括流感样症状、厌食、疲劳和血细胞减少。值得注意的是，生长迟缓（8/10）是最显著的不良反应；在 3 例接受联合治疗的治愈儿童（3/4）中发生，在 1 例接受序贯治疗的治愈儿童（1/4）中程度较轻。幸运的是，所有 3 例治愈儿童在治疗后 9 个月均恢复至或超过正常生长水平。
TAF 联合 Peg-IFN-α-2b 治疗儿童 CHB 具有潜在的安全性和有效性，可为儿童 CHB 功能性治愈的未来临床实践和研究设计提供重要启示。
