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Abstract：
OBJECTIVE: 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.
METHODS: 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/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：关于替诺福韦艾拉酚胺（TAF）加聚乙二醇干扰素-α（Peg-IFN-α）在慢性乙型肝炎（CHB）儿童中的安全性和有效性的数据缺乏。目前的研究旨在呈现谁通过使用TAF和PEG-IFN-α获得功能性治愈的四个儿科CHB患者的特征。
方法：在2019年5月开始的病例系列研究中，10名没有临床症状或体征的儿童接受了应答指导（HBVDNA检测不到，乙型肝炎e抗原[HBeAg]丢失或血清转换，和乙型肝炎表面抗原[HBsAg]损失或血清转换）和功能性治愈靶向（HBsAg损失或血清转换）TAF（25毫克/天，口服）加PEG-IFN-α-2b（180µg/1.73m2，皮下，每周一次）联合（9/10）或序贯（1/10）治疗。监测这些治疗的安全性和有效性。
结果：截至2024年4月，在平均31.5个月的治疗后，十分之四的儿童获得了功能性治愈，其他六个孩子仍在接受治疗。这四个治愈的孩子，2岁、4岁、8岁和6岁，均为HBeAg阳性，丙氨酸转氨酶水平为80，47，114和40U/L;HBVDNA水平为71200000，93000000，8220和96700000IU/mL;HBsAg水平为39442.8，15431.2，22和33013.1IU/mL，分别。治疗期间,所有儿童（10/10）都经历了轻度或中度不良事件，包括流感样症状，厌食症,疲劳,和血细胞减少症。值得注意的是,生长迟缓(8/10)是最显著的不良事件;在接受联合治疗的3名治愈儿童(3/4)中发生,在接受序贯治疗的另1名治愈儿童(1/4)中出现的程度较低.幸运的是,所有3名治愈儿童在治疗后9个月恢复或超过正常生长水平.
结论：TAF加PEG-IFN-α-2b治疗是潜在的安全和有效的儿科CHB患者，这可能为未来的临床实践和针对CHB儿童功能性治疗的研究设计提供重要的见解。
方法：在2019年5月开始的病例系列研究中，10名没有临床症状或体征的儿童接受了应答指导（HBVDNA检测不到，乙型肝炎e抗原[HBeAg]丢失或血清转换，和乙型肝炎表面抗原[HBsAg]损失或血清转换）和功能性治愈靶向（HBsAg损失或血清转换）TAF（25毫克/天，口服）加PEG-IFN-α-2b（180µg/1.73m2，皮下，每周一次）联合（9/10）或序贯（1/10）治疗。监测这些治疗的安全性和有效性。
结果：截至2024年4月，在平均31.5个月的治疗后，十分之四的儿童获得了功能性治愈，其他六个孩子仍在接受治疗。这四个治愈的孩子，2岁、4岁、8岁和6岁，均为HBeAg阳性，丙氨酸转氨酶水平为80，47，114和40U/L;HBVDNA水平为71200000，93000000，8220和96700000IU/mL;HBsAg水平为39442.8，15431.2，22和33013.1IU/mL，分别。治疗期间,所有儿童（10/10）都经历了轻度或中度不良事件，包括流感样症状，厌食症,疲劳,和血细胞减少症。值得注意的是,生长迟缓(8/10)是最显著的不良事件;在接受联合治疗的3名治愈儿童(3/4)中发生,在接受序贯治疗的另1名治愈儿童(1/4)中出现的程度较低.幸运的是,所有3名治愈儿童在治疗后9个月恢复或超过正常生长水平.
结论：TAF加PEG-IFN-α-2b治疗是潜在的安全和有效的儿科CHB患者，这可能为未来的临床实践和针对CHB儿童功能性治疗的研究设计提供重要的见解。
