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。
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.