King's College London Faculty of Life Sciences & Medicine.
Paediatric Liver, Gastrointestinal and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, United Kingdom.
J Pediatr Gastroenterol Nutr. 2021 Aug 1;73(2):156-160. doi: 10.1097/MPG.0000000000003118.
Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB.
Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group.
Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events.
The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.
慢性乙型肝炎(CHB)治疗指南不建议对疾病免疫耐受期的患者进行抗病毒治疗,该期通常发生于垂直获得乙型肝炎病毒(HBV)的儿童,且可能持续数十年。基于一项初步研究的良好结果,我们开展了一项随机、对照、多中心研究,以评估抗病毒治疗在免疫耐受期 CHB 儿童和青少年中的疗效和安全性。
59 例年龄 3 至<18 岁、乙型肝炎 e 抗原阳性、HBV DNA 载量>20000IU/ml 且持续正常丙氨酸氨基转移酶水平的患儿被随机分配至接受 56 周抗病毒治疗(口服核苷类似物[恩替卡韦或拉米夫定],联合第 8 周起皮下注射聚乙二醇干扰素 alfa-2a),或接受 80 周未治疗观察。主要疗效终点为抗病毒治疗组治疗 24 周后或对照组观察结束时乙型肝炎表面抗原丢失。
在两项类似研究的结果显示,类似的抗病毒方案对免疫耐受期 CHB 的儿童和成人无效后,入组即被终止。治疗 24 周后,抗病毒治疗组 26 例患者中有 1 例发生 HBsAg 丢失(对照组 33 例患者均无)。未报告严重的治疗相关不良事件,也无患者因不良事件而停止治疗。
本试验评估的抗病毒方案具有可接受的耐受性,但对免疫耐受期 CHB 的儿童和青少年无效。