Peginterferon Alfa-2a（40KD）加拉米夫定或恩替卡韦治疗儿童免疫

StephenW

Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children with Immune-tolerant Chronic Hepatitis B
Giorgina Mieli-Vergani  1 , Sanjay Bansal, James F Daniel, Aydan Kansu, Deirdre Kelly, Carmen Martin, Sarah Tizzard, Stefan Wirth, Julian Zhou, Diego Vergani
Affiliations
Affiliation

    1
    King's College London Faculty of Life Sciences & Medicine, London, United Kingdom Paediatric Liver, Gastrointestinal and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, United Kingdom Children's Mercy Hospital, Kansas City, Kansas, United States Department of Pediatric Gastroenterology, Ankara University School of Medicine, Ankara, Turkey Liver Unit, Birmingham Women's & Children's Hospital and University of Birmingham, Birmingham, United Kingdom Roche Products Limited, Welwyn Garden City, United Kingdom Department of Pediatrics, Helios Medical Center Wuppertal, Witten-Herdecke University, Germany RochePharma Product Development Shanghai, Shanghai, China Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.

    PMID: 33720089 DOI: 10.1097/MPG.0000000000003118

Abstract

Objective: Treatment guidelines for chronic hepatitis B (CHB) do not recommended 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.

Methods: Fifty-nine children aged 3 to <18 years HBe antigen-positive with an HBV DNA titer >20000 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 HBsAg loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group.

Results: 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, one 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.

Conclusions: The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology.

StephenW

Peginterferon Alfa-2a（40KD）加拉米夫定或恩替卡韦治疗儿童免疫耐受性慢性乙型肝炎
Giorgina Mieli-Vergani 1，Sanjay Bansal，James F Daniel，Aydan Kansu，Deirdre Kelly，Carmen Martin，Sarah Tizzard，Stefan Wirth，Julian Zhou，Diego Vergani
隶属关系
联系

    1个
    伦敦金斯学院伦敦生命科学与医学学院，英国伦敦小儿肝脏，胃肠病和营养中心，金斯学院医院NHS Foundation Trust，英国伦敦儿童慈善医院，堪萨斯州，堪萨斯州，美国儿科胃肠病学，安卡拉土耳其安卡拉大学医学院，伯明翰妇女儿童医院肝脏科，英国伯明翰伯明翰大学罗氏产品有限公司，英国韦林花园市，儿科，德国威滕-赫德克大学伍珀塔尔Helios医学中心上海罗氏药业产品开发有限公司，上海，英国伦敦国王学院医院中国肝病研究所，NHS基金会信托。

    PMID：33720089 DOI：10.1097 / MPG.0000000000003118

抽象的

目的：慢性乙型肝炎（CHB）的治疗指南不建议对处于免疫耐受阶段的患者进行抗病毒治疗，这种治疗通常发生在垂直感染乙型肝炎病毒（HBV）的儿童中，可能持续数十年。基于一项前瞻性研究的有希望的结果，我们进行了一项随机，对照，多中心研究，以评估抗病毒治疗对具有免疫耐受性CHB的儿童和青少年的疗效和安全性。

方法：将59名3至18岁HBe抗原阳性，HBV DNA滴度> 20000 IU / mL且丙氨酸转氨酶水平持续正常的儿童随机分配至口服核苷类似物[恩替卡韦或拉米夫定]抗病毒治疗56周，与第8周或未经治疗的80周观察到的皮下聚乙二醇干扰素alfa-2a联合使用。主要疗效结果是抗病毒治疗组治疗后24周或对照组观察结束时HBsAg丢失。

结果：两项相似的研究结果表明，相似的抗病毒方案对具有免疫耐受性CHB的儿童和成人无效，因此终止了研究。在治疗后24周，抗病毒治疗组26例患者中的1例经历了HBsAg丢失（与之相比，对照组33例中无1例）。没有报告严重的与治疗有关的不良事件，也没有患者因不良事件而中止治疗。

结论：该试验评估的抗病毒方案具有可接受的耐受性，但对具有免疫耐受性CHB的儿童和青少年无效。

欧洲小儿胃肠病，肝病和营养学会和北美小儿胃肠病学会版权所有©2021。