Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B
Long-term efficacy and safety of peginterferon in the treatment of children with HBeAg-positive chronic hepatitis B
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DOI：
10.1111/jvh.13154
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发表时间：
2019-07-01
影响因子：
2.5
通讯作者：
Wei, Jia
中科院分区：
文献类型：
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作者：
Liu, Yunhua;Li, Hui;Wei, Jia
通过安全有效的抗病毒治疗实现慢性B型肝炎（CH B）儿童的“临床治愈”是一个未满足的医疗需求。聚乙二醇干扰素（PegIFN）对B s抗原（HBsAg）的清除率高于核苷类似物（NUC）。目前，关于干扰素（IFN）治疗中国儿童CHB的研究相对较少。本研究旨在进一步探讨聚乙二醇干扰素α-2a在中国儿童中作为抗病毒治疗的疗效，并分析停药后的长期随访。我们纳入了作者于2009年2月至2015年2月在昆明市第三人民医院接受聚乙二醇干扰素α-2a治疗的118例慢性乙型肝炎患者（2-16岁，79例为男性）。疗程为52周，随访期为104周。所有患者均完成至少1次给药，其中104例完成至少36周治疗和104周随访。在治疗和随访期间，监测丙氨酸氨基转移酶（ALT）、B型肝炎病毒（HBV）DNA和HBV血清学标志物等指标，观察聚乙二醇干扰素α-2a治疗CH B患者的疗效和安全性。停药时，B e抗原（HBeAg）清除率和血清转换率分别为53.8%和49%;随访结束时分别为72.1%和72.1%;持续应答分别为98.2%和98%。停药时HBsAg清除率和血清转换率分别为48.1%和47.1%;随访结束时分别为53.8%和52.9%;持续应答分别为94%和95.9%。停药时HBV DNA抑制率为89.4%，随访结束时为90.4%，持续缓解为97.8%。两名患者在随访期间出现病毒学复发（2.3%），但未发生临床复发。多变量回归分析显示，基因型B、体重< 25 kg或25 - 45 kg、治疗24周后HBsAg下降超过1 log是随访结束时HBsAg清除的独立预测因素。治疗期间发生的不良事件与既往PegIFN临床研究报告的不良事件相似。本研究结果表明，聚乙二醇干扰素治疗儿童慢性乙型肝炎安全有效，治疗后可获得持续应答。PegIFN治疗儿童CHB有助于更多地实现“临床治愈”。
Achieving 'clinical cure' in children with chronic hepatitis B (CHB) with safe and effective antiviral treatment is an unmet medical need. Peginterferon (PegIFN) has higher hepatitis B s antigen (HBsAg) clearance than nucleoside analogs (NUC). Currently, studies on interferon (IFN) in the treatment of Chinese children with CHB are relatively rare. This study aimed to further explore the efficacy of PegIFN alpha-2a as an antiviral treatment in Chinese children and analyse the long-term follow-up after drug discontinuation. We enrolled 118 patients with CHB (2-16 years old, 79 cases are males) treated with PegIFN alpha-2a by the author in the Third People's Hospital of Kunming City from February 2009 to February 2015. The course of treatment was 52 weeks, with a follow-up period of 104 weeks. All the patients completed at least 1 dose, of which 104 completed at least 36 weeks of treatment and 104 weeks of follow-up. During treatment and follow-up, indicators such as alanine aminotransferase (ALT), hepatitis B virus (HBV) DNA and HBV serological markers were monitored, and the efficacy and safety of PegIFN alpha-2a in the treatment of CHB patients were observed. Hepatitis B e antigen (HBeAg) clearance and seroconversion rates were 53.8% and 49%, respectively, when the drug was discontinued; 72.1% and 72.1%, respectively, at the end of the follow-up; and 98.2% and 98%, respectively, for sustained response. HBsAg clearance and seroconversion rates were 48.1% and 47.1%, respectively, when the drug was discontinued; 53.8% and 52.9%, respectively, at the end of the follow-up; and 94% and 95.9%, respectively, for sustained response. The HBV DNA suppression rate was 89.4% when the drug was discontinued, 90.4% at the end of the follow-up and 97.8% for sustained response. Two patients had virological relapse (2.3%) during follow-up; however, no clinical relapse occurred. Multivariate regression analysis showed that genotype B, weight < 25 kg or between 25 and 45 kg, and reduction of HBsAg by more than 1 log following 24 weeks of treatment were independent predictors of HBsAg clearance at the end of follow-up. Adverse events that occurred during treatment were similar to those reported in previous clinical studies on PegIFN. The results of this study showed that PegIFN was safe and effective in the treatment of children with CHB, and sustained response could be achieved after treatment. PegIFN treatment of children with CHB helps more achieve 'clinical cure'.