恩替卡韦，聚乙二醇干扰素对儿童免疫性乙型肝炎无效

StephenW

November 14, 2018
Entecavir, Peginterferon Ineffective for Immune-Tolerant Hepatitis B in Children

Researchers report a minimal response rate with this experimental treatment, with only 2 of 60 children achieving the pre-established primary efficacy end point. Researchers report a minimal response rate with this experimental treatment, with only 2 of 60 children achieving the pre-established primary efficacy end point.

For children with immune-tolerant chronic hepatitis B virus (HBV), combination entecavir and peginterferon for up to 48 weeks rarely led to the loss of hepatitis B e antigen (HBeAg) with sustained suppression of HBV DNA levels, according to results published in Hepatology.

In addition, the results indicated that this course of treatment frequently led to adverse events. The researchers, therefore, conducted a study to evaluate “the use of a highly potent nucleoside analogue in combination with peginterferon as a means of inducing a permanent remission in immune tolerant chronic HBV infection in children.”

The study included children with immune-tolerant features of chronic HBV. Participants received entecavir 0.015 mg/kg (maximum 0.5 mg) once daily for 48 weeks. After week 8, participants also received peginterferon alfa-2a 180 μg/1.73 m2 subcutaneously once weekly through week 48.

The primary end point was lack of detectable HBeAg with HBV DNA levels ≤1000 IU/mL 48 weeks after stopping therapy.

A total of 60 children with a median age of 10.9 years (range 3.4-17.9 years) were enrolled, and 55 completed the entire 48-week course of therapy.

At week 48 after treatment ended, 3% of children (n=2) achieved the primary end point and were also negative for hepatitis B surface antigen (HBsAg) and were positive for anti-HBs.

At week 60, 1 child was HBeAg positive but HBsAg negative, and at week 72, 1 child was HBeAg negative but had been HBsAg positive at last follow-up visit.

Among the other participants, serum alanine aminotransferase and HBV DNA levels at week 96 were similar to those at baseline.

Over the study period, 37 children experienced adverse events, with 1 child experiencing a serious adverse event.


“The few responses that occurred were complete and convincing which argues for increased efforts to identify better treatments for hepatitis B that might result in cure of this infection in a higher proportion of patients including children with immune tolerant phenotype of disease,” the researchers wrote.

Reference

Rosenthal P, Ling SC, Belle SH, et al. Combination of entecavir/peginterferon alfa-2a in children with HBeAg-positive immune tolerant chronic hepatitis B virus infection [published online October 15, 2018]. Hepatology. doi: 10.1002/hep.30312

StephenW

2018年11月14日
恩替卡韦，聚乙二醇干扰素对儿童免疫性乙型肝炎无效

研究人员报告了这种实验性治疗的最小反应率，60名儿童中只有2名达到了预先确定的主要疗效终点。研究人员报告了这种实验性治疗的最小反应率，60名儿童中只有2名达到了预先确定的主要疗效终点。

对于免疫耐受的慢性乙型肝炎病毒（HBV）患儿，联合恩替卡韦和聚乙二醇干扰素长达48周，很少导致乙型肝炎e抗原（HBeAg）的丢失，并持续抑制HBV DNA水平，根据Hepatology发表的结果。

此外，结果表明，这种疗程经常导致不良事件。因此，研究人员进行了一项研究，以评估“使用高效核苷类似物与聚乙二醇干扰素作为诱导儿童免疫耐受性慢性HBV感染永久缓解的手段”。

该研究包括具有慢性HBV免疫耐受特征的儿童。参与者每天一次接受恩替卡韦0.015 mg / kg（最大0.5 mg），持续48周。在第8周后，参与者还在第48周每周一次皮下注射聚乙二醇干扰素α-2a180μg/ 1.73m2。

主要终点是缺乏可检测的HBeAg，停止治疗48周后HBV DNA水平≤1000IU/ mL。

共招募了60名中位年龄为10.9岁（范围3.4-17.9岁）的儿童，55名儿童完成了为期48周的整个治疗过程。

治疗结束后第48周，3％的儿童（n = 2）达到主要终点，乙型肝炎表面抗原（HBsAg）也呈阴性，抗-HBs阳性。

在第60周，1名儿童HBeAg阳性，但HBsAg阴性，第72周，1名儿童HBeAg阴性但最后一次随访时HBsAg阳性。

在其他参与者中，第96周的血清丙氨酸氨基转移酶和HBV DNA水平与基线时相似。

在研究期间，37名儿童出现不良事件，1名儿童出现严重不良事件。


研究人员写道：“发生的少数反应是完整的，令人信服的，这些反应是为了更好地确定乙型肝炎的治疗方法，这可能会导致更高比例的患者（包括具有免疫耐受性疾病表型的儿童）治愈这种感染。”

参考

Rosenthal P，Ling SC，Belle SH，et al。恩替卡韦/聚乙二醇干扰素α-2a联合治疗HBeAg阳性免疫耐受慢性乙型肝炎病毒感染的儿童[在线发表于2018年10月15日]。肝病。 doi：10.1002 / hep.30312