Ballauff A, Schneider T, Gerner P, Habermehl P, Behrens R, Wirth S
Department of Paediatrics, University of Essen, Germany.
Eur J Pediatr. 1998 May;157(5):382-5. doi: 10.1007/s004310050834.
More than 50% of children with chronic hepatitis B do not respond to treatment with alpha-interferon. Since these patients continue to display high viral replication and progressive liver disease, retreatment should be considered. To date it has not been well evaluated whether a second course of treatment could increase the response rate. In two alpha-interferon retreatment trials in adult patients the response rate, defined by seroconversion from HBeAg to anti-HBe, ranged between 11% and 44%. One beta-interferon retreatment study in children reported a seroconversion rate of 32%. Regrettably, none of the studies included a control group observing the 'spontaneous' seroconversion rate after a first interferon cycle. Thus, a nonrandomized alpha-interferon retreatment study in children including control patients was performed. Alpha-interferon for retreatment was administered 3 times a week for 16-24 weeks in 15 children (5-16 years) at least 6 months after ceasing the first cycle. Four children received 5 MU/m2 of a natural alpha-interferon and 11 children 9 MU/m2 recombinant alpha-interferon 2b. Follow up was 18-47 months after initial treatment. In parallel, a control group of 19 unretreated children with comparable clinical and demographic data was followed for 12-39 months. HBeAg seroconversion was observed in 5 (33%) of the retreated children and in 5 (26%) of the control patients during follow up. The difference is not significant. In the initially nonresponding children, those with high ALT levels before the first treatment showed late HBeAg seroconversion more frequently than those with low ALT levels (P=0.017) irrespective of retreatment. The ALT level before retreatment was not a predictor for response.
A second cycle of alpha-interferon during the 3 years following the first treatment in nonresponding children with chronic hepatitis B can be safely performed but did not increase HBeAg/anti-HBe seroconversion compared with the spontaneous seroconversion rate of patients without retreatment.
超过50%的慢性乙型肝炎儿童对α干扰素治疗无反应。由于这些患者持续表现出高病毒复制和进行性肝病，应考虑再次治疗。迄今为止，尚未很好地评估第二个疗程的治疗是否能提高应答率。在两项针对成年患者的α干扰素再次治疗试验中，由HBeAg血清学转换为抗-HBe所定义的应答率在11%至44%之间。一项针对儿童的β干扰素再次治疗研究报告血清学转换率为32%。遗憾的是，这些研究均未纳入观察第一个干扰素疗程后“自然”血清学转换率的对照组。因此，开展了一项针对儿童的非随机α干扰素再次治疗研究，纳入了对照患者。在15名（5 - 16岁）儿童中，在第一个疗程结束至少6个月后，给予再次治疗的α干扰素，每周3次，共16 - 24周。4名儿童接受5 MU/m²的天然α干扰素，11名儿童接受9 MU/m²的重组α干扰素2b。初始治疗后随访18 - 47个月。同时，对19名具有可比临床和人口统计学数据的未接受再次治疗的儿童组成的对照组进行了12 - 39个月的随访。随访期间，再次治疗的儿童中有5名（33%）出现HBeAg血清学转换，对照患者中有5名（26%）出现HBeAg血清学转换。差异无统计学意义。在最初无反应的儿童中，首次治疗前ALT水平高的儿童比ALT水平低的儿童更频繁地出现晚期HBeAg血清学转换（P = 0.017），与是否再次治疗无关。再次治疗前的ALT水平不是应答的预测指标。
在慢性乙型肝炎无反应儿童首次治疗后的3年内，第二个α干扰素疗程可安全进行，但与未接受再次治疗患者的自然血清学转换率相比，并未提高HBeAg/抗-HBe血清学转换率。
