重组人干扰素α-2b和拉米夫定序贯治疗免疫耐受期慢性乙型肝炎患儿的临床疗效观察

Efficacy of sequential therapy with recombinant human interferon α-2b and lamivudine in children with chronic hepatitis B in immune-tolerant phase

摘要:

目的 观察重组人干扰素α-2b和拉米夫定序贯治疗免疫耐受期慢性乙型肝炎患儿的临床疗效和安全性。方法 将145例免疫耐受期慢性乙型肝炎患儿随机分为对照组72例和实验组73例。对照组给予拉米夫定片，0.1 g/次，1次/d，口服，治疗24周；实验组给予重组人干扰素α-2b和拉米夫定，前4周单用重组人干扰素α-2b，5 mIU/（m²·次），1次/2 d，肌内或皮下注射，4周后加用拉米夫定片，0.1 g/次，1次/d，口服，持续治疗8周，然后停用重组人干扰素α-2b，仅单用拉米夫定片（用药剂量不变），继续治疗12周。比较两组治疗前和治疗后6周、12周和24周的丙氨酸氨基转移酶（ALT）、HBeAg转阴率和HBV-DNA转阴率，以及临床疗效和安全性。结果 实验共脱落3例。对照组与实验组治疗前和治疗后6周、12周和24周的ALT水平比较，采用重复测量设计的方差分析，结果 ①不同时间点ALT水平无差异（F =0.214，P =0.505）；②对照组与实验组ALT水平无差异（F =0.301，P =0.422）；③两组ALT水平变化趋势无差异（F =0.147，P =0.721）。实验组治疗后24周的HBeAg转阴率、HBV-DNA转阴率、总有效率、总不良反应发生率高于对照组（P <0.05）。实验组的药物不良反应主要有白细胞一过性减少、发热、腹泻、头痛，对照组的药物不良反应主要有发热、腹泻、头痛。结论 重组人干扰素α-2b和拉米夫定序贯治疗免疫耐受期慢性乙型肝炎患儿的疗效更佳，但加用重组人干扰素α-2b时会产生白细胞一过性减少，停药后症状消失，可根据患儿情况酌情使用。

Abstract:

Objective To observe the clinical efficacy and safety of sequential therapy with recombinant human interferon α-2b and lamivudine in children with chronic hepatitis B in immune-tolerant phase.Methods A total of 145 children with chronic hepatitis B in immune-tolerant phase were randomly divided into control group (72 cases) and test group (73 cases). The control group was given lamivudine orally at a dose of 0.1 g once a day for 24 weeks. The experimental group was given recombinant human interferon α-2b and lamivudine. In the first 4 weeks, the single therapy with recombinant human interferon α-2b was administrated intramuscularly or subcutaneously at a dose of 5 mIU/m² every 2 days. After 4 weeks, lamivudine was added orally at a dose of 0.1 g once a day for 8 weeks. Then recombinant human interferon α-2b was discontinued, and lamivudine was used alone for another 12 weeks with the dosage unchanged. The level of alanine aminotransferase (ALT) and the negative conversion ratios of HBeAg and HBV-DNA before and 6, 12 and 24 weeks after the treatment, as well as the clinical efficacy and safety, were compared between the two groups.Results Three cases were lost to the follow-up during the treatment. The level of ALT before and 6, 12 and 24 weeks after the treatment in the control group and the test group were compared via repeated measures analysis of variance, and the results showed that there was no significant difference in the level of ALT at different time points (F = 0.214, P = 0.505) and between the groups (F =0.301, P = 0.422), and that the change trend of the level of ALT was not different between the two groups (F =0.147, P = 0.721). After 24 weeks of treatment, the negative conversion ratios of HBeAg and HBV-DNA, the overall effective rate, and the overall incidence of adverse reactions in the test group were higher than those in the control group (P < 0.05). The adverse drug reactions in the test group mainly included transient leucopenia, fever, diarrhea and headache, while those in the control group mainly included fever, diarrhea and headache.Conclusions Sequential therapy with recombinant human interferon α-2b and lamivudine is more effective than lamivudine alone in the treatment of children with chronic hepatitis B in immune-tolerant phase. However, the addition of recombinant human interferon α-2b may lead to transient leucopenia and symptoms that will disappear after drug withdrawal. Thus, the sequential therapy could be taken into consideration where appropriate.