[A randomized controlled study on factors influencing the curative effect of sequential combined interferon and lamivudine therapy in children with immune-tolerant phase chronic hepatitis B].
[A randomized controlled study on factors influencing the curative effect of sequential combined interferon and lamivudine therapy in children with immune-tolerant phase chronic hepatitis B].
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DOI：
10.3760/cma.j.issn.1007-3418.2019.08.004
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发表时间：
2019-08-20
影响因子：
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通讯作者：
Zhao, P
中科院分区：
文献类型：
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作者：
Zhu, S S;Dong, Y;Zhao, P
目的：探讨儿童慢性B型肝炎免疫耐受期抗病毒治疗的疗效及影响疗效的相关因素。研究方法：2014年5月至2015年4月，纳入46例慢性B型肝炎患儿，年龄1 ~ 16岁，免疫耐受期，作为治疗组。治疗组的所有病例要么接受干扰素α（3-5 MIU/m2，每日1次）联合拉米夫定治疗（如果HBV DNA下降< 2 log（10）），要么重复接受干扰素α治疗（如果HBV DNA下降>2 log（10）），持续12周。在72周时停用干扰素，并继续使用拉米夫定随访24周。同时收集23例未经治疗的免疫耐受期慢性B型肝炎患儿作为对照组。治疗组和对照组分为1-7岁和7-15岁两个年龄组。计量资料比较采用t检验、方差分析和单因素分析，计数资料采用卡方检验。采用多元Logistic回归分析不同因素对疗效的影响。结果：（1）治疗组1-7岁22例（47.8%），对照组1-7岁12例（52.2%）。治疗组和对照组母婴传播（MTCT）分别为34例（73.9%）和17例（73.9%），治疗组和对照组基线ALT正常分别为18例（39.1%）和10例（43.5%）。(2)随访结束时，治疗组HBeAg血清学转换15例（32.6%）。其中9例（19.6%）HBsAg转阴或HB-Ag阳转伴抗-HBs，1例（2.2%）HBsAg转阴但HBeAg和抗-HBe均阳性。对照组1例HBV DNA低于检测下限，1例HBeAg血清转换但HBsAg未清除。(3)随访结束时，1 ~ 7岁组和7 ~ 15岁组HBeAg阳转率分别为45.5%和20.8%（P = 0.078），HBsAg转阴率分别为36.4%和8.3%（P = 0.023）。丙氨酸氨基转移酶正常和异常的血清转换率分别为5.6%和50.0%（P = 0.005），HBsAg清除率分别为5.6%和32.1%（P = 0.077）。儿童性别、母婴传播、HBV DNA分型及基线HBsAg水平对抗病毒疗效的影响差异无统计学意义（P > 0.05）。(4)治疗24周时，随访结束时，100%的HBsAg <3000 IU/ml的患者的HBsAg和HBeAg清除率。(5)多因素Logistic回归分析显示，HBeAg阴转率与非母婴传播及基线谷丙转氨酶异常有关。此外，HBsAg清除率与儿童的年龄有关。结论：干扰素与拉米夫定序贯联合治疗可提高7岁以下免疫耐受期慢性B型肝炎患儿的HBV DNA阴转率、HBeAg血清转换率、HBsAg转阴率及ALT轻度异常。
Objective: To investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B. Methods: From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m(2), once daily) in lamivudine combination (if HBV DNA decreased < 2 log(10)) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log(10)) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by chi (2) test. Multiple logistic regression analysis was used to analyze the effects of different factors on response. Results: (1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children. Conclusion: Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.