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 χ (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.
目的： 通过随机对照研究探讨免疫耐受期慢性乙型肝炎儿童抗病毒治疗的疗效及影响疗效的相关因素。 方法： 2014年5月至2015年4月住院免疫耐受期慢性乙型肝炎> 1～≤16岁儿童按2∶1比例随机分配46例儿童进入治疗组，先予以干扰素α（3～5 MIU/m(2)，隔日1次）治疗12周，如HBV DNA下降<2 log(10)联合拉米夫定（3 mg·kg(-1)·d(-1)，30 kg以上100 mg/d）治疗；如HBV DNA下降≥2 log(10)继续单用干扰素α治疗。72周时停用干扰素，随访24周，随访期用拉米夫定继续治疗。收集免疫耐受期慢性乙型肝炎23例不予治疗> 1～≤16岁儿童资料作为对照组。治疗组与对照组按年龄分层为> 1～≤7岁和7～≤16岁两个年龄段。计量资料比较采用t检验，方差分析等单因素分析方法，计数资料采用χ(2)检验。用logistic多元回归方法分析不同因素对应答的影响。 结果： （1）治疗组中> 1～≤7岁儿童22例(47.8%)，对照组中> 1～≤7岁儿童12例（52.2%）。治疗组母婴传播和基线丙氨酸氨基转移酶正常儿童分别为34例（73.9%）和18例（39.1%）；对照组分别为17例（73.9%）和10例（43.5%）。（2）随访结束时治疗组15例（32.6%）儿童出现HBeAg血清学转换。10例（21.7%）出现HBsAg清除，其中9例（19.6%）儿童HBsAg清除或伴抗-HBs转阳同时出现HBeAg血清学转换，1例（2.2%）儿童HBsAg清除，但HBeAg及抗-HBe均为阳性。对照组1例HBV DNA低于检测值下限，1例发生HBeAg血清学转换，没有发现HBsAg清除。（3）随访结束时治疗组中> 1～≤7岁患者和> 7～≤16岁患者HBeAg血清学转换率分别为45.5%和20.8%（P = 0.078）；HBsAg清除率为36.4%和8.3%（P = 0.023）。基线丙氨酸氨基转移酶水平正常和异常者HBeAg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）。儿童的性别、是否母婴传播、HBV DNA基因分型及基线HBsAg高低的抗病毒疗效比较差异均无统计学意义（P值均> 0.05）。(4)治疗24周时若HBsAg定量<3 000 IU/ml，则在随访结束时100%出现HBsAg和HBeAg清除。（5）多因素logistic回归分析结果显示HBeAg血清转换率与儿童非母婴传播及基线丙氨酸氨基转移酶异常相关；HBsAg清除率与年龄相关。 结论： 7岁以下且基线轻度丙氨酸氨基转移酶异常的免疫耐受期慢性乙型肝炎儿童干扰素序贯联合拉米夫定抗病毒治疗及延长疗程可以提高HBV DNA阴转率、HBeAg血清学转换率和HBsAg清除率。.
Keywords: Antiviral therapy; Child; Hepatitis B, chronic; Immune-tolerant.