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摘要：
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摘要：目的 探索性分析肝脏炎症2级的1～7岁慢性乙型肝炎（chronic hepatitis B，CHB）儿
童抗病毒疗效不佳的原因。方法 选取2015年1月至2018年12月在解放军总医院第五医学中
心诊断为CHB的40例1～7岁（不含7岁）儿童进行回顾性真实世界研究，所有儿童肝脏炎
症（G）为2级，经干扰素序贯恩替卡韦（小于2岁前用拉米夫定）抗病毒治疗，比较病毒
学应答组和无病毒学应答组儿童的年龄、性别、母婴阻断比例、HBV DNA定量、HBsAg
定量、HBeAg阳性比例、肝脏纤维化分期3期比例等差异。结果 ①40例儿童中获得病毒
学应答31例（77.5%），9例（22.5%）未获得病毒学应答。HBsAg转阴14例（35.0%）。
②病毒学应答组基线HBV DNA定量（中位数：7.2 lg IU/ml vs 7.9 lg IU/ml）低于无病毒学
应答组，HBeAg阳性比例 [100.0%（31/31） vs 77.8%（7/9）] 高于无病毒学应答组，差
异有统计学意义（P均＜ 0.05）。③治疗48周、72周和96周时病毒应答组患者HBV DNA
[48周：（1.7 ± 0.2）lg IU/ml vs （2.6 ± 0.5）lg IU/ml；72周：（1.3 ± 0.0）lg IU/ml vs （1.8 ±
0.3）lg IU/ml；96周：（1.3 ± 0.0）lg IU/ml vs （1.6 ± 0.2）lg IU/ml] 和HBsAg [48周：
（2.8 ± 0.8）lg IU/ml vs （3.8 ± 1.2）lg IU/ml；72周：（1.8 ± 0.4）lg IU/ml vs （3.4 ±
0.5）lg IU/ml；96周：（1.5 ± 0.3）lg IU/ml vs （3.1 ± 0.2）lg IU/ml] 水平显著低于无病
毒学应答组（P均＜ 0.05）。治疗12周 [77.8%（7/9） vs 12.9%（4/31）]、24周 [100%
（9/9） vs 25.8%（8/31）]、36周 [100%（9/9）vs 54.8%（17/31）] 无应答组患者ALT复
常率显著高于病毒学应答组，差异均有统计学意义（P均＜ 0.05）。④无病毒学应答儿
童的界面炎及汇管区炎评分较病毒应答组的Ishak评分低（中位数：0分 vs 2分），融合坏
死（中位数：2分 vs 1分）、灶性炎评分（中位数：2分 vs 1分）更高，差异有统计学意
义（P均＜ 0.05）。结论 肝脏G2级的1～7岁CHB儿童抗病毒无应答与基线时Ishak评分肝
组织界面炎轻有关，治疗12周ALT复常以及60周HBV DNA阳性可能预示疗效不佳。
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Abstract: Objective To investigate the reason of non-response to antivirus treatment in children
aged 1～7 years with chronic hepatitis B (CHB) and liver inflammation grade 2. Methods Total
of 40 children aged 1 to 7 years (excluding 7 years old) diagnosed as CHB in the Fifth Medical
Center of Chinese PLA of General Hospital from January 2015 to December 2018 were selected
for a retrospective real-world study. All children had hepatic inflammation (G) of grade 2. All
children received interferon sequential with entecavir (lamivudine before 2 years old) treatment.
The differences of age, gender, mother infant blocked ratio, HBV DNA level, HBsAg level and
proportion of stage 3 in liver fibrosis ratio between children in virological response group and non?virological response group were compared. Results ①There were 31 cases (77.5%) of all 40 children
who had virological response, and 9 cases (22.5%) had no virological response. There were 14 cases
(35.0%) with HBsAg negative. ②The baseline HBV DNA level (median: 7.2 lg IU/ml vs 7.9 lg IU/ml)
was lower, and the positive ratio of HBeAg [77.8% (7/9) vs 100.0% (40/40)] was higher of children
in virological response group than those in non-virological response group, the differences were
statistically significant (all P ＜ 0.05). ③The levels of HBV DNA [48 weeks: (1.7 ± 0.2) lg IU/ml vs
(2.6 ± 0.5) lg IU/ml; 72 weeks: (1.3 ± 0.0) lg IU/ml vs (1.8 ± 0.3）lg IU/ml; 96 weeks: (1.3 ± 0.0) lg IU/ml
vs (1.6 ± 0.2) lg IU/ml] in virological response group were significantly higher than those in non?virological response group at 48 weeks, 72 weeks and 96 weeks (all P ＜ 0.05). The rate of ALT
normalization at 12 weeks, 24 weeks and 36 weeks of children in non-virological response group
were significantly higher than those in virological response group [77.8% (7/9) vs 12.9% (4/31),
100% (9/9) vs 25.8% (8/31)，100% (9/9) vs 54.8% (17/31）], the differences were statistically
significant (all P ＜ 0.05). ④The interface inflammation and portal inflammation score with Ishak
of children in non-virological response group was significantly lower than that of virological
response group (median: 0 point vs 2 points), and the score of fusion necrosis (median: 2 points vs
1 point) and focal inflammation (median: 2 points vs 1 point) were significantly higher than those
of virological response group. Conclusions The reason of non-response with antivirus treatment in
1～7-year-old CHB children with G2 grade was related to the lower interface inflammation of liver
tissue with Ishak. The normalization of ALT at 12 weeks and HBV DNA positive at 60 weeks may
indicate the poor efficacy.
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