妊娠后期拉米夫定抗病毒治疗HBV DNA高载量孕妇的母婴结局分析

Maternal-fetal outcomes of lamivudine treatment administered during late pregnancy to highly viremic mothers with HBeAg＋ chronic hepatitis B

目的评价HBV DNA高载量孕妇妊娠后期拉米夫定抗病毒治疗的有效陛、安全性及相关母婴结局。方法选择HBV DNA〉1×10^6拷贝／ml且于妊娠20～34周口服拉米夫定孕妇164例，选择同期未治疗孕妇92例为对照组。所有婴儿出生后接受主、被动联合免疫，观察至7月龄。统计两组孕妇治疗前及分娩前HBV DNA水平、HBV标志物、肝肾功能和血常规，及婴儿出生时、1月龄、7月龄的HBV标志物，比较分析拉米夫定治疗的HBV母婴传播率、治疗应答率、肝功能复常率、不良反应、妊娠合并症及婴儿畸形、发育隋况。计量资料数据组间比较用t检验，计数资料组间比较采用χ^2检验或者Fisher＇s精确概率法。结果拉米夫定组160例孕妇分娩前HBVDNA下降对数值〉2log10拷贝／ml，治疗应答率达97．56％（160／164）；分娩前拉米夫定组的HBV DNA水平为（3．72±1．78）log10拷贝／ml，明显低于对照组（7．83±0．67）log10拷贝／ml，t=-22．359，P〈0．01。拉米夫定组分娩前肝功能复常率为90．20％，明显高于对照组的55．88％（χ^2=13．349，P〈0．01）；HBeAg滴度为（957．73±458．42）S／CO，显著低于对照组的（1296．35±383．14）S／CO，t=-5．410，P〈0．01。出生时，拉米夫定组与对照组婴儿HBV母婴垂直传播率分别为15．24％（25／164）和30．43％（28／92）；随访至7月龄，两组婴儿母婴垂直传播率分别为0和8．％（8／92），χ^2=14．721，P〈0．01。拉米夫定组无一例患者因不能耐受拉米夫定而中途退出，也无一例婴儿发生先天畸形。两组在产后出血、孕龄、婴儿陛别比、婴儿体质量及apgar评分方面的差异无统计学意义。结论妊娠后期口服拉米夫定能明显降低HBV母婴垂直传播率，促进孕妇肝功能复常，且近期安全陛尚可。

Objective To evaluate the therapeutic efficacy and safety of lamivudine treatment in late pregnancy by analyzing the maternal-fetal outcomes of chronic hepatitis B （CHB） mothers featuring hepatitis B e antigen （HBeAg）-positivity and highly viremic status. Methods A total of 256 pregnant women in the second or third trimester with monoinfected CHB, HBeAg-positivity, and HBV DNA 〉 6 log10 copies/mL were divided into two groups： lamivudine （lam） treatment （n = 164） or no treatment （controls; n = 92）. All infants were treated with hepatitis B immune globin （HBIg; 200 IU） within 12 hrs of birth and 15 days later, and were given the recombinant HBV vaccine （20 Ixg） at 0, 1 and 6 months. All infants were followed-up to at least seven months and hepatitis B surface antigen （HBsAg） and HBV DNA levels were used to determine perinalal transmission （PT） rates. The mothers＇ data from routine blood analysis, tests of hepatic and renal function, detection of HBV markers and HBV DNA were retrospectively analyzed to determine changes associated with the lain treatment. Correlations of lam treatment with HBV PT rate, alanine aminotransferase （ALT） normalization, adverse reactions, pregnancy complications, congenital deformities, and infants＇ growth/ development were determined by statistical analyses. Results Prior to delivery, the lam-treated mothers had significantly lower HBV DNA levels （3.72 ± 1.78 vs. controls： 7.83 ± 0.67 log10 c/ml; t=-22.359, P〈 0.001）. The rate of virological response in the lam-treated group was 97.56% （160/164）. The lam-treated group had significantly higher ALT normalization rate （90.20% vs. controls： 55.88%; χ^2 = 13.349, P〈0.001） and significantly lower HBeAg titer （957.73 ±458.42 vs. controls： 1296.35 ± 383.14 S/CO; t=-5.410, P〈 0.001）. At birth, the infants from lain-treated mothers had significantly lower HBsAg-positivity （15.24% （25/164） vs. controls： 30.43% （28/92）; χ^2 = 8.284, P= 0.004）. By 7-12 months after birth, none of the infants born to lamtreated mothers tested positive for HBsAg, compared to 8.70% （8/92） of the infants born to mothers in the control group （χ^2= 14.721,P〈0.001）. None of the lam-treated mothers required treatment discontinuation due to adverse events or lam-resistance. No congenital deformities were observed during the study and follow-up periods. There were no differences between the lam-treated and control groups for postpartum hemorrhage, gestational age, infants＇ height/weight or Apgar scores. Conclusion In highly viremic HBsAg＋ mothers with CHB, lam treatment in the second or third trimester of pregnancy is safe and effective for reducing HBV maternal-neonatal transmission.