HBV感染免疫耐受期孕妇应用替比夫定阻断母婴传播有效性及停药安全性的研究

Telbivudine for prevention of perinatal transmission in pregnant women infected with hepatitis B virus in immune-tolerant phase： a study of efficacy and safety of drug withdrawal

目的HBV感染免疫耐受期高病毒血症孕妇妊娠中晚期应用替比夫定（LdT）治疗，观察母婴阻断成功率，治疗期间及停药后丙氨酸氨基转移酶（ALT）升高的比例，评价母婴阻断有效性及孕妇的安全性。方法HBV感染免疫耐受期即ALT正常（≤40U／L），HBeAg阳性且高病毒载量（HBVDNA≥6log10IU／ml）孕妇，在妊娠中晚期应用LdT抗病毒治疗阻断HBV母婴传播。所有婴儿给予标准联合免疫。若婴儿7个月（或第三针乙型肝炎疫苗注射后1个月）HBsAg阳性或HBVDNA阳性则定义为HBV母婴阻断失败。检测孕妇在基线、治疗1个月、分娩前及停药后1、3、6个月肝功能、HBVDNA及HBV血清标志物定量值。数据分析应用SPSS软件16．0，计量资料的组间比较应用t检验，计数资料的组间比较应用疋。检验。结果104例孕妇接受LBT600mg每日1次口服治疗（治疗组），25例孕妇未接受抗病毒治疗（观察组）。治疗组及观察组母婴阻断成功率分别为100％、89．47％（x2=9．862，P=0．028），差异有统计学意义。在治疗过程中及停药后6个月内，治疗组患者中有5例发生AIJT升高（5／104，4．81％），观察组患者中ALIT升高1例（1／25，4．00％）（x2=0．030，P=1．000），差异无统计学意义。治疗组患者基线HBVDNA平均值为（8．20±0．78）log10IU／ml;分娩前HBVDNA平均值下降至（3,98±0．90）log10IU／ml（f=6．979，P〈0．001），差异有统计学意义。100例停药患者在分娩后1个月HBVDNA反弹至（8．11±O．80）log10IU／ml。结论免疫耐受期高病毒血症孕妇在妊娠中晚期应用LdT治疗可有效降低HBV母婴传播率。母亲在分娩后立即停药是安全的，停药后肝炎发作的比例低。

Objective To observe the success rate of telbivudine （LdT） for the prevention of perinatal transmission of hepatitis B virus （HBV） and the incidence of alanine aminotransferase （ALT） elevation during LdT treatment and after LdT withdrawal in HBV-infected pregnant woman with high viremia in immune-tolerant phase and receiving LdT treatment at the end of pregnancy, and to evaluate the efficacy of LdT in the prevention of perinatal transmission and the safety for pregnant women. Methods Pregnant women infected with HBV in immune-tolerant phase who had normal ALT levels （ ≤ 40 U/L） and high viremia （HBV DNA ≥ 6 log10 IU/ml） with positive HBeAg were enrolled as subjects. All pregnant women received antiviral treatment with LdT at the end of pregnancy to prevent perinatal transmission of HBV. All infants received standard combined immunoprophylaxis. Failure for prevention of perinatal transmission of HBV was defined as positive HBsAg or HBV DNA in infants 7 months of age （or at one month after the third injection of hepatitis B vaccine）. Liver function, HBV DNA, and HBV serological markers were evaluated at baseline, after 1 month of treatment, before childbirth, and 1, 3, and 6 months after drug withdrawal. SPSS 16.0 software was used to analyze the data. Between-group comparison of continuous data was made by t test, and comparison of categorical data was made by chi-square test. Results One hundred and four pregnant women （treatment group） received oral administration of 600 mg LdT once a day, and 25 pregnant women （observation group） did not receive any antiviral therapy. The success rate for the prevention of perinatal transmission was significantly higher in the treatment group than in the observation group （100% vs 89.47%,x2 = 9.862,P = 0.028）. There was no significant difference in the incidence of ALT elevation during treatment and within 6 months after drug withdrawal between the treatment group and the observation group （4.81% （5/104） vs 4.00% （1/25）,x 2 = 0.030, P = 1.000）. In the treatment group, the mean HBV DNA at baseline was significantly higher than that before childbirth （8.20±0.78 vs 3.98±0.90 log10IU/ml, t = 6.979,P 〈 0.001）. One hundred patients with drug withdrawal had HBV DNA increased to 8.11±0.80 log10 IU/ml at one month after childbirth. Conclusion LdT treatment at the end of pregnancy can effectively reduce the incidence of perinatal transmission of HBV in pregnant women with high viremia in immune-tolerant phase. The immediate drug withdrawal after childbirth is safe for the mother. The incidence of hepatitis is low after drug withdrawal.