替比夫定阻断乙型肝炎病毒母婴传播停药后的安全性研究

The safety of telbivudine in preventing mother-to-infant transmission of hepatitis B virus in pregnant women after discontinuation

目的观察替比夫定阻断HBVDNA高载量孕妇宫内传播的效果及停药后的安全性。方法收集慢胜HBV携带者且孕周24～30周孕妇资料，HBVDNA均≥1×10^6IU／ml；根据患者意愿将其分为“替比夫定治疗组”和“对照组”，替比夫定治疗组在孕妇孕26周时，给予替比夫定600mg／d口服抗病毒治疗至产后1个月停用，对照组患者不用抗病毒药物。两组孕妇均接受剖宫产术，新生儿产后均接受主、被动联合免疫，出生后12h内注射乙型肝炎免疫球蛋白200IU及0、1、6个月注射乙型肝炎疫苗20μg。禁止母乳喂养。计量资料比较用t检验，计数资料比较用x^2检验。结果共收集157例HBV携带者孕妇资料，替比夫定治疗组82例，对照组75例，年龄20～40岁。替比夫定治疗组孕妇HBVDNA在产前下降均〉2log10有效率为100％，至分娩前替比夫定治疗组有16例HBV DNA转阴，转阴率为19．5％（16／82），而对照组无转阴，两组比较，差异有统计学意义护〈0．05）。两组新生儿及随访婴儿至6个月，替比夫定治疗组婴儿HBsAg、HBVDNA阳性率均为0，对照组婴儿HBsAg、HBVDNA阳性率均为5．3％，替比夫定治疗组与对照组HBV母婴传播的阻断率分别为100％和94．7％，两组比较，差异均有统计学意义护值均〈0．05）。替比夫定治疗组停药后随访至产后6个月，HBVDNA：（1．79×10^7±4．20×10^7）IU／ml，ALT：（31．72±9．89）U／L，AST：（31．49±9．93）U／L。两组均未发现有不良反应或先天胜畸形。结论HBVDNA高滴度孕妇妊娠中晚期应用替比夫定抗病毒治疗能明显降低孕妇外周血HBVDNA载量，阻断HBV宫内传播，且近期疗效、耐受性和安全眭良好。肝生物化学指标正常孕妇短程服用替比夫定停药后安全性好。

Objective To determine the efficacy and safety of telbivudine for blocking intrauterine transmission of hepatitis B virus （HBV） in pregnant women with high-load HBV DNA. Methods Women in general good health and pragnant were enrolled for study between the ages of 20 to 40 year-old, with a diagnosis of HBV infection with high-load HBV DNA level （ ≥ 1 × 10^6IU / ml）. According to each participant＇s willingness, the women were divided into a telbivudine treatment group （82 women） and an untreated control group （75 women）. The telbivudine treatment was initiated at gestation week 26 as oral dosing of 600 mg/d and continued until 1 month after the birth. Women in the control group had not gotten any antiviral drug treatment. All of the women delivered by cesarean section, and all of the neonates were administered the standard passive immunization therapy, which consisted of a hepatitis B immunoglobulin （200 IU） injection given within 12 hours of birth and an injection of hepatitis B vaccine （20 txg） at birth and at postnatal month 1 and 6. None of the mother＇s performed breastfeeding. Results The telbivudine-treated women showed a significant decrease in HBV DNA levels prior to delivery, as well as significantly decreased prenatal HBV DNA levels （〉2 logl0）. Efficiency of the telbivudine treatment was 100%. Immediately prior to delivery, 16 （19.5%） of the women in the telbivudine treatment group showed negative HBV DNA status, as opposed to the untreated control group in which no women showed negative status. The telbivudine treatment group had no case of maternal or fetal adverse reaction or of congenital malf ormation. Conclusion Use of telbivudine antiviral therapy during late pregnancy in women with high-load HBV DNA can significantly reduce level of HBV DNA in maternal peripheral blood, block HBV intrauterine transmission, and provide good short-term efficacy, with good tolerability and safety.