替比夫定在怀孕期预防乙肝病毒母婴传播疗效和安全的前瞻性和开放性研究

2012-02-25 18:48 来源:丁香园 作者:南京东南大学附属第二医院妇产科
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J Hepatol 2011 Dec;55 (6): 1215-21. [IF:9.334]  
A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection.
Han GR , Cao MK , Zhao W , Jiang HX , Wang CM , Bai SF , Yue X , Wang GJ , Tang X , Fang ZX .
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China.
南京东南大学附属第二医院妇产科

Abstract
In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200IU of HBIg within 12h postpartum and recombinant HBV vaccine of 20μg at 0, 1, and 6months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.

摘要:
在亚非地区,围产期HBV的传播是导致慢性乙型肝炎感染的主要途径。尽管应用HBV免疫球蛋白和HBV疫苗,高病毒血症母亲所生婴儿的HBV围产期传播率仍为10-30%。我们评估了替比夫定用在怀孕晚期的高病毒血症且HbeA阳性母亲身上来减少HBV传播的功效和安全性。229名HbeAg阳性且HBVDNA水平>1.0×10(7) copies/ml的母亲参加了试验。其中135名妊娠20到32周的母亲接受替比夫定600mg/d的治疗,剩余的94名作为对照组。所有的婴儿在出生后12个小时内双臂都注射200单位的乙肝免疫球蛋白,同时分别在0、1和6月时接种20ug的重组HBV疫苗。婴儿28周时,根据HBsAg 和HBV DNA的结果来确定围产期的传播率。所有接受替比夫定治疗的个体都在抗逆转录酶药物妊娠登记处注册。替比夫定治疗与血清中HBV DNA和HbeAg水平的显著降低以及生产之前升高的ALT水平恢复正常存在相关性。治疗开始至第四周,HBV DNA水平显著降低,且自十二周开始保持在低水平。接受替比夫定治疗的135名母亲中的44名(33%)和所有对照组中的母亲在生产时都没有PCR可测的病毒血症(DNA<500 copies/ml)。生产后7个月,经过对婴儿的完整随访,接受替比夫定治疗的母亲所生孩子的围产期传播发生率要低于对照组(0% vs. 8%; p=0.002)。HBV DNA水平只有在HbsAg阳性的婴儿身上才能检测到。出生后随访过程中,乙肝表面抗体的水平没有显著性差异。接受治疗的母亲和她们的婴幼儿身上也没有观测到严重的副作用。在慢性乙型肝炎、HbeAg阳性且高病毒血症的母亲怀孕期间应用替比夫定可以安全地降低围产期HBV传播。通过短期随访可知,接受替比夫定治疗的母亲和她们的婴幼儿可以良好地耐受此药,且无安全方面的担忧。以上数据可以支持替比夫定在这一特定人群中的应用。

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