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孕中期与孕晚期使用拉米夫定预防慢性乙型肝炎母婴传播的研究

Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B.

作者信息

Pan C Q, Yi W, Liu M, Wan G, Hu Y-H, Zhou M-F

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Medical Center, New York University School of Medicine, New York, NY, USA.

Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

出版信息

J Viral Hepat. 2017 Mar;24(3):246-252. doi: 10.1111/jvh.12640. Epub 2016 Dec 26.

Abstract

There are little data on the timing of initiating lamivudine therapy for preventing transmission of hepatitis B in highly viremic mothers. Between May 2008 and January 2015, we retrospectively enrolled mothers with HBV DNA >6 log  copies/mL who received lamivudine during pregnancy, and we compared them to untreated mothers. The primary measurement was the vertical transmission rate. The secondary outcomes were the mothers' and infants' safety. Among 249 consecutive mothers enrolled, 66 and 94 received lamivudine during the second and third trimesters, respectively, and 89 were untreated. At delivery, maternal mean HBV DNA levels were significantly lower in mothers who received lamivudine (4.45 log vs 7.16 log  copies/mL; P<.001). Lamivudine treatment was well tolerated. However, early treatment during the second trimester did not significantly increase the percentage of mothers achieving HBV DNA levels of <6 log  copies/mL compared to those treated during the third trimester (98.5% vs 94.7%; P=.40). At the age of 28 weeks, the vertical transmission rates were significantly lower in the lamivudine-treated mothers vs in the untreated mothers (0% [0/160] vs 5.62% [5/89]; P<.001), but the rates were similar when comparing the two subgroups treated with lamivudine (0% [0/66] vs 0% [0/94], P>.05). The birth defect rates and mothers' and infants' adverse events were similar among the groups. Lamivudine treatment initiated in the second or third trimester for mothers with HBV DNA levels below 9 log  copies/mL was equally safe and effective in preventing vertical transmission. Thus, lamivudine should be deferred until the third trimester to minimize foetal exposure and drug resistance.

摘要

关于在高病毒血症母亲中启动拉米夫定治疗以预防乙型肝炎传播的时机,相关数据较少。在2008年5月至2015年1月期间,我们回顾性纳入了孕期接受拉米夫定治疗且HBV DNA>6 log拷贝/mL的母亲,并将她们与未治疗的母亲进行比较。主要测量指标是垂直传播率。次要结局是母亲和婴儿的安全性。在连续纳入的249名母亲中,分别有66名和94名在孕中期和孕晚期接受了拉米夫定治疗,89名未接受治疗。分娩时,接受拉米夫定治疗的母亲的母体平均HBV DNA水平显著较低(4.45 log对7.16 log拷贝/mL;P<0.001)。拉米夫定治疗耐受性良好。然而,与孕晚期接受治疗的母亲相比,孕中期早期治疗并未显著增加实现HBV DNA水平<6 log拷贝/mL的母亲百分比(98.5%对94.7%;P=0.40)。在28周龄时,接受拉米夫定治疗的母亲的垂直传播率显著低于未治疗的母亲(0%[0/160]对5.62%[5/89];P<0.001),但比较两个接受拉米夫定治疗的亚组时,传播率相似(0%[0/66]对0%[0/94],P>0.05)。各组间出生缺陷率以及母亲和婴儿的不良事件相似。对于HBV DNA水平低于9 log拷贝/mL的母亲,在孕中期或孕晚期开始拉米夫定治疗在预防垂直传播方面同样安全有效。因此,拉米夫定应推迟至孕晚期,以尽量减少胎儿暴露和耐药性。

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