Chen Chuanying, Tu Xianglin, Cheng Quanhong, Chen Fang, Dai Ying, Gong Fanghua, Lin Xue
The Affiliated Infectious Hospital, Nanchang University, Nanchang 330002, China.
Zhonghua Gan Zang Bing Za Zhi. 2015 Jan;23(1):9-12. doi: 10.3760/cma.j.issn.1007-3418.2015.01.004.
To explore the antiviral efficacy, safety and protective ability against mother-to-infant transmission of telbivudine in pregnant patients with chronic hepatitis B (CHB) during the first trimester.
Eighty four gravid women who were diagnosed with CHB, in their first trimester of pregnancy, and had refused to terminate their pregnancies were enrolled; all study participants were clinically classified as active hepatitis cases with positivity for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), HBV DNA more than or equal to 107 copies/mL and serum level of alanine aminotarnsferase (ALT) of more than or equal to 4 ULN.Patients with YMDD mutations were excluded from the study. The study participants were divided into a telbivudine treatment group (n=43; administered in the first trimester of pregnancy) and a control group (n=41, consisting of patients who refused to take antivirals). All babies bom to the women in both groups of the study received standard immune prevention (anti-hepatitis B immunoglobulin plus hepatitis B vaccine) and artificial feeding.Data recorded for the women during pregnancy included clinical findings for tests of hepatic and renal function, myocardial enzymes, blood and urine clinical parameters, hepatitis B virus makers and HBV DNA, as well as notation of any adverse reactions. The neonates were evaluated for presence of HBV infection, parameters of growth and development, presence of complications, and Apgar score. At 6 and 12 months old, all infants were evaluated for HBV DNA level and HBsAg presence.
The genetic variant rtM204I was detected in one of the women in the treatment group at 36 weeks of pregnancy. One woman in the control group developed severe hepatitis at 28 weeks of pregnancy and was put on the telbivudine treatment The treatment group showed greater recovery rates of ALT than the control group at 12 weeks of pregnancy (62.8% vs.29.3%, P=0.002), 24 weeks of pregnancy (76.7% vs.46.3%, P=0.000), and at ante partum (88.1% vs.60.0%, P=0.004). The treatment group also showed greater HBV DNA-negative conversion rates at 12 weeks of pregnancy (20.9% vs.0, P=0.006), at 24 weeks of pregnancy (37.2% vs.0, P=0.001) and at ante partum (78.6% vs.0, P=0.000), and greater HBeAg seroconversion rates at 12 weeks of pregnancy (2.3% vs.0, P=1.000), at 24 weeks of pregnancy (9.3% vs.0, P=0.116) and at ante partum (2 1.4% vs.0, P=0.002). The HBsAg-positive rates and HBV DNA-positive rates among the infants born to the mothers in the treatment and control groups, respectively, were 2.4% vs.17.5% (P=0.027) at birth, 0 vs.17.5% (P=0.005)at 6 months old and 0 vs.17.5% (P=0.005) at 12 months old. The Apgar scores were not significantly different for the children born to the mothers from the two groups, and all the children showed parameters of growth development within normal limits.
Telbivudine administration in the first trimester had a good antiviral curative effect and effectively blocked mother-to-infant transmission in women with CHB. The treatment was safe, causing no obvious adverse reaction in the gravid women or developmental effects on the infants.
探讨替比夫定对孕早期慢性乙型肝炎（CHB）孕妇的抗病毒疗效、安全性及母婴传播阻断能力。
纳入84例孕早期诊断为CHB且拒绝终止妊娠的孕妇；所有研究参与者临床分类为活动性肝炎病例，乙肝表面抗原（HBsAg）和乙肝e抗原（HBeAg）均为阳性，HBV DNA≥107拷贝/mL，血清丙氨酸氨基转移酶（ALT）水平≥4倍正常上限。排除YMDD突变患者。研究参与者分为替比夫定治疗组（n = 43；于孕早期给药）和对照组（n = 41，由拒绝服用抗病毒药物的患者组成）。两组孕妇所生婴儿均接受标准免疫预防（乙肝免疫球蛋白加乙肝疫苗）及人工喂养。记录孕妇孕期的肝功能、肾功能、心肌酶、血液及尿液临床参数、乙肝病毒标志物和HBV DNA检测结果，以及任何不良反应。评估新生儿的HBV感染情况、生长发育参数、并发症情况及Apgar评分。在婴儿6个月和12个月时，评估其HBV DNA水平及HBsAg情况。
治疗组1例孕妇在孕36周时检测到rtM204I基因变异。对照组1例孕妇在孕28周时发生重型肝炎，开始接受替比夫定治疗。治疗组在孕12周（62.8%对29.3%，P = 0.002）、孕24周（76.7%对46.3%，P = 0.000）及产前（88.1%对60.0%，P = 0.004）时ALT恢复率高于对照组。治疗组在孕12周（20.9%对0，P = 0.006）、孕24周（37.2%对0，P = 0.001）及产前（78.6%对0，P = 0.000）时HBV DNA阴转率更高，在孕12周（2.3%对0，P = 1.000）、孕24周（9.3%对0，P = 0.116）及产前（21.4%对0，P = 0.002）时HBeAg血清学转换率更高。治疗组和对照组母亲所生婴儿出生时HBsAg阳性率及HBV DNA阳性率分别为2.4%对17.5%（P = 0.027），6个月时为0对17.5%（P = 0.005），12个月时为0对17.5%（P = 0.005）。两组母亲所生儿童的Apgar评分无显著差异，所有儿童生长发育参数均在正常范围内。
孕早期应用替比夫定具有良好的抗病毒疗效，可有效阻断CHB孕妇的母婴传播。该治疗安全，对孕妇无明显不良反应，对婴儿无发育影响。
