Departments of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
Medical Education and Bioethics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
Hepatology. 2015 Aug;62(2):375-86. doi: 10.1002/hep.27837. Epub 2015 May 13.
The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines.
Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.
本研究旨在评估替诺福韦酯（TDF）治疗对降低母婴乙型肝炎病毒（HBV）传播的疗效和安全性。
我们进行了一项前瞻性、多中心试验，纳入了 118 例 HBsAg 和 HBeAg 阳性、HBV DNA≥7.5 log10 IU/mL 的妊娠妇女。母亲在妊娠 30-32 周时开始接受 TDF（TDF 组，n=62）或不接受药物治疗（对照组，n=56），直至产后 1 个月。主要终点为婴儿 6 个月时的 HBsAg 阳性率。
与对照组相比，TDF 组在分娩时的 HBV DNA 水平更低（4.29±0.93 对数 10 IU/mL vs 8.10±0.56 对数 10 IU/mL，P<0.0001）。在 121/123 名新生儿中，TDF 组的 HBV DNA 阳性率（6.15% vs 31.48%，P=0.0003）和 HBsAg 阳性率（1.54% vs 10.71%，P=0.0481）更低。多因素分析显示，TDF 组的婴儿 HBsAg 阳性风险更低（比值比=0.10，P=0.0434），而羊膜穿刺术与婴儿 HBsAg 阳性风险增加相关（比值比=6.82，P=0.0220）。TDF 组的母亲丙氨酸氨基转移酶（ALT）水平高于正常上限两倍且持续时间≥3 个月的发生率较低（3.23% vs 14.29%，P=0.0455），产后 ALT 升高程度较轻（P=0.007），ALT 高于正常上限 5 倍的发生率较低（1.64% vs 14.29%，P=0.0135）。两组的母亲血肌酐和肌酸激酶水平、先天性异常、早产和婴儿生长参数均相似。在 12 个月时，1 例 TDF 组婴儿新出现 HBsAg 阳性，可能是由于产后感染和疫苗产生的体液免疫应答不足所致。
TDF 治疗高病毒血症的母亲可降低婴儿出生时的 HBV DNA 水平和 6 个月时的 HBsAg 阳性率，并改善母亲的 ALT 升高。
