乙型肝炎病毒变异在母婴传播中的初步研究

目的 探索肝细胞癌相关乙肝病毒变异在母婴传播和婴儿慢性感染中变化规律,为肝细胞癌的防控提供理论支撑。方法 将413名HBV表面抗原(HBsAg)阳性产妇及其新生儿纳入本研究。应用定量PCR检测产妇外周血和新生儿脐带血HBV DNA,应用套式PCR和克隆测序方法测定前S区和核心启动子区的HCC相关HBV变异。出生经标准HBV免疫,7个月后对104名婴儿HBV感染情况进行成功随访,对外周血HBV DNA阳性婴儿测定HCC相关HBV变异发生情况。结果 在413名新生儿中,41名(9.9%)新生儿HBV DNA水平≥10₃ copies/mL。随访到104名婴儿中,4名(占3.8%)HBV DNA≥10₃ copies/mL。与未发生HBV跨胎盘传播的产妇相比,发生HBV跨胎盘传播者外周血HBV核心启动子变异没有增加,但在C2基因亚型的前S区中,T2898G/C, C3000T, C3116T, T31C和T52C变异显著增加HBV跨胎盘传播的风险。HBV基因组中前S区和核心启动子区的HCC相关变异的频率在产妇外周血和新生儿脐带血中无明显差别,但是在母婴传播的7月龄HBV DNA阳性婴儿中,这些变异几乎不存在。结论 HBV C2基因亚型的前S区某些变异可能影响HBV跨胎盘传播,但是HCC相关HBV变异准种并没有造成婴儿慢性感染的优势,促进HBV致癌的变异体是在漫长的慢性感染过程中逐渐被选择出来的。

Hepatitis B virus mutations during mother-to-children transmission: a preliminary study

Objective To explore the mutations of hepatocellular carcinoma (HCC)-related hepatitis B virus (HBV) during mother-to-child transmission, so as to provide theoretic evidence for prophylaxis of HCC from the very beginning. Methods A total of 413 HBsAg-positive mothers and their newborns were enrolled in this study. Serum HBV DNA levels in maternal peripheral blood and cord blood of the newborns were measured using real-time quantitative PCR. Nested PCR together with cloning and sequencing methods were applied to examine the HCC-related HBV mutations in the preS and basal core promoter regions of HBV genome. All the newborns received standard HBV vaccination. Of the 413 newborns, 104 were successfully followed-up 7 months after birth, and the HBV mutations were examined if their circulating HBV DNA was detectable. Results Of the 413 newborns, 41 (9.9%) had HBV DNA level >10³ copies/mL in their cord blood. Four (3.8%) of the 104 newborns who were successfully followed up had circulating HBV DNA level >10³ copies/mL 7 months after birth. Compared to mothers without HBV trans-placental transmission, those with HBV trans-placental transmission had no increase in HBV mutations in the basal core promoter region. However, the viral mutations containing T2898G/C, C3000T, C3116T, T31C, and T52C in the preS region of HBV subgenotype C2 significantly increased the risk of HBV trans-placental transmission (P <0.05). The frequencies of the HCC-related mutations in the preS and basal core promoter regions of HBV genome were not significantly different between maternal peripheral blood and the cord blood of the newborns. Importantly, the HCC-related mutations were rarely found in the HBV-positive infants at 7 months after birth. Conclusion The HBV mutations in the preS region of HBV subgenotype C2 may affect the trans-placental transmission of HBV. However, the quasispecies of HCC-related HBV mutants have no advantage in causing chronic HBV infection in infants. The HBV mutants which can promote HCC are selected during the long term chronic infection.