乙型肝炎病毒感染孕妇孕期及产后病毒载量与抗原表达的动态变化

Dynamic changes of viral load and antigen expression in hepatitis B virus-infected pregnant women during and after pregnancy

目的：探讨妊娠对乙型肝炎病毒（HBV）感染孕妇病毒复制及抗原表达的影响。方法：选取2008年9月-2014年3月孕前肝功能正常的371例乙型肝炎表面抗原（HBsAg）阳性孕妇为研究对象,本研究共有5个不同的采血时期,分别为孕中期（孕25-28周）、分娩时（分娩前后各2天）、产后6-8周、产后7-12个月及远期随访〔平均（4.8±1.1）年〕,每例孕妇至少观察两个时间点。采用酶联免疫吸附测定（ELISA）法检测HBV血清学标志,采用实时荧光定量PCR法检测HBV DNA水平,应用S基因测序确定病毒基因型。结果：371例孕妇中,34例乙型肝炎e抗原（HBeAg）阳性孕妇在孕期或产后出现谷丙转氨酶（ALT）升高;孕中期或分娩时HBV DNA水平及HBsAg浓度与产后7-12个月比较,差异均无统计学意义（P〉0.05）,仅HBeAg浓度在产后7-12个月有所降低（P〈0.05）。337例ALT正常者中,77例孕中期HBeAg阳性孕妇及其产后7-12个月的HBV DNA均为7.94 log IU/ml,HBsAg分别为4.54 log IU/ml和4.61 log IU/ml,HBeAg分别为3.10 log S/CO和3.09 log S/CO（P〉0.05）。70例分娩时HBeAg阳性孕妇及其产后7-12个月的HBV DNA分别为7.73 log IU/ml和7.98 log IU/ml,HBsAg分别为4.46 log IU/ml和4.59 log IU/ml,HBeAg分别为3.09 log S/CO和3.08 log S/CO（P〉0.05）。173例HBsAg阳性孕妇孕中期与远期随访比较,其中HBeAg阳性28例,HBV DNA分别为8.06 log IU/ml和7.95 log IU/ml（P=0.973）,HBsAg分别为4.82 log IU/ml和4.79 log IU/ml（P=0.062）,HBeAg分别为2.96 log S/CO和2.94 log S/CO（P=0.414）;另145例HBeAg阴性孕妇孕中期与远期随访比较,其中HBV DNA分别为2.62 log IU/ml和2.82 log IU/ml（P=0.171）,HBsAg分别为3.45 log IU/ml和3.44 log IU/ml（P=0.055）。此外,对17例肝功能正常孕妇孕中期、分娩时、产后6-8周及产后7-12个月的动态观察结果显示：其HBV DNA水平在不同时期均无明显波动,HBsAg及HBeAg浓度也无明显变化（P〉0.05）。结论：不论肝功能正常与否,HBsAg阳性孕妇在不同孕期及产后时期,血清中HBV DNA水平和病毒抗原浓度均无明显变化,说明妊娠对HBV感染者体内病毒复制以及抗原表达无显著影响。

Objective： To explore the effect of pregnancy on viral replication and antigen expression in hepatitis B virus （HBV） - infected pregnant women during and after pregnancy. Methods： A total of 371 HBsAg-positive pregnant women with normal liver function before pregnancy were selected from September 2008 to March 2014 as study respondents, blood collection was performed during the second trimester of pregnancy （25-28 gestational weeks）, at the time of birth （2 days before and after delivery）, at 6-8 weeks after delivery, at 7 -12 months after delivery, and during follow-up （4. 8±1.1 years on average）. Each pregnant woman was observed at least at two time points. ELISA was used to detect HBV serological indexes, real-time fluorescent quantitative PCR was used to detect HBV DNA levels, S gene sequencing was used to determine the genotypes. Results：Among 371 pregnant women, 34 HBeAg-positive women were found with high alanine transaminase （ALT） during or after pregnancy; there was so statistically significant difference in HBV DNA level and HBsAg concentration between the second trimester of pregnancy, at the time of birth and at 7-12 months after delivery （P〉0. 05 ） , only HBeAg concentration decreased at 7-12 months after delivery （P〈0. 05 ）. Among 337 pregnant women with normal ALT levels, HBV DNA levels of 77 HBeAg-positive pregnant women during the second trimester of pregnancy and at 7-12 months after deliverywere 7.94 log IU/ml, HBsAg levels were 4. 54 log IU/ml and 4. 61 log IU/ml, respectively, HBeAg levels were 3.：10 log S/CO and 3.09 log S/CO, respectively, there were statistically significant differences （P〉0. 05 ）. HBV DNA levels of 70 HBeAg-positive pregnant women at the time of birth and at 7-12 months after delivery were 7.73 log IU/ml and 7.98 log IU/ml, respectively, HBsAg levels were 4. 46 log IU/ml and 4. 59 log IU/ml, respectively, HBeAg levels were 3.09 log S/CO and 3.08 log S/CO, respectively, there were statistically significant differences （P〉0. 05）. Among 173 HBsAg-positive pregnant women, 28 pregnant wemen were found with positive HBeAg, HBV DNA levels during the second trimester of pregnancy and long-term follow-up were 8.06log IU/ml and 7. 95 log IU/ml, respectively （P= 0. 973 ）, HBsAg levels were 4. 82 log IU/ml and 4. 79 log IU/ml, respectively （P=0. 062）, HBeAg levels were 2. 96 log S/CO and 2. 94 log S/CO, respectively （P=0.414）; the other 145 pregnant women were found with negative HBeAg, HBV DNA levels during the second triwesteI of pregnancy and long-term follow-up were 2. 62 log IU/ml and 2. 82 log IU/ml, respectively （ P = 0. 171 ）, HBsAg levels were 3. 45 log IU/ml and 3.44 log IU/ml, respectively （ P = 0. 055 ） . In addition, dynamic observation showed that HBV DNA levels did not change significantly during different periods, HBsAg and HBeAg levels did not change significantly （P〉0. 05） . Conclusion： Serum HBV DNA level and viral antigen concentrations among HBsAg-positive pregnant women with normal and abnormal liver function show no significant change during different periods of pregnancy and after delivery, the results demonstrate that pregnancy has no significant impact on viral replication and antigen expression of HBV-infeeted pregnant women.