HBV感染合并ICP孕妇胎盘ABCB4 mRNA表达与妊娠结局的关系

Association between placental ABCB4 mRNA expression and pregnancy outcomes in pregnant women with HBV infection complicated by ICP

摘要

目的 分析乙型肝炎病毒(HBV)感染合并妊娠期肝内胆汁淤积症(ICP)孕妇的胎盘三磷酸腺苷结合盒转运子B亚族成员4(ABCB4) mRNA表达水平,并探讨ABCB4 mRNA表达与妊娠结局的关系。方法 选取金华市中心医院、金华市妇幼保健院自2021年1月至2024年6月收治的82例慢性HBV感染孕妇为研究对象,其中52例单纯HBV感染孕妇纳入HBV组,30例合并ICP孕妇纳入HBV合并ICP组。另筛选同期同院因社会因素剖宫产并留取胎盘组织的30例正常孕妇作为对照组。逆转录-聚合酶链反应(RT-PCR)检测胎盘ABCB4 mRNA表达,比较三组孕妇胎盘ABCB4 mRNA表达水平;Logistic回归分析ABCB4 mRNA表达水平与慢性HBV感染孕妇妊娠结局的关系。结果 对照组、HBV组、HBV合并ICP组胎盘ABCB4 mRNA表达水平依次降低,差异有统计学意义(Z=83.071,P<0.001);HBV合并ICP组患者中,重度ICP患者ABCB4 mRNA表达低于轻度ICP,差异有统计学意义(Z=3.683、P<0.001);HBV合并ICP组不良妊娠结局总发生率高于HBV组,差异有统计学意义(χ²=4.852,P<0.05);妊娠结局不良组胎盘ABCB4 mRNA表达低于妊娠结局良好组,差异有统计学意义(t=8.541、P<0.001);妊娠结局不良组合并ICP患者比例及血清总胆汁酸(TBA)、谷草转氨酶(AST)、总胆红素水平均高于妊娠结局良好组,差异有统计学意义(χ²/Z/t值介于4.012~19.404之间,P<0.05);多因素Logistic回归分析结果显示,胎盘ABCB4 mRNA高表达为慢性HBV患者不良妊娠结局的保护因素,合并ICP、高水平AST是危险因素,其OR值及95%CI分别为0.463(0.303~0.706)、3.196(1.081~9.449)、1.149(1.067~1.238)。结论 与慢性HBV感染孕妇相比,合并ICP的孕妇具有更低的胎盘ABCB4 mRNA表达,不良妊娠结局风险更高,值得临床重视。

Abstract

Objective To analyze the placental expression level of ATP-binding cassette subfamily B member 4 (ABCB4) mRNA in pregnant women with hepatitis B virus (HBV) infection complicated by intrahepatic cholestasis of pregnancy (ICP), and to explore the relationship between ABCB4 mRNA expression and pregnancy outcomes. Methods A total of 82 pregnant women with chronic HBV infection who were admitted to Jinhua Municipal Central Hospital and Jinhua Maternal and Child Health Care Hospital from January 2021 to June 2024 were selected as the research subjects. Among them, 52 pregnant women with simple HBV infection were included in the HBV group, while 30 women with HBV and ICP were included in the HBV with ICP group. An additional 30 healthy pregnant women who underwent cesarean section due to social reasons and had placental tissues collected during the same period served as the control group. Placental ABCB4 mRNA expression was detected using reverse transcription-polymerase chain reaction (RT-PCR). Expression levels among the three groups were compared. Logistic regression analysis was conducted to evaluate the relationship between ABCB4 mRNA expression and pregnancy outcomes in women with chronic HBV infection. Results Placental ABCB4 mRNA expression levels decreased in the order of the control group, HBV group, and HBV with ICP group, with statistically significant differences (Z=83.071, P<0.001). In the HBV with ICP group, patients with severe ICP had significantly lower ABCB4 mRNA expression compared to those with mild ICP (Z=3.683, P<0.001). The total incidence of adverse pregnancy outcomes was significantly higher in the HBV with ICP group than in the HBV group (χ²=4.852, P<0.05). Placental ABCB4 mRNA expression was significantly lower in the adverse pregnancy outcome group than in the favorable outcome group (t=8.541, P<0.001). The proportion of patients with ICP and serum total bile acid (TBA), aspartate aminotransferase (AST) and total bilirubin levels were significantly higher in the adverse outcome group (χ²/Z/t value ranging from 4.012 to 19.404, P<0.05). Multivariate logistic regression analysis showed that high expression of ABCB4 mRNA in the placenta was a protective factor against adverse pregnancy outcomes in chronic HBV patients, while the presence of ICP and elevated AST levels were risk factors. The corresponding odds ratios (OR) and 95% confidence intervals (CI) were: 0.463 (0.303-0.706), 3.196 (1.081-9.449), and 1.149 (1.067-1.238), respectively. Conclusion Compared to pregnant women with chronic HBV infection alone, those with concurrent ICP exhibit lower placental ABCB4 mRNA expression and a higher risk of adverse pregnancy outcomes. These findings warrant close clinical attention.

关键词

乙型肝炎病毒感染 / 妊娠期肝内胆汁淤积症 / 胎盘 / 三磷酸腺苷结合盒转运子B亚族成员4 / 妊娠结局

Key words

hepatitis B virus infection / intrahepatic cholestasis of pregnancy / placenta / ATP-binding cassette subfamily B member 4 / pregnancy outcome

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基金资助

金华市科技局重点项目(2021G3G124)