乙型肝炎病毒宫内传播机制研究进展

Research Progress on the Mechanism of Intrauterine Transmission of Hepatitis B Virus

慢性乙型肝炎病毒(hepatitis B virus,HBV)感染者中母婴传播占50%以上,围生期HBV感染者90%以上会发展为慢性携带者,且有较高肝硬化和(或)肝癌的发生风险。宫内感染是乙型肝炎疫苗+乙型肝炎免疫球蛋白联合免疫失败致HBV母婴传播的主要原因。HBV宫内感染途径有生殖细胞感染、经胎盘屏障渗漏、经胎盘细胞感染及外周血单个核细胞(peripheral blood mononuclear cell,PBMC)4种途径。HBV可感染穿越胎盘屏障各细胞层尤其是滋养细胞层,其通过胞内囊泡转运系统穿越滋养细胞,多种细胞因子如白细胞介素等可调节HBV感染滋养细胞,诱导滋养细胞磷脂酰肌醇3激酶/磷酸化蛋白激酶B(phosphatidylinositol 3-kinase/phospho protein kinase B,PI3K/pAKT)和Smad信号通路、表皮生长因子受体(epidermal growth factor receptor,EGFR)/AKT信号通路激活及细胞凋亡减少,从而增加HBV母婴传播风险。对血HBV-DNA>2×10^(5)IU/mL孕妇,妊娠24~28周后可以给予口服替诺福韦抗病毒治疗降低HBV母婴传播风险。

More than 50%of chronic hepatitis B virus(HBV)infections are transmitted from mother to child,and more than 90%of perinatal HBV infections develop into chronic carriers with a higher risk of cirrhosis and/or liver cancer.Intrauterine infection is the main cause of mother-to-child transmission of HBV due to the failure of combined immunization with hepatitis B vaccine and hepatitis B immunoglobulin.HBV intrauterine infection includes four ways:germ cell infection,transplacental barrier leakage,transplacental cell infection and peripheral blood mononuclear cell(PBMC).HBV can infect and cross all cellular layers of the placental barrier,especially the trophoblast layer.HBV traverses trophoblast cells through intracellular vesicle transport system.A variety of cytokines such as interleukin can regulate HBV infection of trophoblast cells.HBV induces the activation of PI3K/pAKT and Smad signaling pathways and EGFR/AKT signaling pathways of trophoblast cells,and then reduces apoptosis,thereby increasing the risk of HBV mother-to-child transmission.Pregnant women with HBV-DNA>2×10^(5) IU/L may take tenofovir orally after 24-28 weeks of pregnancy,so as to reduce the risk of HBV mother-to-child transmission.