乙型肝炎免疫球蛋白阻断乙肝病毒母婴传播过程中病毒S区基因变异的研究

Study on the S region gene mutation of hepatitis B virus during prevention of HBV transmission in uterus with hepatitis B immunoglobulin

目的了解乙型肝炎免疫球蛋白(HBIG)在阻断母婴传播过程中S基因变异的特点,比较与未予阻断者的差异,探讨基因变异与宫内传播的关系,协助评价HBIG的治疗安全性。方法将18对乙型肝炎病毒(HBV)携带母亲及其宫内感染新生儿按母亲产前处理分为HBIG组8对,母亲于产前3月起肌肉注射HBIG 200-400 IU至分娩前;对照组10对,母亲产前不接受HBIG者。巢式PCR扩增HBV S基因片段并直接测序。以每对病例第一份(母亲孕中期)血清HBV株S基因区氨基酸(或核苷酸)作为标准,对每对病例第二份血清(母亲分娩前)和第三份血清(新生儿)HBV株进行分析。结果HBV S区碱基替代突变率和氨基酸变异数在HBIG组和对照组之间的差异均无统计学意义;18例宫内感染儿17例其病毒株与母亲分娩前的优势株一致,其中4例为S区变异株;18例宫内感染儿病毒株分型B型adw2 12例,C型adrq+6例。结论无症状携带HBV孕妇产前使用现有剂量HBIG至临产并未增加HBV S区的变异。HBV S区变异株和未变异株均可经宫内传播,宫内感染发生于孕后期;HBV S区变异并非发生宫内感染的主要原因。

Objective To study the relationship between hepatitis B immunoglobulin （HBIG） injection before delivery and hepatitis B virus （HBV） S gene mutation. Methods 18 neonates infected with HBV in uterus and their mothers were divided to a） HBIG group （8） in which their mothers received HBIG injection before delivery and b） control group （10） in which their mothers never received any treatment. HBV DNA fragments were amplified by nest-PCR from sera of these neonates and their mothers. S gene region of these HBV DNA fragments were directly sequenced and data on mutations was analyzed. Results There was no significant difference on nueleotide and amino acid changes in the S gene between the HBIG group and the control group. The majority HBV strains of newborn （17/18） were identical to their mother＇s dominant strains before delivery, including four mutation HBV strains. Among 18 newborns with HBV intrauterine infection, 12 were infected by B type （adw2）, and 6 by C type （adrq^＋ ）. Conclusion Mothers who were asymptomatie HBsAg carrier and received injections of HBIG before delivery would not be influenced by HBV S gene mutation. HBV intrauterine transmission with or without gene mutation might occur in the third-trimester of pregnancy. Gene mutation of HBV was not the main factor in intrauterine transmission of HBV.