合并乙型肝炎病毒感染妊娠期糖尿病孕妇肝功能、免疫功能、细胞因子水平变化及其对不良妊娠结局的影响

Changes and clinical significance of liver function,immune function and cytokine levels in pregnant women with gestational diabetes mellitus complicated with hepatitis B virus infection

目的调查了解合并乙型肝炎病毒(HBV)感染妊娠期糖尿病(GDM)孕妇肝功能、免疫功能及细胞因子水平变化及其对不良妊娠结局的影响。方法选取2017年4月至2020年4月在本院建档并分娩的合并HBV感染GDM孕妇148例(观察组)、单纯GDM孕妇166例(对照组)。检测比较两组肝功能指标(AST、TBA、ALT、TBIL)、免疫功能指标(CD^(3+)、CD^(4+)、CD^(4+)/CD^(8+)、IgM、IgA)、细胞因子指标(TNF-α、IL-4、IFN-γ、IL-10)水平;统计比较两组不良妊娠结局情况,分析孕妇年龄、产次、流产史、体质量指数、HBeAg阳性率及肝功能、免疫功能及细胞因子指标对合并HBV感染GDM孕妇不良妊娠结局的影响。结果观察组AST、ALT、TBA、TBIL、IgM、IgA、TNF-α、IL-4、IL-10水平均高于对照组,CD^(3+)、CD^(4+)、CD^(4+)/CD^(8+)、IFN-γ水平均低于对照组,差异有统计学意义(P<0.05)。观察组早产、胎儿宫内窘迫、产后出血、低出生体重儿等不良妊娠结局发生率为39.86%(59/148),高于对照组的12.65%(21/166),差异有统计学意义(χ2=33.736,P<0.05)。单因素分析显示:妊娠结局不良组孕妇年龄、流产史、HBeAg阳性率及AST、ALT、TBA、TBIL、IgM、TNF-α、IL-4、IL-10水平均高于妊娠结局良好组,CD^(3+)、CD^(4+)、IFN-γ水平均低于妊娠结局良好组,差异有统计学意义(P<0.05)。Logistic回归分析显示:年龄(OR=1.559,95% CI=1.020~2.384)、AST(OR=1.099,95% CI=1.003~1.204)、ALT(OR=1.150,95% CI=1.016~1.302)、TBIL(OR=1.341,95% CI=1.052~1.710)、IL-10(OR=1.918,95% CI=1.065~3.453)、HBeAg阳性率(OR=16.677,95% CI=1.142~243.451)均是合并HBV感染GDM孕妇发生不良妊娠结局的危险因素(P<0.05),而CD^(3+)(OR=0.669,95% CI=0.483~0.928)、CD^(4+)(OR=0.717,95% CI=0.554~0.929)、IFN-γ(OR=0.866,95% CI=0.757~0.991)则是保护性因素(P<0.05)。结论 HBV感染可能加重GDM孕妇肝功能损伤、免疫功能紊乱、细胞因子分泌失衡,且与不良妊娠结局密切相关,年龄、AST、ALT、TBIL、IL-10、HBeAg阳性率是合并HBV感染GDM孕妇发生不良妊娠结局的危险因素,而CD^(3+)、CD^(4+)、IFN-γ则是保护性因素。

Objective:To investigate the changes of liver function,immune function and cytokine levels in pregnant women with gestational diabetes mellitus(GDM)complicated with hepatitis B virus(HBV)infection and the risk factors of adverse pregnancy outcomes.Methods:148 GDM pregnant women with HBV infection(observation group)and 166 pregnant women with simple GDM(control group)were selected from April 2017 to April 2020 in our hospital.Liver function indexes(AST,TBA,ALT,TBIL),immune function indexes(CD^(3+)、CD^(4+)、CD^(4+)/CD^(8+)、IgM、IgA),cytokines(TNF-α、IL-4、IFN-γ、IL-10)were detected and compared between the two groups.The adverse pregnancy outcomes of the two groups were compared statistically.To analyze the influence of maternal age,parity,abortion history,body mass index,HBeAg positive rate,liver function,immune function and cytokines on adverse pregnancy outcome of GDM pregnant women with HBV infection.Results:The levels of AST,ALT,TBA,TBIL,IgM,IgA,TNF-α,IL-4 and IL-10 in the observation group were higher than those in the control group,and the levels of CD^(3+),CD^(4+),CD^(4+)/CD^(8+),IFN-γ in the observation group were lower than those in the control group(P<0.05).The incidence of premature delivery,fetal distress,postpartum hemorrhage,low birth weight infants and other adverse pregnancy outcomes in the observation group was 39.86%(59/148),which was higher than 12.65%(21/166)of the control group,and the difference was statistically significant(χ2=33.736,P<0.05).Univariate analysis showed that:the age,abortion history,HBeAg positive rate,AST,ALT,TBA,TBIL,IgM,TNF-α,IL-4,IL-10 levels in the poor pregnancy outcome group were higher than those in the good pregnancy outcome group,and the levels of CD^(3+),CD^(4+),IFN-γ in the poor pregnancy outcome group were lower than those in the good pregnancy outcome group(P<0.05).Logistic regression analysis showed that:the age(or=1.559,95% CI=1.020~2.384),AST(or=1.099,95% CI=1.003~1.204),ALT(or=1.150,95% CI=1.016~1.302),TBIL(or=1.341,95% CI=1.052~1.710),IL-10(or=1.918,95% CI=1.065~3.453),HBeAg positive rate(or=16.677,95% CI=1.065~3.453)However,CD^(3+)(or=0.669,95% CI=0.483~0.928),CD^(4+)(or=0.717,95% CI=0.554~0.929),IFN-γ(or=0.866,95% CI=0.757~0.991)were protective factors(P<0.05).Conclusion:HBV infection may aggravate the liver function damage,immune function disorder and cytokine secretion imbalance of GDM pregnant women,and it is closely related to the adverse pregnancy outcome.Age,AST,ALT,TBIL,IL-10,HBeAg positive rate are the risk factors of adverse pregnancy outcomes in GDM pregnant women with HBV infection,while CD^(3+),CD^(4+),IFN-γ are protective factors.