妊娠合并乙肝病毒感染患者血清DNMT1、TIM-3与HBV-DNA病毒载量和妊娠结局的关系分析

摘要 目的：探讨妊娠合并乙肝病毒（HBV）感染患者血清脱氧核糖核酸甲基转移酶1（DNMT1）、T细胞免疫球蛋白粘蛋白-3（TIM-3）与乙型肝炎病毒-脱氧核糖核酸（HBV-DNA）病毒载量和妊娠结局的关系。方法：选取2021年1月～2022年1月南京医科大学第一附属医院收治的186例妊娠合并HBV感染患者为HBV感染组，根据HBV-DNA病毒载量分为阳性组56例和阴性组130例，根据妊娠结局分为结局不良组和结局良好组，另选取同期于南京医科大学第一附属医院进行孕检的150名健康孕妇为对照组。采用酶联免疫吸附法检测血清DNMT1、TIM-3水平。比较HBV感染组与对照组、阳性组与阴性组血清DNMT1、TIM-3水平。采用单因素及多因素Logistic回归分析妊娠合并HBV感染患者妊娠结局不良的影响因素，受试者工作特征（ROC）曲线分析血清DNMT1、TIM-3水平对妊娠合并HBV感染患者妊娠结局不良的预测价值。结果：与对照组比较，HBV感染组血清DNMT1、TIM-3水平升高（P＜0.05）。与阴性组比较，阳性组血清DNMT1、TIM-3水平升高（P＜0.05）。186例妊娠合并HBV感染患者妊娠结局不良发生率为55.38%（103/186）。单因素分析显示，妊娠结局不良与HBV感染孕周、HBV-DNA病毒载量、谷草转氨酶（AST）、谷丙转氨酶（ALT）、DNMT1、TIM-3有关（P＜0.05）。多因素Logistic回归分析显示，HBV-DNA病毒载量阳性和DNMT1＞34.94 ng/mL、TIM-3＞18.96 pg/mL为妊娠合并HBV感染患者妊娠结局不良的独立危险因素（P＜0.05）。ROC曲线分析显示，血清DNMT1、TIM-3水平单独和联合检测预测妊娠合并HBV感染患者妊娠结局不良的曲线下面积分别为0.798、0.791、0.870。结论：妊娠合并HBV感染患者血清DNMT1、TIM-3水平升高与HBV-DNA病毒载量阳性和妊娠结局不良密切相关，血清DNMT1、TIM-3水平联合对妊娠合并HBV感染患者妊娠结局预测价值良好。

Analysis of the Relationship between Serum DNMT1, TIM-3 and HBV-DNA Viral Load and Pregnancy Outcome in Patients with Pregnancy Combined with Hepatitis B Virus Infection

ABSTRACT Objective: To investigate the relationship between serum deoxyribonucleic acid methyltransferase 1(DNMT1),T cell immunoglobulin mucin-3(TIM-3) and hepatitis B virus-deoxyribonucleic acid (HBV-DNA) viral load and pregnancy outcome in patients with pregnancy combined with hepatitis B virus (HBV) infection. Methods: 186 pregnant women with HBV infection who were admitted to The First Affiliated Hospital of Nanjing Medical University from January 2021 to January 2022 were selected as HBV infection group, patients were divided into positive group (56 cases) and negative group (130 cases) according to HBV-DNA viral load, patients were divided into poor outcome group and good outcome group according to the pregnancy outcome, another 150 healthy pregnant women who underwent pregnancy tests at The First Affiliated Hospital of Nanjing Medical University during the same period were selected as control group. Serum DNMT1 and TIM-3 levels were detected by enzyme-linked immunosorbent assay. The levels of serum DNMT1 and TIM-3 were compared between HBV infection group and control group, positive group and negative group. The influencing factors of adverse pregnancy outcomes in pregnant women with HBV infection were analyzed by Univariate and multivariate logistic regression, the predictive value of serum DNMT1 and TIM-3 levels for adverse pregnancy outcomes in pregnant women with HBV infection were analyzed by receiver operating characteristic (ROC) curve. Results: Compared with control group, the levels of serum DNMT1 and TIM-3 in HBV infection group were increased (P<0.05). Compared with negative group, the levels of serum DNMT1 and TIM-3 in positive group were increased (P<0.05). The incidence of adverse pregnancy outcomes in 186 pregnant women with HBV infection was 55.38 % (103/186). Univariate analysis showed that adverse pregnancy outcomes was related to the gestational age of HBV infection, HBV DNA Viral load, aspartate Transaminase (AST), Alanine transaminase (ALT), DNMT1, TIM-3(P<0.05). Multivariate Logistic regression analysis showed that, positive HBV-DNA viral load and DNMT1＞34.94 ng/mL and TIM-3＞18.96 pg/mL were independent risk factors for adverse pregnancy outcomes in pregnant women with HBV infection(P<0.05). ROC curve analysis showed that, the area under the curve of serum DNMT1 and TIM-3 levels alone and in combination to predict adverse pregnancy outcomes in pregnant women with HBV infection by detecting was 0.798, 0.791 and 0.870 respectively. Conclusion: The increase of serum DNMT1 and TIM-3 levels in pregnant women with HBV infection is closely relate to the positive HBV-DNA viral load and adverse pregnancy outcomes, and combination of serum DNMT1 and TIM-3 levels has a good predictive value for pregnancy outcome in pregnant women with HBV infection.