早中孕期低病毒载量乙肝感染孕妇晚孕期病毒复制升高危险因素分析

Analysis of risk factors for elevated viral replication in pregnant women with low viral load in the first and second trimesters of hepatitis B infection in late pregnancy

目的:分析孕早中期低载量HBV DNA孕妇妊娠期病毒载量升高及出现高病毒血症的临床特征,为临床早期识别该人群提供依据。方法:采用回顾性巢式病例对照研究,纳入2020年1月至2022年9月就诊于广州医科大学附属第五医院的HBV感染孕妇,收集患者孕12~24周、孕32周~分娩两个时间段的临床特征、血清病毒学、肝功能等生化指标。依据孕后期HBV DNA变化情况,分为HBV DNA升高组和HBV DNA非升高组,观察妊娠期病毒载量升高的发生率,分析两组患者的基本特征、基线病毒学及肝功能等情况,探索病毒载量升高的危险因素。亚组分析HBV DNA升高组孕妇出现高病毒血症的危险因素并回访其婴儿HBV感染情况。结果:共纳入251例HBV感染孕妇,HBV DNA升高组39例(15.54%),HBV DNA非升高组212例(84.46%)。HBV DNA升高组孕妇基线ALT≥19U/L及HBeAg阳性占比均高于非升高组(P<0.05);两组患者的年龄、胎次、孕前BMI、基线病毒载量比较,差异均无统计学意义(P>0.05)。多因素logistic回归分析显示,HBeAg阳性(OR=6.31,95%CI为1.44~27.63,P<0.05)和基线ALT≥19U/L(OR=2.79,95%CI为1.12~6.95,P<0.05)是妊娠期HBV DNA升高的独立危险因素。病毒载量升高亚组分析中,出现高病毒血症孕妇共8例(3.19%),与未出现高病毒血症孕妇(31例)相比,年龄小[(28.0±3.21)岁vs(32.45±4.50)岁,P<0.05]、头胎比例高(75%vs 29%,P<0.05)、HBeAg阳性占比大(12.8%vs 3.3%,P<0.05)及基线HBV DNA均≥100IU/mL(100%vs 19.4%,P<0.05)。结论:孕早中期低载量HBV DNA孕妇妊娠期病毒载量升高的发生率为15.54%,其中3.19%于孕晚期出现高病毒血症。依据指南在孕12~24周HBV病毒学监测后,需间隔4~6周且不晚于孕32周进行HBV DNA复测,尤其应关注年龄<30岁、孕12~24周ALT≥19U/L、头胎、基线HBV DNA≥100IU/mL或HBeAg阳性的孕妇。

Objective:To analyze the clinical characteristics of pregnant women with low HBV DNA load in the first and middle trimesters of pregnancy,whose viral load was rising and the occurrence of high viremia,so as to provide a basis for early clinical identification of this population.Methods:A retrospective nested case-control study was conducted to collect the clinical characteristics,serum virology,liver function and other biochemical parameters of pregnant women with HBV infection attending the Fifth Hospital of Guangzhou Medical University from January 2020 to September 2022,at two time periods:12~24 weeks of gestation and 32 weeks of gestation to delivery.Based on the changes in HBV DNA during the third trimester,patients were divided into HBV DNA elevation group and HBV DNA non-elevation group to observe the incidence of viral load elevation during pregnancy.The basic characteristics,baseline virology and liver function of the two groups were also analysed to explore the risk factors for elevated viral load.Subgroup analysis of risk factors for high levels of viremia in pregnant women in the HBV DNA elevation group and follow-up of HBV infection in their infants.Result:A total of 251 pregnant women with HBV infection were included,39(15.54%)in the HBV DNA elevation group and 212(84.46%)in the HBV DNA non-elevation group.The proportion of pregnant women with baseline ALT≥19U/L and HBeAg positivity were higher in the HBV DNA elevated group than those in the non-elevated group(P<0.05).There were no significant differences in age,gestational age,pre-pregnancy BMI,or baseline viral load between the two groups(P>0.05).Multi-factorial logistic regression analysis showed that HBeAg positivity(OR 6.31,95%CI 1.44~27.63,P<0.05)and baseline ALT≥19U/L(OR 2.79,95%CI 1.12~6.95,P<0.05)were independent risk factors for HBV DNA drift during pregnancy.In the subgroup analysis of rising viral load,8 cases(3.19%)of pregnant women with high levels of viremia were younger than those without high levels of viremia(n=31)(28.0±3.21 vs 32.45±4.50,P<0.05),more first-borns(75%vs 29%,P<0.05),more HBeAg-positive(12.8%vs 3.3%,P<0.05)and baseline HBV DNA≥100IU/mL(100%vs 19.4%,P<0.05).Conclusions:15.54%of pregnant women with low viral load in the first and second trimesters had elevated viral loads during pregnancy,and 3.19%had high virulence in the third trimester.After HBV virological monitoring at 12~24 weeks of gestation,HBV DNA re-examination should be performed every 4~6 weeks,and no later than 32 weeks of gestation.Pay particular attention to age<30 years,ALT≥19U/L,first-born,HBeAg-positive status or HBV DNA≥100IU/mL at baseline.