HBeAg阳性妊娠慢性HBV携带者母婴阻断停药后肝炎活动的危险因素研究

Research on risk factors for hepatitis B virus(HBV)reactivation in HBeAg-positive pregnant chronic hepatitis B carriers after treatment cessation

目的观察HBeAg阳性妊娠慢性HBV携带者启动以母婴阻断为目的的抗病毒治疗基线至产后96周内HBV RNA、HBV DNA、qHBsAg、qHBeAg、ALT等指标的动态变化,分析产后96周内肝炎活动的危险因素。方法回顾性纳入接受预防性抗病毒治疗并于产后12周内停药、且完成产后96周随访的妊娠HBeAg阳性患者,观察抗病毒治疗基线、妊娠36周、产后停药时和/或产后24周、产后96周HBV RNA、HBV DNA、qHBsAg、qHBeAg以及生化学指标的动态变化。结果共纳入146例中位治疗时间为16.4周的HBeAg阳性妊娠慢性HBV携带者。抗病毒治疗期间HBV DNA水平及qHBeAg逐渐下降,HBV RNA逐渐增高,qHBsAg水平在孕36周时较基线降低,停药时升高超过基线水平。产后24周上述指标均反弹接近或超过基线水平。产后96周随访,共5例患者发生HBeAg血清学转换,无一例发生HBsAg清除。产后停药时与产后24周肝炎活动比例最高(30.1%vs.30.8%),但随访至产后96周,仅14例(9.59%)患者因肝炎活动需抗病毒干预。根据是否再次启动抗病毒治疗将患者分为复发组(n=14)与未复发组(n=132)。10例患者在停药6个月以后复发,中位复发时间13.5月。两组间抗病毒治疗药物类型、基线至孕36周HBeAg降幅的差异具有统计学意义。结论HBeAg阳性妊娠慢性HBV携带者预防性抗病毒治疗期间及停药后均有不同比例肝炎活动,停药时、产后24周达高峰,但仅少数患者需再次抗病毒干预,且与HBV活动相关的肝炎发作多发生在停药6个月以后,应加强停药后的长期规律随访。抗病毒基线至孕36周HBeAg降幅是预测产后停药肝炎活动的独立危险因素。

Objective To observe the dynamic changes of HBV RNA,HBV DNA,qHBsAg,qHBeAg and biochemical parameters from initiated antiviral therapy to 96 weeks postpartum in HBeAg-positive pregnant chronic hepatitis B carriers,and to analyze the risk factors for hepatitis flares within 96 weeks after treatment cessation.Methods Pregnant HBeAg-positive patients receiving antiviral prophylaxis and ceasing treatment postpartum were included.HBV RNA,HBV DNA,qHBsAg,qHBeAg,and biochemical parameters were measured at antiviral therapy baseline,at 36 weeks of gestation,at treatment withdrawal postpartum,and/or at 24 weeks postpartum.Virological and biochemical parameters were regularly examined until 96 weeks postpartum.Results 146 patients with a median treatment duration of 16.4 weeks were enrolled.HBV DNA levels and qHBeAg gradually decreased during antiviral therapy,while HBV RNA gradually increased.qHBsAg levels decreased at 36 weeks of gestation compared to baseline,but increased at treatment withdrawal postpartum.All these indicators rebounded and approached or exceeded baseline levels at 24 weeks postpartum.HBeAg seroconversion at 96 weeks postpartum occurred in 5 patients while none experienced HBsAg clearance.The proportion of hepatitis flares was highest at treatment withdrawal postpartum and 24 weeks postpartum(30.1%vs.30.8%)but only 14 patients(9.59%)required antiviral intervention due to hepatitis flares.According to whether antiviral treatment was restarted,patients were divided into recurrence group(n=14)and non-recurrence group(n=132).Ten patients in the relapse group experienced hepatitis flares after 6 months of treatment cessation,with a median relapse time of 13.5 months.The difference in the type of antiviral therapy drugs and the magnitude of HBeAg decline from baseline to 36 weeks of gestation between the two groups is statistically significant.Conclusion HBeAg-positive pregnant chronic hepatitis B carriers have a certain proportion of hepatitis flares during receiving antiviral prophylaxis and ceasing treatment.The peak occurs at treatment withdrawal postpartum and at 24 weeks postpartum.However,only a small number of patients require further antiviral intervention.The vast majority(71.4%)of postpartum hepatitis flares occured more than 6 months,so it is recommended to be strengthened long-term regular follow-up after treatment discontinuation.The decline levels of HBeAg from the antiviral baseline to the 36 weeks of gestation are independent risk factors for predicting hepatitis flares after treatment cessation.