HBV感染的E抗原阳性的免疫耐受期患者产后母乳喂养的安全性研究

Safety study on postpartum breastfeeding for HBV infected patients with E antigen positive and in immune tolerant phase

目的乙肝病毒感染的母亲中，很多医生和患者对于母乳喂养仍有疑虑，评价孕期采用核苷类似物进行母婴阻断的HBeAg阳性的免疫耐受期患者，产后停药母乳喂养的安全性。方法2015年12月1日至2017年5月1日，共纳入患者415例，母乳喂养组220例，人工喂养组195例。本研究为前瞻性观察研究，对于HBeAg阳性，HBV-DNA〉2＊10E＋5 IU/ml的患者，孕24～28周开始替比夫定或替诺福韦抗病毒治疗。产后常规进行乙肝疫苗和乙肝免疫球蛋白主被动联合免疫。孕期无肝功能异常者，停药产后自愿母乳喂养，对照组为人工喂养组，随访至7月龄。主要观察指标为：产妇肝功能异常的比率、和抗-HBs的滴度；次要观察指标为：母亲产后6周的HBV-DNA载量和新生儿HBsAg的阳性率。结果产后停药后6个月内，两组患者肝功能异常比例分别为：母乳喂养组29 /220，人工喂养组30/195，差异无统计学意义（P＝0.521），两组患者产后继续抗病毒的比例母乳喂养20 /200，人工喂养组25/195，差异无统计学意义（P＝0.223）。两组患者7月龄婴儿时抗-HBs滴度分别为747.62±374.08 mlU/ml和709.76±374.32 mlU/ml，P〉0.05，差异无统计学意义。两组患者1月龄和7月龄新生儿HBsAg阳性率无明显差异。母乳喂养组患者HBV-DNA平均值为（1.17±1.82）E＋8IU/ml，高于人工喂养组患者的HBV-DNA平均值：（1.12±0.39）E＋8IU/ml。结论HBeAg阳性的HBV感染的免疫耐受期患者，产后停药进行母乳喂养，母亲肝功能异常比例和7月龄婴儿抗-HBs抗体滴度无明显差异。

ObjectiveMany physicians and patients still have concerns about the safety of breastfeeding in mothers infected with hepatitis B virus; we evaluate the safety of the newborn and the women with HBeAg positive and high viral load, who received nucleoside analogues to block maternal to child transmisssion and selected postpartum breastfeeding after drug discontinuance.MethodsThis prospective, observational study enrolled 60 HBeAg positive patients and HBV-DNA 〉2＊10E＋ 5 IU/ml, all patients started antiviral treatment for blocking maternal to child transmission at 24-28 weeks of pregnancy. All the newborns received the active-passive immunization therapy with hepatitis B immunoglobulin （HBIG） and HBVac. After the delivery, patients with normal liver function discontinued the antiviral drug and selected breastfeeding voluntarily. The safety of breastfeeding were compared with patients selected artificial feedings, they were followed up for 7 months. Primary measurements were the proportion of mothers with abormal liver function after stopping the drug and the level of newborn’s anti-HBs at 6 months of age; secondary measurements were the positive rate of neonatal HBsAg and the HBV-DNA value of the patients at 6 weeks postpartum.ResultsFrom December 1, 2015 to May 1, 2017, 415 patients were enrolled in Beijing You’an Hospital Affiliated to the Capital Medical University and all these patients were born following full-term single-child pregnancy. After the delivery and drug withdrawal, there was no significant difference in the incidence of ALT elevation between the breast fed group and the artificially fed group： 29 /220 versus 30/195, （χ2=0.411, P=0.521）. Patients continued to take the antiviral medicines between the breast feeding group and the artificial feeding group： 15 /220 versus 20/195, （χ2=1.487, P=0.223）, there were no significant differences between them （P〉 0.05）. At the month 7, there were no significant difference between the breast fed group and the artificially fed group （747.62±374.08 mlU/ml versus 709.76±374.32 mlU/ml, t-value： 0.309, P-value〉0.05）. At birth, hepatitis B surface antigen （HBsAg） was detected in 15/220 and 20/195 of newborns in the breast feeding and artificially fed groups, respectively. At month 7, an intention-to-treat analysis indicated 0/220 of HBsAg infants from the breast fed versus 0/195 in the artificially fed group （P〉0.05） and no significant difference was found in the rate of positive HBsAg between the two groups. In the breast fed group, the mean HBV DNA at baseline was significantly higher than that of the artificially fed group： （1.17±1.82） E＋ 8 IU/ml versus （1.12±0.39）E＋ 8 IU/ml, and the difference was statistically significant.ConclusionsWe have not found the relationship between the rate of neonatal infection and the increase of maternal abnormal liver function in HBeAg positive and high viral load patients, who chose breastfeeding after drug discontinuance.