目的探讨乙型肝炎患者妊娠期耐药的原因及管理策略。方法收集2007年1月1日至2012年12月31日在北京地坛医院足月分娩、妊娠期服用拉米夫定或替比夫定出现耐药的20例乙型肝炎患者的病历资料进行回顾性分析,主要分析指标为妊娠前后抗病毒药物应用情况、妊娠期出现耐药的时间及应对措施、HBV DNA载量、肝功能以及母婴结局等。结果拉米夫定组患者12例,年龄26~38岁,平均(31±3)岁,妊娠前应用拉米夫定100 mg/d,治疗时间1.5~8.0年;其中3例在应用恩替卡韦2年后改用拉米夫定。替比夫定组患者8例,年龄27~34岁,平均(31±2)岁,妊娠前应用替比夫定600 mg/d,治疗时间2.0~4.5年;其中1例在应用恩替卡韦2年后改用替比夫定。耐药发生在妊娠0~12、13~27、28~40周者拉米夫定组分别为1、2、9例,替比夫定组分别为1、1、6例,发生在妊娠28~40周者共15例(75%)。拉米夫定组12例中4例改用替诺福韦300 mg/d单药治疗,3例在妊娠28周后加用阿德福韦酯10 mg/d联合治疗;4例继续用拉米夫定,产后加用阿德福韦酸治疗;1例改用替比夫定无效,产后加用阿德福韦酯治疗。替比夫定组8例中2例改用替诺福韦300 mg/d单药治疗,其余6例继续服用替比夫定,产后加用阿德福韦酯10 mg/d联合治疗。20例孕妇均单胎足月顺产。拉米夫定组1例新生儿出生时静脉血HBV DNA为1.56×10~6拷贝/ml,诊断为宫内感染,考虑与母亲耐药有关。替比夫定组2例新生儿中1例出生时右耳附耳,另1例出现颅内出血及贫血,均与药物及耐药无关。对20名新生儿随访2~57个月,均生长发育正常。结论接受抗病毒治疗的乙型肝炎孕妇,尤其是妊娠前抗病毒治疗时间较长者,在妊娠期应加强病毒耐药监测。耐药可能导致孕妇肝病加重,并增加乙型肝炎病毒母婴传播的风险。出现耐药后应密切监测患者肝功能,且在充分告知风险、权衡利弊、患者知情同意的情况下改变治疗方案。替诺福韦是妊娠期拉米夫定或替比夫定耐药患者的最佳选择。 Objective To investigate the causes and management strategies of drug resistance in hepatitis B patients during pregnancy. Methods A retrospective review was made on the medical records of 20 hepatitis B patients who had full-term childbirth and were taking lamivudine or telbivudine during pregnancy in Beijing Ditan Hospital from January 1, 2007 to December 31, 2012. Sex analysis, the main analysis indicators for the application of antiviral drugs before and after pregnancy, pregnancy resistance time and response measures, HBV DNA load, liver function and maternal and infant outcomes. Results In the lamivudine group, 12 patients (aged 26-38 years, mean, 31 ± 3 years) were treated with lamivudine 100 mg / d before treatment and the treatment time was 1.5-8.0 years. Three of them were treated with entecavir 2 After switching to lamivudine. Telbivudine group of 8 patients, aged 27 to 34 years, mean (31 ± 2) years of age, before the application of telbivudine 600 mg / d, the treatment time 2.0-4.5 years; 1 case of entecavir 2 years After switching to telbivudine. Resistance occurred in 0-12, 13-27, 28-40 weeks of pregnancy in patients with lamivudine were 1,2,9 cases, telbivudine group were 1,1,6 cases, occurred in pregnancy 28 A total of 15 patients (~ 75%) ~ 40 weeks. Four of the 12 patients in the lamivuvidine group were treated with tenofovir 300 mg / d monotherapy, and three were given adefovir dipivoxil 10 mg / d after 28 weeks of gestation. Four patients Mifudin, postpartum plus adefovir acid treatment; 1 case of switch to telbivudine ineffective, postpartum plus adefovir dipivoxil treatment. Two of the eight patients in the telbivudine group were treated with tenofovir 300 mg / d monotherapy, and the remaining six patients were treated with telbivudine plus adefovir dipivoxil 10 mg / d postpartum. Twenty pregnant women were born with full term asystole. One patient with lamivudine group had HBV DNA of 1.56 × 10 ~ 6 copies / ml at birth, which was diagnosed as intrauterine infection, which was considered to be related to maternal drug resistance. One of the two newborn infants in telbivudine group had right ear appendages at birth and the other one had intracranial hemorrhage and anemia, which were unrelated to drug and drug resistance. Twenty newborns were followed up for 2 to 57 months and both grew normally. Conclusions Hepatitis B pregnant women receiving antiviral therapy, especially pre-pregnancy antiviral therapy, should be monitored during pregnancy. Resistance may result in increased liver disease in pregnant women and increase the risk of mother-to-child transmission of hepatitis B virus. Drug resistance should be closely monitored after the patient’s liver function, and the full informed of the risks, weigh the pros and cons, patients with informed consent to change the treatment plan. Tenofovir is the best choice for lamivudine or telbivudine-resistant patients during pregnancy.