药物不良反应杂志
藥物不良反應雜誌
약물불량반응잡지
ADVERSE DRUG REACTIONS JOURNAL
2013年
2期
69-72
,共4页
曹彦君%方芳%刘敏%蔡晧东
曹彥君%方芳%劉敏%蔡晧東
조언군%방방%류민%채호동
慢性乙型肝炎%妊娠%抗病毒治疗%耐药
慢性乙型肝炎%妊娠%抗病毒治療%耐藥
만성을형간염%임신%항병독치료%내약
Hepatitis B,chronic%Pregnancy%Antiviral therapy%Drug resistance
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,替比夫定组分另为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,产后加用阿德福韦酯治疗；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1.56×106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.
目的 探討乙型肝炎患者妊娠期耐藥的原因及管理策略. 方法 收集2007年1月1日至2012年12月31日在北京地罈醫院足月分娩、妊娠期服用拉米伕定或替比伕定齣現耐藥的20例乙型肝炎患者的病歷資料進行迴顧性分析,主要分析指標為妊娠前後抗病毒藥物應用情況、妊娠期齣現耐藥的時間及應對措施、HBV DNA載量、肝功能以及母嬰結跼等. 結果 拉米伕定組患者12例,年齡26～38歲,平均(31±3)歲,妊娠前應用拉米伕定100 mg/d,治療時間1.5 ～8.0年；其中3例在應用恩替卡韋2年後改用拉米伕定.替比伕定組患者8例,年齡27～34歲,平均(31±2)歲,妊娠前應用替比伕定600 mg/d,治療時間2.0 ～4.5年；其中1例在應用恩替卡韋2年後改用替比伕定.耐藥髮生在妊娠0 ～12、13～27、28 ～ 40週者拉米伕定組分彆為1、2、9例,替比伕定組分另為1、1、6例,髮生在妊娠28 ～ 40週者共15例(75％).拉米伕定組12例中4例改用替諾福韋300 mg/d單藥治療,3例在妊娠28週後加用阿德福韋酯10 mg/d聯閤治療；4例繼續用拉米伕定,產後加用阿德福韋酯治療；1例改用替比伕定無效,產後加用阿德福韋酯治療.替比伕定組8例中2例改用替諾福韋300 mg/d單藥治療,其餘6例繼續服用替比伕定,產後加用阿德福韋酯10 mg/d聯閤治療.20例孕婦均單胎足月順產.拉米伕定組1例新生兒齣生時靜脈血HBV DNA為1.56×106拷貝/ml,診斷為宮內感染,攷慮與母親耐藥有關.替比伕定組2例新生兒中1例齣生時右耳附耳,另1例齣現顱內齣血及貧血,均與藥物及耐藥無關.對20名新生兒隨訪2 ～ 57箇月,均生長髮育正常. 結論 接受抗病毒治療的乙型肝炎孕婦,尤其是妊娠前抗病毒治療時間較長者,在妊娠期應加彊病毒耐藥鑑測.耐藥可能導緻孕婦肝病加重,併增加乙型肝炎病毒母嬰傳播的風險.齣現耐藥後應密切鑑測患者肝功能,且在充分告知風險、權衡利弊、患者知情同意的情況下改變治療方案.替諾福韋是妊娠期拉米伕定或替比伕定耐藥患者的最佳選擇.
목적 탐토을형간염환자임신기내약적원인급관리책략. 방법 수집2007년1월1일지2012년12월31일재북경지단의원족월분면、임신기복용랍미부정혹체비부정출현내약적20례을형간염환자적병력자료진행회고성분석,주요분석지표위임신전후항병독약물응용정황、임신기출현내약적시간급응대조시、HBV DNA재량、간공능이급모영결국등. 결과 랍미부정조환자12례,년령26～38세,평균(31±3)세,임신전응용랍미부정100 mg/d,치료시간1.5 ～8.0년；기중3례재응용은체잡위2년후개용랍미부정.체비부정조환자8례,년령27～34세,평균(31±2)세,임신전응용체비부정600 mg/d,치료시간2.0 ～4.5년；기중1례재응용은체잡위2년후개용체비부정.내약발생재임신0 ～12、13～27、28 ～ 40주자랍미부정조분별위1、2、9례,체비부정조분령위1、1、6례,발생재임신28 ～ 40주자공15례(75％).랍미부정조12례중4례개용체낙복위300 mg/d단약치료,3례재임신28주후가용아덕복위지10 mg/d연합치료；4례계속용랍미부정,산후가용아덕복위지치료；1례개용체비부정무효,산후가용아덕복위지치료.체비부정조8례중2례개용체낙복위300 mg/d단약치료,기여6례계속복용체비부정,산후가용아덕복위지10 mg/d연합치료.20례잉부균단태족월순산.랍미부정조1례신생인출생시정맥혈HBV DNA위1.56×106고패/ml,진단위궁내감염,고필여모친내약유관.체비부정조2례신생인중1례출생시우이부이,령1례출현로내출혈급빈혈,균여약물급내약무관.대20명신생인수방2 ～ 57개월,균생장발육정상. 결론 접수항병독치료적을형간염잉부,우기시임신전항병독치료시간교장자,재임신기응가강병독내약감측.내약가능도치잉부간병가중,병증가을형간염병독모영전파적풍험.출현내약후응밀절감측환자간공능,차재충분고지풍험、권형리폐、환자지정동의적정황하개변치료방안.체낙복위시임신기랍미부정혹체비부정내약환자적최가선택.
Objective To explore the cause of drug resistance in patients with chronic hepatitis B during pregnancy and the management policy.Methods The clinical data of 20 pregnant women with chronic hepatitis B received lamivudine (LAM) or telbivudine (LdT),developed drug resistance during pregnancy,and delivered full-term newborns from January 1,2007 to December 31,2012 in Beijing Ditan Hospital were collected and analyzed retrospectively.The main indicators of analysis included the situation of antiviral drug use before and after pregnancy,the occurrence time of drug resistance and the restriction measures during pregnancy,HBV-DNA load,liver function,maternal and neonatal outcomes.Results LAM group comprised 12 patients with age of 26 to 38 (31 ±3) years,received LAM 100 mg/d for 1.5 to 8 years before pregnancy.Of them,3 patients had received entecavir for 2 years and then changed to LAM.LdT group comprised 8 patients with age of 27 to 34 (31 ± 2) years,received LdT 600 rng/d for 2.0 to 4.5 years.Of them,a patient had received entecavir for 2 years and then changed to LdT.The drug resistance occurred during 0-12,13-27,and 28-40 weeks of pregnancy in LAM group in 1,2,and 9 cases,in LdT group in 1,1,and 6 cases,respectively.A total of 15 (75％) patients developed drug resistance during 28-40 weeks of pregnancy.Of 12 patients in LAM group,4 substituted tenofovir (TDF) 300 mg/d for LAM,3 received LAM and added adefovir dipivoxil after 28 weeks of pregnancy,4 received LAM continually and added adefovir dipivoxil after childbirth,another one substituted telbivudine for LAM but was not effective and added adefovir dipivoxil after childbirth.Of 8 patients in LdT group,2 substituted TDF 300 mg/d for LdT,6 received LdT continually and combined with adefovir dipivoxil 10 mg/d after childbirth.Twenty pregnant women were all singleton and had full-term natural labor.In LAM group,a newbom's venous HBV DNA load was 1.56 × 106 copies/ml and diagnosed as intrauterine infection associated with mother's drug resistance.In LdT group,a newborn developed annexal ear on the right side,another newborn had intracranial bleeding and anemia,both were not correlated with drug and mothers'drug resistance.Twenty newborns were followed-up for 2 to 57 months,all had normal growth and development.Conclusions Drug resistance monitoring during pregnancy should be applied for chronic hepatitis B women receiving antiviral therapy,especially for the patients receiving antiviral therapy for a long time before pregnancy.The drug resistance may lead to liver disease aggravation and increase the risk degree of hepatitis B virus motherto-infant transmission.When drug resistance occurred,the liver funcion should be monitored regularly and the therapy should be changed in the following circumstances:fully informed the risk,weighed the advantage and disadvantage,and signed informed consent.TDF is the best choice for LAM or LdT-resistant patients during pregnancy.
