替诺福韦酯治疗妊娠早期慢性乙型肝炎的效果及对母婴阻断的有效性
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摘要
目的探讨慢性乙型肝炎(CHB)妇女妊娠早期使用替诺福韦酯(TDF)抗病毒的疗效及母婴阻断有效性。方法选择2014年7月-2016年12月在南昌第九医院门诊及住院的CHB孕妇164例及其分娩的新生儿为观察对象,按患者意愿分为治疗组(n=80,孕妇在妊娠早期予以TDF 300 mg/d,并在妊娠结束后按照CHB的抗病毒处理原则进行治疗)和对照组(n=84,不接受抗病毒治疗)。2组婴儿出生后均接受乙型肝炎免疫球蛋白和乙型肝炎疫苗。观察孕期肝、肾功能,电解质、心肌酶谱,血、尿常规,HBV血清标志物、HBV DNA的变化及不良反应。检测婴儿出生时、6个月及12个月时HBs Ag、HBV DNA,评价新生儿HBV感染情况、生长发育情况及并发症,并进行Apgar评分。计量资料2组间比较采用t检验;计数资料2组间比较采用χ~2检验。结果治疗组与对照组ALT复常率、HBV DNA阴转率在妊娠18、24和36周的比较差异均有统计学意义(ALT复常率:χ~2值分别为19. 145、24. 990、36. 414,P值均<0. 001; HBV DNA阴转率:χ~2值分别为75. 526、107. 412、38. 138,P值均<0. 001)。在婴儿出生时、出生后6个月及12个月时检查,治疗组与对照组婴儿HBsAg阳性率、HBV DNA阳性率比较差异均有统计学意义(HBsAg阳性率:χ~2值分别为6. 089、5. 074、5. 074,P值均<0. 05; HBV DNA阳性率:χ~2值均为5. 074,P值均<0. 05)。2组新生儿Apgar评分差异无统计学意义(P> 0. 05),生长发育指标均在正常婴儿范围内。结论妊娠早期开始使用替诺福韦酯能恢复肝功能,并可安全有效的阻断HBV垂直传播。
Objective To investigate the antiviral effect of tenofovir disoproxil( TDF) in women with chronic hepatitis B( CHB) and its effect in blocking mother-to-child transmission of CHB during early pregnancy. Methods A total of 164 pregnant women who were diagnosed with CHB in Nanchang Ninth Hospital from July 2014 to December 2016 were enrolled,and their neonates were also enrolled as subjects. According to their will,the patients were divided into treatment group with 80 patients and control group with 84 patients. The patients in the treatment group were given TDF 300 mg/d during early pregnancy,followed by antiviral therapy for CHB after delivery,and those in the control group did not receive antiviral therapy. All neonates were given hepatitis B immunoglobulin and hepatitis B vaccine after birth.The changes in liver and renal function,electrolytes,myocardial zymogram,routine blood and urine test results,HBV serum markers,and HBV DNA were observed,and adverse reactions were recorded. HBsAg and HBV DNA were measured for infants at birth and at 6 and 12 months after birth; HBV infection,growth and development,and complications were evaluated,and Apgar score was determined. The t-test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between groups. Results There were significant differences between the treatment group and the control group in alanine aminotransferase( ALT) normalization rate,and HBV DNA clearance rate at 18,24,and 36 weeks of pregnancy( ALT normalization rate: χ~2= 19. 145,24. 990,and 36. 414,all P < 0. 001; HBV DNA clearance rate: χ~2= 75. 526,107. 412,and 38. 138,all P < 0. 001). The infants were evaluated at birth and at 6 and 12 months,and there were significant differences between the treatment group and the control group in HBsAg positive rate( χ~2= 6. 089,5. 074,and 5. 074,all P < 0. 05) and HBV DNA positive rate( χ~2= 5. 074,P < 0. 05). There was no significant difference in Apgar score between the two groups( P > 0. 05),and their growth and development indices were within normal ranges. Conclusion TDF administration in early pregnancy can help with the recovery of liver function and is safe and effective in blocking the mother-to-child transmission of HBV.
Objective To investigate the antiviral effect of tenofovir disoproxil( TDF) in women with chronic hepatitis B( CHB) and its effect in blocking mother-to-child transmission of CHB during early pregnancy. Methods A total of 164 pregnant women who were diagnosed with CHB in Nanchang Ninth Hospital from July 2014 to December 2016 were enrolled,and their neonates were also enrolled as subjects. According to their will,the patients were divided into treatment group with 80 patients and control group with 84 patients. The patients in the treatment group were given TDF 300 mg/d during early pregnancy,followed by antiviral therapy for CHB after delivery,and those in the control group did not receive antiviral therapy. All neonates were given hepatitis B immunoglobulin and hepatitis B vaccine after birth.The changes in liver and renal function,electrolytes,myocardial zymogram,routine blood and urine test results,HBV serum markers,and HBV DNA were observed,and adverse reactions were recorded. HBsAg and HBV DNA were measured for infants at birth and at 6 and 12 months after birth; HBV infection,growth and development,and complications were evaluated,and Apgar score was determined. The t-test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between groups. Results There were significant differences between the treatment group and the control group in alanine aminotransferase( ALT) normalization rate,and HBV DNA clearance rate at 18,24,and 36 weeks of pregnancy( ALT normalization rate: χ~2= 19. 145,24. 990,and 36. 414,all P < 0. 001; HBV DNA clearance rate: χ~2= 75. 526,107. 412,and 38. 138,all P < 0. 001). The infants were evaluated at birth and at 6 and 12 months,and there were significant differences between the treatment group and the control group in HBsAg positive rate( χ~2= 6. 089,5. 074,and 5. 074,all P < 0. 05) and HBV DNA positive rate( χ~2= 5. 074,P < 0. 05). There was no significant difference in Apgar score between the two groups( P > 0. 05),and their growth and development indices were within normal ranges. Conclusion TDF administration in early pregnancy can help with the recovery of liver function and is safe and effective in blocking the mother-to-child transmission of HBV.
引文
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[10] HU YH,YI W,LIU M,et al. Safety evaluation of telbivudine application throughout pregnancy in women with chronic hepatitis B[J]. J Clin Hepatol,2014,32(5):285-288.(in Chinese)胡玉红,易为,刘敏,等.慢性乙型肝炎妇女全孕期应用替比夫定的安全性研究[J].临床肝胆病杂志,2014,32(5):285-288.
[11] FU D,LIU M,YI W,et al. Safety and efficacy of tenofovir disoproxil in treatment of women with chronic hepatitis B during pregnancy[J]. ADRJ,2015,17(4):253-256.(in Chinese)付冬,刘敏,易为,等.替诺福韦酯用于慢性乙型肝炎患者妊娠期的有效性和安全性研究[J].药物不良反应杂志,2015,17(4):253-256.
[12] QI LY,ZHAO ZJ,LIU JQ. Clinical study on the effectiveness and mother-to-infant blocking transmission by tenofovir disoproxil in treatment of patients with chronic hepatitis B throughout pregnancy[J]. Chin J Med Guide,2017,19(2):176-177.(in Chinese)齐丽韫,赵志军,刘家群.替诺福韦酯治疗妊娠慢性乙型肝炎患者的疗效及母婴阻断的有效性研究[J].中国医药导刊,2017,19(2):176-177.
[2] PAN CQ,DUAN Z,DAI E,et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load[J]. N Engl J Med,2016,374(24):2324-2334.
[3] HYUN MH,LEE YS,KIM JH,et al. Systematic review with metaanalysis:The efficacy and safety of tenofovir to prevent motherto-child transmission of hepatitis B virus[J]. Aliment Pharmacol Ther,2017,45(12):1493-1505.
[4] VISVANATHAN K,DUSHEIKO G,GILES M,et al. Paper produced by Australian,UK and New Zeal and key opinion leaders[J]. Gut,2016,65(2):340-335.
[5] GILES ML,VISVANATHAN K,LEWIN SR,et al. Chronic hepatitis B infection and pregnancy[J]. Obstet Gynecol Surv,2012,67(1):37-44.
[6] WANG C,WU X,WANG C,et al. Blocking effects on and influencing factors for mother-to-infant transmission of hepatitis B virus:A study in Changchun,China[J]. J Clin Hepatol,2015,31(8):1238-1243.(in Chinese)王川,武兴,王崇,等. HBV母婴传播阻断效果及影响因素分析[J].临床肝胆病杂志,2015,31(8):1238-1243.
[7] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Society of Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A2015 update[J]. J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[8] European Association for the Study of the Liver. EASL 2017clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol,2017.[Epub ahead of print]
[9] Committee of Experts on Clinical Treatment of Tenofovir Disoproxil. Experts consensus on clinical treatment of tenofovir disoproxil in patients with chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis:Electronic Edition,2015,9(1):120-125.(in Chinese)替诺福韦酯治疗慢性HBV感染临床应用专家委员会.替诺福韦酯治疗慢性HBV感染临床应用专家共识[J/CD].中华实验和临床感染病杂志:电子版,2015,9(1):120-125.
[10] HU YH,YI W,LIU M,et al. Safety evaluation of telbivudine application throughout pregnancy in women with chronic hepatitis B[J]. J Clin Hepatol,2014,32(5):285-288.(in Chinese)胡玉红,易为,刘敏,等.慢性乙型肝炎妇女全孕期应用替比夫定的安全性研究[J].临床肝胆病杂志,2014,32(5):285-288.
[11] FU D,LIU M,YI W,et al. Safety and efficacy of tenofovir disoproxil in treatment of women with chronic hepatitis B during pregnancy[J]. ADRJ,2015,17(4):253-256.(in Chinese)付冬,刘敏,易为,等.替诺福韦酯用于慢性乙型肝炎患者妊娠期的有效性和安全性研究[J].药物不良反应杂志,2015,17(4):253-256.
[12] QI LY,ZHAO ZJ,LIU JQ. Clinical study on the effectiveness and mother-to-infant blocking transmission by tenofovir disoproxil in treatment of patients with chronic hepatitis B throughout pregnancy[J]. Chin J Med Guide,2017,19(2):176-177.(in Chinese)齐丽韫,赵志军,刘家群.替诺福韦酯治疗妊娠慢性乙型肝炎患者的疗效及母婴阻断的有效性研究[J].中国医药导刊,2017,19(2):176-177.