产妇富马酸替诺福韦酯在中断母亲向婴儿传播乙肝病毒的疗

StephenW

Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus

    Huey-Ling Chen1,2,3, Chien-Nan Lee4, Chin-Hao Chang5, Yen-Hsuan Ni1, Ming-Kwang Shyu3, Shih-Ming Chen7, Jen-Jan Hu8, Hans Hsienhong Lin9, Lu-Lu Zhao10, Shu-Chi Mu11, Ming-Wei Lai12, Chyi-Long Lee13, Hsien-Ming Lin14, Ming-Song Tsai15, Jenn-Jeih Hsu16, Ding-Shinn Chen3,6,17, K. Arnold Chan5, Mei-Hwei Chang1,3,* andTaiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT Study)

Article first published online: 13 MAY 2015

DOI: 10.1002/hep.27837

© 2015 by the American Association for the Study of Liver Diseases

Issue
Hepatology
Hepatology

Volume 62, Issue 2, pages 375–386, August 2015
Article has an altmetric score of 9


    Potential conflict of interest: Dr. M.-H. Chang received grants from Gilead.

    Supported by grants from the Center of Disease Control and the Ministry of Health and Welfare, Taiwan, and from Gilead Sciences, Inc. (Foster City, CA).

    Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT Study): In addition to the authors, members of the Taiwan Study Group for the PreMIT Study include the following: Dr. Hsiao-Lin Hwa, Dr. Yi-Ning Su, Dr. Jin-Chung Shih, Dr. Kuang-Han Chao, Department of Obstetrics & Gynecology; Dr. Jia-Feng Wu, Dr. Hong-Yuan Hsu, Department of Pediatrics; Dr. Chun-Jen Liu, Dr. Tung-Hung Su, Department of Internal Medicine, National Taiwan University Hospital; Dr. Chin-Chuan Lin, Pei-Ying Lin, Wen-Rong Yang, Department of Obstetrics & Gynecology, Taiwan Adventist Hospital; Dr. Chun-Kuang Yang, Dr. Yin-Kuang Chang, Dr. Kuo-Hu Chen, Department of Obstetrics & Gynecology, Taipei Tzu Chi Hospital; Dr. Yu-Hung Lin, Dr. Heng-Ju Chen, Dr. Hun-Shan Pan, Department of Obstetrics & Gynecology; Dr. Beng-Huat Lau, Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital; Dr. Po-Jen Cheng, Dr. Yao-Lung Chang, Dr. Ho-Yen Chiueh, Dr. Tzu-Hao Wang, Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital, Linkou; Dr. Liang-Ming Lo, Dr. Chia-Lin Hsieh, Department of Obstetrics & Gynecology; Dr. Shao-Wen Cheng, Department of Pediatrics, Chang Gung Memorial Hospital, Taipei; Dr. Lung-Huang Lin, Department of Pediatrics, Cathay General Hospital, Taipei; Dr. Bo-Qing She, Department of Obstetrics & Gynecology; Dr. King-Jun Koh, Dr. Yi-Li Hung, Department of Pediatrics, Sijhih Cathay General Hospital; Dr. Fu-Shiang Peng, Department of Obstetrics & Gynecology; Dr. Yu-Cheng Lin, Department of Pediatrics, Far Eastern Memorial Hospital; Dr. Tzee-Chung Wu, Department of Pediatrics; Dr. Chih-Yao Chen, Department of Obstetrics & Gynecology, Taipei Veterans General Hospital; Dr. Chie-Pein Chen, Dr. Jian-Pei Huang, Department of Obstetrics & Gynecology; Dr. Chun-Yan Yeung, Department of Pediatrics, MacKay Memorial Hospital, Taipei; Chen-Ju Lin, Department of Obstetrics & Gynecology, MacKay Memorial Hospital, Tamsui; Dr. Wei-Tsung Chiu, Dr. Duo-Sheng Wang, Department of Obstetrics & Gynecology; Dr. Wen-Terng Lin, Department of Pediatrics, En Chu Kong Hospital; Dr. Kwei-Shuai Hwang, Department of Obstetrics & Gynecology, Tri-Service General Hospital; Dr. Ching-Feng Huang, Department of Pediatrics, Tri-Service General Hospital.

The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen–positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375–386

StephenW

产妇富马酸替诺福韦酯在中断母亲向婴儿传播乙肝病毒的疗效

    休伊灵Chen1,2,3，建南Lee4，展灏Chang5，颜轩NI1，明KWANG Shyu3，施明Chen7，仁扬Hu8，汉斯Hsienhong Lin9，路路Zhao10，Shu-智Mu11，明伟Lai12，齐豫龙Lee13，献明Lin14，明宋Tsai15，爵Jeih Hsu16，鼎希恩Chen3,6,17，K.阿诺德Chan5，美Hwei Chang1,3，*预防乙肝病毒的母亲向婴儿传播和台湾研究小组（PreMIT研究）

文章首次在线发表：2015年5月13日

DOI：10.1002 / hep.27837

©2015年肝病研究的美国协会

问题
肝病
肝病

第62卷，第2期，页375-386，2015年8月
文章有altmetric比分9


    潜在的利益冲突：M.-H.博士常收到赠款基列。

    由疾病控制中心和卫生和福利，台湾省，并从吉利德科学公司（福斯特市，CA）的资助。

    预防乙肝病毒（PreMIT研究）的母亲向婴儿传播台湾研究小组：除了作者，台湾研究小组的研究PreMIT成员包括：博士萧敬腾林华，易博士-Ning苏，博士金涌施，匡汉超博士，妇产科学系;佳吴锋博士，博士宏远许，儿科系;骏仁Liu博士，博士东红素，内科，台大医院系;博士展穿林，佩萤蔺，文荣阳，妇产科，台安医院的部门;博士春匡阳，博士荫林光常博士郭台胡琛，妇产科，台北慈济医院部;博士玉洪麟，博士恒巨臣博士浑山潘妇产科学系;博士绷-发先生刘儿科系，新光吴火狮纪念医院;博士宝仁诚，博士耀隆畅，何博士颜Chiueh，博士姿王浩，妇产科，长庚医院，林口部;博士梁明螺，嘉林谢医师，妇产科学系;博士绍文成，儿科，长庚医院，台北部;博士龙黄林，儿科，国泰医院，台北部;博士柏清她，妇产科学系;博士王君岛，益厉红博士，儿科，汐止国泰医院系;博士傅鹏史昂，妇产科学系;博士玉程琳，儿科，远东纪念医院的部门; Tzee涌吴医生，儿科系;博士芷姚晨，妇产科，台北荣民总医院系;博士千绘-P​​EIN陈鉴黄培博士，妇产科学系;博士春燕杨，儿科，马偕医院，台北部;陈举林，妇产科，马偕医院，淡水系;魏聪博士邱，多生Wang博士，妇产科学系;博士文腾麟，儿科，恩珠江医院部;博士桂帅黄某，妇产科，三军总医院的部门;清丰黄医生，儿科系，三军总医院。

疗效和产妇富马酸替诺福韦酯（TDF）减少母亲向婴儿乙肝病毒（HBV）的传输安全性尚不清楚。我们进行了一项前瞻性，多中心临床试验，并参加118乙肝表面抗原（HBsAg） - 和乙肝e抗原阳性的孕妇与HBV DNA≥7.5日志10 IU / mL的。母亲没有接受药物治疗（对照组，n = 56，HBV DNA 8.22±0.39日志10 IU / mL）或TDF 300毫克，每天（TDF组，n = 62，HBV DNA 8.18±0.47日志10 IU / mL）的从30-32孕周，直到产后1个月。主要成果是HBsAg的婴儿在6个月大。在交付时，TDF组低产妇HBV DNA水平（4.29±0.93 8.10与0.56±日志10 IU / mL时，P <0.0001）。在一百二十三分之一百二十一新生儿中，TDF集团在6个月大（1.54％和10.71％，P = 0.0481），出生时（6.15％和31.48％，P = 0.0003）和乙肝表面抗原阳性的HBV DNA阳性率较低。多因素分析表明，TDF组风险较低（比值比= 0.10，P = 0.0434）和羊膜穿刺术与婴儿的HBsAg阳性的风险较高（比值比6.82，P = 0.0220）有关。在TDF组的母体丙氨酸转氨酶（ALT）水平高于正常为≥3个月两次上限（3.23％比14.29％，P = 0.0455），谷丙转氨酶的产后升高的程度较轻的发生率较低（P = 0.007 ）和ALT的较低速率超过正常产后2个月的五倍的上限值（1.64％和14.29％，P = 0.0135）。产妇肌酸酐和肌酐激酶水平，先天性异常，早产，和在婴儿的生长参数的率可比两组。在12个月，1 TDF-组子新开发的HBsAg阳性，大概是由于产后感染和低效体液应答疫苗。结论：治疗TDF对高病毒血症的母亲出生时，婴儿的HBsAg阳性6个月的婴儿降低HBV DNA和改善产妇ALT升高。 （肝病2015; 62：375-386