HBeAg阳性慢性乙型肝炎孕妇替比夫定治疗前后血清Th1/Th2型细胞因子的水平变化

黄鸿菲; 何登明; 吴全新; 李茂仕; 朱鹏; 王宇明

doi:10.3969/j.issn.1001-5256.2014.06.011

HBeAg阳性慢性乙型肝炎孕妇替比夫定治疗前后血清Th1/Th2型细胞因子的水平变化

DOI: 10.3969/j.issn.1001-5256.2014.06.011

1. 第三军医大学西南医院全军感染病研究所感染病研究重庆市重点实验室
2. 蚌埠医学院
3. 解放军第88医院全军肝病诊治中心

基金项目:

国家自然科学基金面上项目(81270563)；

详细信息

中图分类号: R714.251
计量
- 文章访问数: 2145
- HTML全文浏览量: 20
- PDF下载量: 634
- 被引次数: 0
出版历程
- 收稿日期: 2013-10-18
- 出版日期: 2014-06-20

Changes in serum levels of Th1 /Th2 cytokines in HBeAg- positive pregnant women with HBV infection after telbivudine treatment

Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University

Research funding:

摘要

摘要: 目的通过观察慢性HBV感染孕妇替比夫定治疗前后血清Th1/Th2型细胞因子水平变化,探讨替比夫定阻断HBV母婴传播的免疫机制。方法对2008年4月至2012年9月收治的HBeAg阳性慢性HBV感染孕妇54例进行回顾分析,根据ALT水平分为免疫活化组（n=18）和免疫耐受组（n=36）,于妊娠中晚期给予替比夫定600 mg/d,常规检测治疗前、分娩前血清ALT、TBil、HBV DNA水平及HBV标志物变化情况,酶联免疫吸附测定法检测Th1型细胞因子[白细胞介素（IL）2、干扰素（IFN）γ]和Th2型细胞因子（IL-4、IL-6）水平。正态分布的计量资料采用t检验,非正态分布的采用非参数检验。以Bivariate分析两变量相关性,用Pearson相关系数表示相关性。结果替比夫定治疗后血清HBV DNA水平明显下降（P<0.01）,ALT、TBil水平均无显著变化,无HBeAg血清学转换。相较于健康人群,2组在治疗前和分娩前均表现为IL-2（健康人群<4 pg/ml）和IFNγ（健康人群<15 pg/ml）高表达,而IL-4（健康人群<10 pg/ml）和IL-6...
- 乙型肝炎,慢性 /
- 干扰素类 /
- 白细胞介素类 /
- 替比夫定 /
- 孕妇
Abstract: Objective To evaluate the changes in serum levels of Th1 /Th2 cytokines in pregnant women with chronic hepatitis B virus ( HBV) infection after telbivudine treatment and to investigate the immune mechanism by which telbivudine blocks the mother- to- infant transmission of HBV. Methods Fifty- four HBeAg- positive pregnant women with chronic HBV infection were enrolled from April 2008 to September 2012, and they were divided into two groups based on their alanine aminotransferase ( ALT) levels: immune active group ( n =18) and immune tolerant group ( n = 36) . Telbivudine was administrated at a dose of 600 mg per day during the second or third trimester.Before treatment and prior to delivery, the serum levels of ALT, total bilirubin ( TBil) , HBV DNA, and HBV markers were routinely measured, and the levels of Th1 cytokines ( interleukin- 2 ( IL- 2) , interferon- γ ( IFNγ) ) and Th2 cytokines ( interleukin- 4 ( IL- 4) , interleukin- 6 ( IL- 6) ) were determined by enzyme- linked immunosorbent assay. SPSS 18. 0 was used for statistical analysis. Results After treatment, HBV DNA level was reduced significantly ( P < 0. 01) , while there were no significant changes in serum ALT and TBil and no HBeAg seroconversion. Compared with the healthy population, before treatment and prior to delivery, both treatment groups showed higher expression of IL- 2 ( healthy control < 4 pg /ml) and IFNγ ( healthy control < 15 pg /ml) but lower expression of IL- 4 ( healthy control< 10 pg /ml) and IL- 6 ( healthy control < 5 pg /ml) . Furthermore, there were no significant differences in IL- 2, IFNγ, IL- 4, and IL-6 levels between the two groups ( P > 0. 01) . Prior to delivery, IL- 4 level was elevated in immune active group ( P = 0. 014) , but within the limits of normal range, while IL- 2, IFNγ, and IL- 6 levels showed no significant changes ( P = 0. 182, 0. 259, and 0. 710, respectively) ; the levels of IL- 2, IFNγ, IL- 4, and IL- 6 in immune tolerant group showed no significant changes ( P = 0. 651, 0. 839, 0. 650, and 0. 542, respectively) . Conclusion Th1 cytokines are highly expressed while Th2 cytokines are lowly expressed in the second or third trimester among HBV- infected pregnant women. Short- term telbivudine treatment has limited influence on Th1 /Th2 balance in HBV- infected pregnant women, indicating that other mechanisms might be recruited for interfering with the mother- infant transmission of HBV.
- hepatitis B, chronic /
- interferons /
- interleukins /
- telbivudine /
- pregnant women

HTML全文

参考文献(24)

[1]HUANG RH, JIANG L, ZHANG K, et al.Adiponectin and its receptors in chronic Hepatitis B patients with metabolic syndrome[J].Int J Virol, 2013, 20 (3) :100-105. (in Chinese) 黄容海, 蒋力, 张珂, 等.血清脂联素水平与慢性乙型肝炎患者伴发代谢综合征的相关性研究[J].国际病毒学杂志, 2013, 20 (3) :100-105.

[2] NGUYEN G, GARCIA RT, NGUYEN N, et al.Clinical course of hepatitis B virus infection during pregnancy[J].Aliment Pharmacol Ther, 2009, 29 (7) :755-764.

[3]PAN CQ, ZOU HB, CHEN Y, et al.Cesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants[J].Clin Gastroenterol Hepatol, 2013, 11 (10) :1349-1355.

[4]SHAO ZJ, ZHANG L, XU JQ, et al.Mother-to-infant transmission of hepatitis B virus:a Chinese experience[J].J Med Virol, 2011, 83 (5) :791-795.

[5]PAN CQ, LEE HM.Antiviral therapy for chronic hepatitis B in pregnancy[J].Semin Liver Dis, 2013, 33 (2) :138-146.

[6]HAN GR, CAO MK, ZHAO W, et al.A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection[J].J Hepatol, 2011, 55 (6) :1215-1221.

[7]ZENG ZL, WU JL, WU JZ.Detection of proportions of lymphocyte T subsets in peripheral blood and levels of Th1/Th2 cytokines in patients with hepatitis B virus infection and its clinical significance[J].J Jilin Univ:Med Edit, 2012, 38 (3) :555-558. (in Chinese) 曾志励, 吴健林, 吴继周.乙型肝炎患者外周血T淋巴细胞亚群比例和Th1/Th2细胞因子水平检测及其临床意义[J].吉林大学学报:医学版, 2012, 38 (3) :555-558.

[8]ZHU B, ZHANG P, WANG TB, et al.Measurement of Th1/Th2cytokine levels in chronic hepatitis B during telbivudine therapy[J].J Clin Hepatol, 2009, 25 (6) :415-417. (in Chinese) 朱斌, 张平, 王天宝, 等.替比夫定治疗慢性乙肝血清Th1/Th2亚群细胞因子的水平变化[J].临床肝胆病杂志, 2009, 25 (6) :415-417.

[9]BETZ AG.Immunology:tolerating pregnancy[J].Nature, 2012, 490:47-48.

[10] Chinese Society of Hepatology, Chinese Society of Infectious Diseases, Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B (2010 version) [J].J Clin Hepatol, 2011, 27 (1) :Ⅰ-ⅩⅥ. (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 (2010年版) [J].临床肝胆病杂志, 2011, 27 (1) :Ⅰ-ⅩⅥ.

[11]van ZONNEVELD M, van NUNEN AB, NIESTERS HG, et al.Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection[J].J Viral Hepat, 2003, 10 (4) :294-297.

[12]SUN WH, CHU LL, LIU WL, et al.Efficacy and safety of telbivudine in preventing mother-to-infant transmission of HBV in pregnant women with high HBV DNA load[J].J Clin Hepatol, 2013, 29 (8) :596-599. (in Chinese) 孙维会, 初蕾蕾, 柳维林, 等.替比夫定阻断HBV DNA高载量孕妇母婴传播的疗效和安全性观察[J].临床肝胆病杂志, 2013, 29 (8) :596-599.

[13]CHEN XQ, YAO ZC, WU LP, et al.Clinical study on telbivudine in preventing mother-to-infant HBV transmission during the late pregnancy[J].J Clin Hepatol, 2011, 27 (12) :1282-1284. (in Chinese) 陈晓勤, 姚展成, 吴丽萍, 等.妊娠晚期应用替比夫定阻断乙型肝炎病毒垂直传播的临床观察[J].临床肝胆病杂志, 2011, 27 (12) :1282-1284.

[14]MA L, CAI YJ, YU L, et al.Treatment with telbivudine positively regulates antiviral immune profiles in Chinese patients with chronic hepatitis B[J].Antimicrob Agents Chemother, 2013, 57 (3) :1304-1311.

[15]CHEN Y, LI X, YE B, et al.Effect of telbivudine therapy on the cellular immune response in chronic hepatitis B[J].Antiviral Res, 2011, 91 (1) :23-31.

[16]HAY JE.Liver disease in pregnancy[J].Hepatology, 2008, 47 (3) :1067-1076.

[17] PASQUETTO V, WIELAND SF, UPRICHARD SL, et al.Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures[J].J Virol, 2002, 76 (11) :5646-5653.

[18]LIN SJ, SHU PY, CHANG C, et al.IL-4 suppresses the expression and the replication of hepatitis B virus in the hepatocellular carcinoma cell line Hep3B[J].J Immunol, 2003, 171 (9) :4708-4716.

[19]YAO Y, LI J, LU Z, et al.Proteomic analysis of the interleukin-4 (IL-4) response in hepatitis B virus-positive human hepatocelluar carcinoma cell line HepG2.2.15[J].Electrophoresis, 2011, 32 (15) :2004-2012.

[20]KUO TM, HU CP, CHEN YL, et al.HBV replication is significantly reduced by IL-6[J].J Biomed Sci, 2009, 16:41.

[21]YUE L, TANJY, LI SH, et al.Research advances in mechanisms of immune tolerance during pregnancy[J].Maternal Child Health Care China, 2012, 27 (5) :784-786. (in Chinese) 岳兰, 谭继英, 李少红, 等.妊娠免疫耐受机制的研究进展[J].中国妇幼保健, 2012, 27 (5) :784-786.

[22]GAO YQ, SUN XH, ZHANG XY, et al.Study of different immune status among various types of chronic HBV infectors[J].Chin J Gastroenterol Hepatol, 2005, 14 (1) :82-86. (in Chinese) 高月求, 孙学华, 章晓鹰, 等.不同类型慢性乙肝病毒感染者外周血细胞因子表达的差异[J].胃肠病学和肝病学杂志, 2005, 14 (1) :82-86.

[23]CHEN KH, JIANG XH, PU YC, et al.The developmental observe of Th1/Th2-type cytokines in peripheral blood in patients with chronic hepatitis B[J].Chin J Clin Gastroenterol, 2006, 18 (6) :345-347. (in Chinese) 陈凯红, 蒋祥虎, 蒲云川, 等.慢性乙肝患者外周血Th1 Th2类细胞因子变化的动态观察[J].临床消化病杂志, 2006, 18 (6) :345-347.

[24]JIANG XN, SHI KS, LI DZ, et al.Efficacy and safety of telbivudine using in pregnant patients with chronic HBV infection[J].J Med Res, 2012, 41 (7) :172-174. (in Chinese) 姜秀浓, 施凯舜, 李德周, 等.替比夫定治疗慢性HBV感染孕妇的疗效和安全性观察[J].医学研究杂志, 2012, 41 (7) :172-174.

施引文献

资源附件(0)

访问统计