收稿日期: 2013-08-16
修回日期: 2013-10-25
网络出版日期: 2014-07-15
基金资助
国家自然科学基金（11075207）和深圳市科技局科技计划项目（201003431）资助
Effects of anti-hepatitis B virus drugs on sperm quality of patients with chronic hepatitis B
Received date: 2013-08-16
Revised date: 2013-10-25
Online published: 2014-07-15
比较研究抗乙肝病毒药物干扰素、拉米夫定和阿德福韦酯对育龄慢性乙肝男性患者精子质量的影响.将90名20~45岁男性育龄慢性乙肝患者，随机分为干扰素治疗组、拉米夫定治疗组和阿德福韦酯治疗组.分别检测各药物组患者治疗前、治疗中和治疗后的血清HBsAg阴转率、HBeAg阴转率、抗-HBe阴转率、乙肝病毒-DNA（HBV-DNA）和谷丙转氨酶（ALT）以及精子的密度和活力.结果发现，干扰素、拉夫米定、阿德福韦酯治疗慢性乙肝的疗效显著，但治疗期间和停药3个月后，各组患者的精子密度和活力水平均显著下降（P<0.05；P<0.01），停药6个月后恢复至治疗前的水平.结果提示，干扰素、拉夫米定、阿德福韦酯均明显降低男性患者精子密度和活力的水平，影响到患者的生育力；停药后，该副作用有所缓解.
宋丹 , 李凌伟 , 田菁燕 , 甘菲菲 , 王箭 , 韩睿 , 张芳 . 抗乙肝病毒药物对慢性乙肝育龄患者精子质量的影响[J]. 中国科学院大学学报, 2014 , 31(4) : 460 -465 . DOI: 10.7523/j.issn.2095-6134.2014.04.003
The aim of this study was to investigate the effects of interferon, lamivudine, and adefovir on sperm quality in patients with chronic hepatitis B. A total of 90 patients with HBeAg-positive chronic hepatitis B were randomly divided into interferon-treated group, lamivudine-treated group, and adefovir-treated group. HBsAg, HBeAg, and Anti-HBe serum conversion rates, serum HBV-DNA, and alanine aminotransferase (ALT) levels in serum were measured. In addition the density and motility of sperm in these patients were also measured 6 months ofter drug with drawal. The results show that the density and motility of sperm significantly decreased in all the groups (P<0.05;P<0.01). This impairment on sperm quality was improved 6 months after drug withdrawal. The results suggest that the adverse effects of anti-hepatitis B drugs on sperm quality in chronic hepatitis B patients at reproductive age should be considered.
Key words： chronic hepatitis B; interferon; lamivudine; adefovir; sperm quality
[1] Liaw Y F, Chu C M. Hepatitis B virus infection [J]. Lancet, 2009, 373(9663): 582-592.
[2] Zhang Y, Zhang H, Elizabeth A, et al. Epidemiology of hepatitis B and associated liver diseases in China [J]. Chinese Medical Science Journal, 2012. 27(4): 243-248.
[3] Liang X, Bi S, Yang W, et al. Reprint of: Epidemiological serosurvey of hepatitis B in China-declining HBV prevalence due to hepatitis B vaccination [J]. Vaccine, doi: 10.1016/j.vaccine.2013.08.012.
[4] Zhou X P, Hu X L, Zhu Y M, et al. Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B [J]. Asian Journal of Andrology, 2011, 13: 465-469.
[5] Oger P, Yazbeck C, Gervais A, et al. Adverse effects of hepatitis B virus on sperm motility and fertilization ability during IVF [J]. Reproductive BioMedicine Online, 2011, 23: 207-212.
[6] Pirwany I R, Phillips S, Kelly S, et al. Reproductive performance of couples discordant for hepatitis B and C following IVF treatment [J]. Journal of Assisted Reproduction Genetics, 2004, 21(5): 157-161.
[7] Huang J M, Huang T H, Qiu H Y, et al. Effects of hepatitis B virus infection on human sperm chromosomes [J]. World Journal of Gastroenterology, 2003, 9(4): 736-740.
[8] Vicari E, Arcoria D, Di Mauro C, et al. Sperm output in patients with primary infertility and hepatitis B or C virus; negative influence of HBV infection during concomitant varicocele [J]. Minerva Medica, 2006, 97(1): 65-77.
[9] Lorusso F, Palmisano M, Chironna M, et al. Impact of chronic viral diseases on semen parameters [J]. Andrologia, 2010, 42(2): 121-126.
[10] Moretti E, Federico M G, Giannerini V, et al. Sperm ultrastructure and meiotic segregation in a group of patients with chronic hepatitis Band C [J]. Andrologia, 2008, 40(5): 286-291.
[11] Zhu Y Y, He Y K. Mechanisms of the actions of interferons [J]. Chinese Journal of Hepatology, 2007, 15(11): 845-846 (in Chinese). 朱幼英, 贺玉凯. 干扰素的作用机制 [J]. 中华肝脏病杂志, 2007, 11: 845-846.
[12] Yao G B, Alison T M, Huang Y, et al. Evaluation of health related quality of life with treatment of lamivudine in chronic hepatitis B patients [J]. Chinese Hepatology, 2003, 8(4): 3-5 (in Chinese). 姚光弼, Alison T M, 黄瑛,等. 拉米夫定治疗慢性乙型肝炎生存质量评价 [J]. 肝脏, 2003, 8: 3-5.
[13] 芦红. 抗乙肝病毒药物的药用临床研究进展[J]. 中国中医药咨讯, 2011, 3(15): 78.
[14] 徐道振, 巫善明, 周霞秋,等. 病毒性肝炎临床实践[J]. 北京: 人民卫生出版社, 2006.
[15] 王慈, 张清月, 张鑫. 病毒性肝炎抗病毒治疗进展 [J]. 中国实用医药, 2009, 4(15): 232-235.
[16] Estrada L S, Champion H C, Wang R, et al. Effect of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human sperm motility, viability and motion parameters [J]. International Journal of Andrology, 1997, 20(4): 237-242.
[17] Fedder J, Ellerman-Eriksen S. Effect of cytokines on sperm motility and ionophore-stimulated acrosome reaction [J]. Archives of Andrology, 1995, 35(3): 173-185.
[18] Zhou X L, Sun P N, Huang T H, et al. Effects of hepatitis B virus S protein on human sperm function [J]. Human Reproduction, 2009, 24(7): 1575-1583.
[19] Liu J L, Luo M, Xiong G B. Correlative analysis between sperm morphology and sperm vitality [J]. Modern Diagnosis & Treatment, 2009, 20(2): 71-72 (in Chinese). 刘居理, 罗明, 熊国保. 精子形态与精子活力的相关分析[J]. 现代诊断与治疗, 2009, 20(2): 71-72.
[20] 钟石英,曾伟强,邓小梅. 干扰素与阿德福韦酯治疗慢性乙型肝炎的效果比较 [J]. 实用医学杂志, 2011, 27(14): 2644-2645.
[21] Yao G B, Wang B E, Cui Z Y, et al. A randomized double-blind, placebo-controlled study of lamivudine in treatment of chronic hepatitis B patients[J]. Chinese Journal of New Drugsand Clinical Remedies, 1999, 18(3): 131-135 (in Chinese). 姚光弼, 王宝恩, 崔振宇, 等. 拉米夫定治疗中国人慢性乙型肝炎的双盲安慰剂、随机对照研究 [J]. 中国新药与临床杂志, 1999, 18(3): 131-135.
[22] Ginaburg ES, Xiao L, Gargiulo AR, et al. T-Helper 2 and 3 type immunity to trophoblast in successful in vitro fertilization-embryo transfer [J]. Fertility and Sterility, 2005. 83(6): 1659-1664.
[23] Zheng L H, Yang D, Gao X Q. Correlation of concentration of nitric oxide in male semen with male infertility [J].Chinese Journal of Anatomy, 2009, 32(5): 623-625 (in Chinese). 郑立宏, 杨丹, 高晓勤. 人精液一氧化氮含量与男性不育的相关性 [J]. 解剖学杂志, 2009, 32(5): 623-625.
[24] De Jonge C. Biological basis for human capacitation [J]. Human Reproduction Update, 2005, 11(3): 205-214.
[25] Yang L H, Jiang Y A, Chen X B. Study on combination therapy of alpha interferon with Lamivudine inhibits HBV replication. [J]. Chinese Journal of Biochemical Pharmaceutics, 2001, 22(1): 42-43 (in Chinese). 杨丽华, 江应安, 陈晓蓓. α-干扰素联合拉米夫定抗乙型肝炎病毒复制的临床研究 [J]. 中国生化药物杂志, 2001, 22(1): 42-43.
[26] Yuan H N, Luo G H, Deng Y M. Effect of combination treatment of Adefovir and γ-IFN to the hepatic fibrosis caused by hepatitis B [J]. Journal of Clinical Hepatology, 2008, 24(4): 254-255 (in Chinese). 袁海宁, 罗光汉, 邓一鸣. 阿德福韦酯联合γ-干扰素对慢性乙型肝炎肝纤维化指标的影响 [J]. 临床肝胆病杂志, 2008, 24(4): 254-255.
[27] Yang Z G, Li Y F, Zhang L, et al. Clinical effecttivess of adefovir dipivoxil combined with Lamivudine for short application to patients with chronic hepatitis B [J]. Progress in Modern Biomedicine, 2012, 12(6): 1146-1149 (in Chinese). 杨智刚, 李勇富, 张流, 等. 阿德福韦酯短程联合拉米夫定治疗慢性乙型肝炎疗效分析 [J].现代生物医学进展, 2012, 12(6): 1146-1149.
/
| 〈 |
|
〉 |
