恩替卡韦对慢性乙肝患者血清中HBV DNA载量与TGF-β1的影响
摘要
目的：观察慢性乙肝患者经恩替卡韦治疗前后乙肝病毒载量(HBV DNA)与血清中TGF-β1变化,分析其疗效,为临床合理应用恩替卡韦治疗慢性乙肝提供参考。方法：按随机原则选取63例恩替卡韦试验组及对照组的慢性乙肝患者。试验组33例,其中轻度患者9例、中度患者17例、重度患者7例,分别口服恩替卡韦0.5mg每日一次,同时加用一般护肝药；对照组30例,其中轻度患者13例、中度患者12例、重度患者5例,单用一般护肝药。分别在治疗前、治疗3个月、治疗6个月收集血清,检测血清中HBV DNA、TGF-β1的含量,观察其变化。以HBV DNA载量与TGF-β1为主要指标,采用SPSS13.0系统软件进行统计分析,比较治疗前后两者的变化。结果：恩替卡韦试验组轻度、中度和重度患者血清中HBV DNA载量治疗后呈下降趋势,治疗3月、6月与治疗前比较(P<0.05)有统计学差异。试验组中度和重度患者血清TGF-β1水平治疗后呈下降趋势,重度患者治疗6月与治疗前比较(P<0.05)有统计学差异。试验组与对照组(轻度、中度、重度患者)血清中HBV DNA载量在治疗6月比较(P<0.05)有统计学差异。试验组与对照组(重度患者)血清TGF-β1水平治疗6月相比(P<0.05)有统计学差异。结论：恩替卡韦对慢性乙肝血清中的TGF-β1与乙肝病毒载量(HBV DNA)有影响,慢性乙肝轻度、中度及重度患者经恩替卡韦治疗后血清中的HBV DNA载量明显下降,同时慢性乙肝重度患者血清中的TGF-β1水平明显下降。慢性乙肝重度患者经恩替卡韦治疗后效果较好。
Objective:To investigate hepatitis B viral load(HBV DNA) and serum TGF-β1 changes in chronic hepatitis B patients before and after entecavir treatment,to understand the effect of entecavir, in order to provide a reference the clinical application of entecavir treat chronic hepatitis B.Methods:There are enticavir test group and control group who 63 cases with chronic hepatitis B patients are selected randomly.Test group 33 cases,including 9 cases of mild,17 cases of moderate,7 cases of severe patients.Entecavir 0.5mg once a day,while the general hepatoprotective drug are given;Control group 30 cases, including 13 cases of mild,12 cases of moderate,5 cases of severe patients.The general hepatoprotective drug are given. To observe the changes in Serum HBV DNA and TGF-(31 when be prepared treatment,treatment in 3 months,in 6 months respectively. With hepatitis B viral load and TGF-β1 as the main indicators used SPSS13.0 system software for statistical analysis,comparing between the changes before and after treatment.Results:Entecavir test group includ chronic hepatitis B mild, moderate and severe patients whoes Serum HBV DNA are decreased. There are statistically significant difference in Serum HBV DNA that compare treatment in 3 months and in 6 months with be prepared treatment (p<0.05). Entecavir test group includ chronic hepatitis B moderate and severe patients whoes serum TGF-β1 are decreased. There are statistically significant difference in chronic hepatitis B severe patients whoes serum TGF-β1 that compare treatment in 6 months with be prepared treatment(p<0.05). There are statistically significant difference in test group and control group (chronic hepatitis B mild, moderate and severe patients) of serum HBV DNA comparison when they are treatment in 6 months(p<0.05). There are statistically significant difference in test group and control group that chronic hepatitis B severe patients of serum TGF-β1 comparison when they are treatment in 6 months (p<0.05).Conclusions:Entecavir have influence on chronic hepatitis B patients of serum HBV DNA and TGF-β1 levels.There are a significant decreased in chronic hepatitis B mild,moderate and severe patients of serum HBV DNA. There are a significant decrease in chronic hepatitis B severe patients of serum TGF-β1. The chronic hepatitis B severe patients treated by enticavir is better.
Objective:To investigate hepatitis B viral load(HBV DNA) and serum TGF-β1 changes in chronic hepatitis B patients before and after entecavir treatment,to understand the effect of entecavir, in order to provide a reference the clinical application of entecavir treat chronic hepatitis B.Methods:There are enticavir test group and control group who 63 cases with chronic hepatitis B patients are selected randomly.Test group 33 cases,including 9 cases of mild,17 cases of moderate,7 cases of severe patients.Entecavir 0.5mg once a day,while the general hepatoprotective drug are given;Control group 30 cases, including 13 cases of mild,12 cases of moderate,5 cases of severe patients.The general hepatoprotective drug are given. To observe the changes in Serum HBV DNA and TGF-(31 when be prepared treatment,treatment in 3 months,in 6 months respectively. With hepatitis B viral load and TGF-β1 as the main indicators used SPSS13.0 system software for statistical analysis,comparing between the changes before and after treatment.Results:Entecavir test group includ chronic hepatitis B mild, moderate and severe patients whoes Serum HBV DNA are decreased. There are statistically significant difference in Serum HBV DNA that compare treatment in 3 months and in 6 months with be prepared treatment (p<0.05). Entecavir test group includ chronic hepatitis B moderate and severe patients whoes serum TGF-β1 are decreased. There are statistically significant difference in chronic hepatitis B severe patients whoes serum TGF-β1 that compare treatment in 6 months with be prepared treatment(p<0.05). There are statistically significant difference in test group and control group (chronic hepatitis B mild, moderate and severe patients) of serum HBV DNA comparison when they are treatment in 6 months(p<0.05). There are statistically significant difference in test group and control group that chronic hepatitis B severe patients of serum TGF-β1 comparison when they are treatment in 6 months (p<0.05).Conclusions:Entecavir have influence on chronic hepatitis B patients of serum HBV DNA and TGF-β1 levels.There are a significant decreased in chronic hepatitis B mild,moderate and severe patients of serum HBV DNA. There are a significant decrease in chronic hepatitis B severe patients of serum TGF-β1. The chronic hepatitis B severe patients treated by enticavir is better.
引文
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6. Zoulim F.New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA.Hepatol,2005,42(3):302-308
7. Lai CL,Shouval D,Lok AS,et al.Entecavir versus lamivudine for patientswith HBeAg-negative chronic hepatitis B.N Engl J Med,2006,354(10):1011-1020
8.段忠辉,孟庆华.拉米夫定和阿德福韦及恩替卡韦治疗乙肝的现状和进展.中国全科医学,2007,10(1)：67-71
9. 耿长新,李金金,吕志国.恩替卡韦治疗慢性乙型肝炎30例.世界华人消化杂志,2009；26(4)：425-428
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17.病毒性肝炎防治方案(试行)[J].中华传染病杂志,1995,13(4)：241
18. 张红,李鑫,刘沛.恩替卡韦对慢性乙型肝炎抗病毒治疗的临床分析.药物与临床.2008,5(14)：64-65
19.高玉洁,杨志才,南春红,等.HBV-DNA与TGF-β1、TNF-α在慢性乙型肝炎中表达的影响.放射免疫学杂志,2004,17(1)：16-19
20. 梁艳丽,梅存金.恩替卡韦治疗慢性重型乙型肝炎疗效观察.淮海医药.2008,26(1)：46-47
21. Gao JC,Bao JF,Chen QW,et al.Level of serum and liver tissus TGF-betal in patients with live fiborsis due to chronic hepatitis.zhonghua Shi Yan He Lin chuang bing Du Xue Za Zhi,2008,22(5):354-357
22. Hu MG,Hu GF,Kim Y,et al.Role of p12(CDK2-AP1) in transfoming growth factor-beta1-mdeiatde growth suppression.Cancer Res,2004,15(2):490-499
23. 周明玉.TGF-β1刺激肝星状细胞的活化与肝纤维化的研究进展.贵州医药,2008,32(8)：751-753
24. Flisiak R,Pytel Korlczuk B,Prokopowicz D,et al.Circulating transfoming growth factor beta(1)as an indicator of heptaic function impaimrent in liver cirrhosis.Cytokine,2000,12(6):677-681
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2. 占国清,江山,郑三菊,等.干扰素治疗慢性乙型肝炎的临床疗效及其影响因素.医药导报,2007,26(12)：1429-1431
3. Honkoop P,Deman RA.Entecavir:a potent new antiviral drug for hepatitis.Expert Opin Investig Drugs,2003,12(4):683-688
4. Deman RA,Wolters LM,Nevens F,et al.Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection. Hepatology,2001, 34(3):578-582
5.马秀云, 蔡皓东,徐艳丽,等.恩替卡韦抗乙型肝炎病毒感染量效关系及安全性的研究.药物不良反应杂志,2007,4(9)：81-84
6. Zoulim F.New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA.Hepatol,2005,42(3):302-308
7. Lai CL,Shouval D,Lok AS,et al.Entecavir versus lamivudine for patientswith HBeAg-negative chronic hepatitis B.N Engl J Med,2006,354(10):1011-1020
8.段忠辉,孟庆华.拉米夫定和阿德福韦及恩替卡韦治疗乙肝的现状和进展.中国全科医学,2007,10(1)：67-71
9. 耿长新,李金金,吕志国.恩替卡韦治疗慢性乙型肝炎30例.世界华人消化杂志,2009；26(4)：425-428
10.张世益, 马晓兰,张玲,等.肝病患者血清TGF-β1水平及其临床意义.放射免疫学杂志,2006,19(2)：127-128
11. Flisiak R,Maxwell P,Prokopowicz D,et al.Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta 1-possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis. Hepatogastroenterology.2002,49(47):1369-72
12. Mauviel A.Transforming growth factor-beta:a key mediator of fibrosis. Methods Mol Med.2005,117(5):69-80
13.孙樱,宣世英,辛永宁,等.慢性乙型肝炎患者血清TGF-β1与肝组织纤维化及肝功能相关的研究.中华肝脏病杂志,2002,10(3)：62-63
14. Gressner AM,Chunfang G.A caseade-mechanism of fat storing cell activation forms the basis of the fibrogenic reaction of the liver,Verb Dtsch Ges Pathol,1995,79(6): 1-14
15.邱法忠,孙波.TGF-β1、MMP2检测在肝纤维化中的应用.放射免疫学杂志,2007,20(2)：123-124
16. Giannelli G, Bergamini C, Marinosci F, et al. Antifibrogenic effect of IFN-alpha2b on hepatic stellate cell activation by human hepatocytes.Interferon Cyt Res,2006;26(5):301-308
17.病毒性肝炎防治方案(试行)[J].中华传染病杂志,1995,13(4)：241
18. 张红,李鑫,刘沛.恩替卡韦对慢性乙型肝炎抗病毒治疗的临床分析.药物与临床.2008,5(14)：64-65
19.高玉洁,杨志才,南春红,等.HBV-DNA与TGF-β1、TNF-α在慢性乙型肝炎中表达的影响.放射免疫学杂志,2004,17(1)：16-19
20. 梁艳丽,梅存金.恩替卡韦治疗慢性重型乙型肝炎疗效观察.淮海医药.2008,26(1)：46-47
21. Gao JC,Bao JF,Chen QW,et al.Level of serum and liver tissus TGF-betal in patients with live fiborsis due to chronic hepatitis.zhonghua Shi Yan He Lin chuang bing Du Xue Za Zhi,2008,22(5):354-357
22. Hu MG,Hu GF,Kim Y,et al.Role of p12(CDK2-AP1) in transfoming growth factor-beta1-mdeiatde growth suppression.Cancer Res,2004,15(2):490-499
23. 周明玉.TGF-β1刺激肝星状细胞的活化与肝纤维化的研究进展.贵州医药,2008,32(8)：751-753
24. Flisiak R,Pytel Korlczuk B,Prokopowicz D,et al.Circulating transfoming growth factor beta(1)as an indicator of heptaic function impaimrent in liver cirrhosis.Cytokine,2000,12(6):677-681
25.刘芳,李兵顺,南月敏.慢性乙型肝炎患者血清转化生长因子β1在肝纤维化过程中的作用.中华肝脏病杂志,1999,17(4)：196-198
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