不同HBV DNA载量CHB患者肝功能酶学指标、T淋巴细胞亚群、细胞因子变化及相关性
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摘要
目的比较不同乙肝病毒DNA(HBV DNA)载量的慢性乙型肝炎(CHB)患者肝功能酶学指标、T淋巴细胞亚群、细胞因子水平变化,并分析各指标的相关性。方法 188例CHB患者按血清HBV-DNA载量分为阴性组35例、低拷贝组55例、中拷贝组56例、高拷贝组42例,另选20例同期健康体检者作为对照(对照组),采用全自动生化分析仪检测各组肝功能指标,流式细胞仪及相关抗体检测CD4~+T细胞、CD8~+T细胞亚群百分比,计算CD4~+T细胞/CD8~+T细胞值,ELISA法检测TNF、IFN-γ。结果与对照组和阴性组比较,低拷贝组、中拷贝组、高拷贝组ALT和AST水平升高(P均<0.05);与对照组比较,阴性组AST水平降低(P <0.05)。与对照组和阴性组比较,低拷贝组、中拷贝组、高拷贝组CD4~+T细胞、CD8~+T细胞比例及CD4~+T/CD8~+T降低(P均<0.05);与对照组比较,阴性组CD4~+T细胞、CD8~+T细胞比例降低,CD4~+T/CD8~+T升高(P均<0.05)。与对照组和阴性组比较,低拷贝组、中拷贝组、高拷贝组TNF、IFN-γ水平升高(P均<0.05);与对照组比较,阴性组TNF水平降低、IFN-γ水平升高(P均<0.05)。CHB患者ALT、AST水平与IFN-γ、TNF水平呈正相关(r分别为0.805、0.836、0.883、0.913,P均<0.05),CD4~+T、CD8~+T与IFN-γ、TNF水平呈负相关(r分别为-0.797、-0.831、-0.834、-0.820,P均<0.05)。CHB患者HBV DNA载量与IFN-γ、TNF水平呈正相关(r分别为0.902、0.940,P均<0.05),HBV DNA载量与CD4~+T、CD8~+T、CD4~+T/CD8~+T呈负相关(r分别为-0.820、-0.773、-0.930,P均<0.05)。结论随着HBV DNA载量增加,CHB患者CD4~+T、CD8~+T比例逐渐下降,ALT、AST及TNF、IFN-γ水平逐渐升高,HBV DNA载量在一程度上与CHB患者炎症细胞因子水平、肝功能受损程度具有一致性。
Objective To compare the changes in levels of hepatic enzymatic parameters,T lymphocyte subsets,and cytokines,and to analyze the correlation of these indexes in patients with chronic hepatitis B(CHB) with different HBV DNA loads.Methods Totally 188 CHB patients were divided into the negative group(n=35),low copy group(n=55),medium copy group(n=56),and high copy group(n=42) according to the loads of HBV-DNA in serum.Another 20 healthy people in the same period were selected as the control group.The liver function indexes of each group were detected by automatic biochemical analyzer.The percentage of CD4~+T cells and CD8~+T cells was detected by flow cytometry and its related antibodies.The CD4~+T/CD8~+T value was calculated.Tumor necrosis factor(TNF) and interferon-γ(IFN-γ)were detected by ELISA.Results Compared with the control group and the negative group,the levels of ALT and AST increased in the low copy group,the medium copy group,and the high copy group(both P<0.05).Compared with the control group,the level of AST in the negative group decreased(P<0.05).Compared with the control group and negative group,the levels of CD4~+T cells,CD8~+T cells,and CD4~+T/CD8~+T decreased in the low copy group,the medium copy group and the high copy group(all P<0.05).Compared with the control group,the levels of CD4~+T cells,CD8~+T cells decreased and CD4~+T/CD8~+T increased in the negative group(all P<0.05).Compared with the control group and the negative group,the level of TNF and IFN-γ increased in the low copy group,the medium copy group and the high copy group(all P<0.05).Compared with the control group,the levels of TNF decreased and IFN-γ increased in the negative group(both P<0.05).ALT and AST levels in the CHB patients were positively correlated with IFN-γ and TNF levels(r=0.805,0.836,0.883,and 0.913,respectively;all P<0.05),while CD4~+T cells and CD8~+T cells were negatively correlated with IFN-γ and TNF levels(r=-0.797,-0.831,-0.834,and-0.820,respectively;all P<0.05).HBV DNA load was positively correlated with IFN-γ and TNF levels in the CHB patients(r=0.902 and 0.940,both P<0.05),while HBV DNA load was negatively correlated with CD4~+T cells,CD8~+T cells and CD4~+T/CD8~+T(r=-0.820,-0.773,and-0.930,respectively,all P<0.05).Conclusions With the increase of HBV DNA load,the percentage of CD4~+T cells and CD8~+T cells in CHB patients gradually decreases,and the levels of ALT,AST,TNF,and IFN-γ gradually increase.To some extent,the DNA load of HBV is consistent with the inflammatory cytokine levels and degree of liver function damage in CHB patients.
Objective To compare the changes in levels of hepatic enzymatic parameters,T lymphocyte subsets,and cytokines,and to analyze the correlation of these indexes in patients with chronic hepatitis B(CHB) with different HBV DNA loads.Methods Totally 188 CHB patients were divided into the negative group(n=35),low copy group(n=55),medium copy group(n=56),and high copy group(n=42) according to the loads of HBV-DNA in serum.Another 20 healthy people in the same period were selected as the control group.The liver function indexes of each group were detected by automatic biochemical analyzer.The percentage of CD4~+T cells and CD8~+T cells was detected by flow cytometry and its related antibodies.The CD4~+T/CD8~+T value was calculated.Tumor necrosis factor(TNF) and interferon-γ(IFN-γ)were detected by ELISA.Results Compared with the control group and the negative group,the levels of ALT and AST increased in the low copy group,the medium copy group,and the high copy group(both P<0.05).Compared with the control group,the level of AST in the negative group decreased(P<0.05).Compared with the control group and negative group,the levels of CD4~+T cells,CD8~+T cells,and CD4~+T/CD8~+T decreased in the low copy group,the medium copy group and the high copy group(all P<0.05).Compared with the control group,the levels of CD4~+T cells,CD8~+T cells decreased and CD4~+T/CD8~+T increased in the negative group(all P<0.05).Compared with the control group and the negative group,the level of TNF and IFN-γ increased in the low copy group,the medium copy group and the high copy group(all P<0.05).Compared with the control group,the levels of TNF decreased and IFN-γ increased in the negative group(both P<0.05).ALT and AST levels in the CHB patients were positively correlated with IFN-γ and TNF levels(r=0.805,0.836,0.883,and 0.913,respectively;all P<0.05),while CD4~+T cells and CD8~+T cells were negatively correlated with IFN-γ and TNF levels(r=-0.797,-0.831,-0.834,and-0.820,respectively;all P<0.05).HBV DNA load was positively correlated with IFN-γ and TNF levels in the CHB patients(r=0.902 and 0.940,both P<0.05),while HBV DNA load was negatively correlated with CD4~+T cells,CD8~+T cells and CD4~+T/CD8~+T(r=-0.820,-0.773,and-0.930,respectively,all P<0.05).Conclusions With the increase of HBV DNA load,the percentage of CD4~+T cells and CD8~+T cells in CHB patients gradually decreases,and the levels of ALT,AST,TNF,and IFN-γ gradually increase.To some extent,the DNA load of HBV is consistent with the inflammatory cytokine levels and degree of liver function damage in CHB patients.
引文
[1]江若霞,赵丽敏,姚宏建,等.乙型病毒性肝炎患者T淋巴细胞亚群及免疫因子变化研究[J].中华医院感染学杂志,2016,26(13):2884-2887.
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[3]Gong Y,Zhan T,Li Q,et al.Serum progranulin levels are elevated in patients withchronic chepatitis B virus infection,reflecting viral load[J].Cytokine,2016,85(4):26-29.
[4]鲁晓娟,寇应琳,陈妍,等.HBV感染患者病毒载量对外周血T淋巴细胞、细胞因子及肝功能的影响[J].中华医院感染学杂志,2017,27(1):63-66.
[5]姚玮,王贵峰.CHB患者HBV DNA含量与T淋巴细胞亚群变化的分析[J].检验医学与临床,2014,11(21):3043-3046.
[6]中华医学会肝病学分会,中华医学会感染病学分会.CHB防治指南(2015年版)[J].实用肝脏病杂志,2016,19(3):389.
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[9]杨晨辰,黄睿,刘勇,等.慢性HBV感染者不同免疫状态下及抗病毒治疗后外周血T细胞亚群比例和细胞因子水平特点[J].中华实验和临床感染病杂志(电子版),2014,8(2):35-38.
[10]He D,Li M,Guo S,et al.Expression pattern of serum cytokines in hepatitis B virus infected patients with persistently normal alanine aminotransferase levels[J].J Clin Immunol,2013,33(7):1240-1249.
[11]李铃,敬雪明,朱其荣,等.乙肝病毒感染后不同临床类型及HBV DNA载量与外周血T细胞亚群变化的相关性分析[J].中国现代医学杂志,2015,25(17):35-39.
[12]Xu HZ,Liu YP,Guleng B,et al.Hepatitis B virus related hepatocelluar cinoma:pathogenic mechanisms and novel therapeutic interentions[J].Gastrointes Tumors,2014,1(3):135-145.
[13]Wang J,Zhu R,Gao B,et al.The enhanced immune responsse of hepatitis B virus DNA vaccine using Sio2 LDH nanoparticles as an adjuvant[J].Biomaterials,2014,35(1):466-478.
[14]王驭风,钱卫,夏澍.HBV不同感染状态者血清IL-21、IFN-γ水平变化及其临床意义[J].山东医药,2017,57(4):71-75.
[15]何亚,唐曙明,李爱敏,等.不同HBV DNA载量患者T细胞亚群及红细胞免疫指标的表达比较[J].中国医学创新,2018,15(1):37-40.
[16]马鹏.T细胞亚群及炎性因子对乙型病毒肝炎的诊断价值及相关性分析[J].现代仪器与医疗,2015,21(5):34-36.
[17]李彩东,杨勇卫,李惠军,等.乙型肝炎病毒携带者外周血IFN-γ、IL-32和IL-6的变化及临床相关性[J].国际检验医学杂志,2015,36(18):2622-2624.
[18]Yu S,Jia L,Zhang Y,et al.IL-12 induced the generation of IL-21 and IFN-γ-co-expressing poly-functional CD4+T cells from human naive CD4+T cells[J].Cell Cycle,2015,14(21):3362-3372.
[19]李曼,孙学华,周振华,等.CHB病毒感染者外周血T细胞γ干扰素和白细胞介素-4的水平变化[J].细胞与分子免疫学杂志,2016,32(2):240-244.
[20]Miyauchi T,Kanda T,Shinozaki M,et al.Efficacy of lamivudine or entacavir against virological rebound after achieving HBV DNAnegativity in chronic heptitis B petients[J].Int J Med Sci,2013,10(6):647-652.
[2]王海滨,张冬青,陈嫚,等.乙型病毒性肝炎患者HBV-DNA与乙肝标志物和肝功能指标关系的分析[J].感染、炎症、修复,2015,16(3):173-176.
[3]Gong Y,Zhan T,Li Q,et al.Serum progranulin levels are elevated in patients withchronic chepatitis B virus infection,reflecting viral load[J].Cytokine,2016,85(4):26-29.
[4]鲁晓娟,寇应琳,陈妍,等.HBV感染患者病毒载量对外周血T淋巴细胞、细胞因子及肝功能的影响[J].中华医院感染学杂志,2017,27(1):63-66.
[5]姚玮,王贵峰.CHB患者HBV DNA含量与T淋巴细胞亚群变化的分析[J].检验医学与临床,2014,11(21):3043-3046.
[6]中华医学会肝病学分会,中华医学会感染病学分会.CHB防治指南(2015年版)[J].实用肝脏病杂志,2016,19(3):389.
[7]王慰,任桂芳,刘玉珍,等.慢性乙型肝炎患者外周血T淋巴细胞亚群的变化[J].实用肝脏病杂志,2012,15(4):346-348.
[8]Saxena R,Kaur J.Th1/Th2 cytokines and their genotypes predictors of hepatitis B virus related hepatocellular carcinoma[J].World J Hepatol,2015,7(11):1571-1580.
[9]杨晨辰,黄睿,刘勇,等.慢性HBV感染者不同免疫状态下及抗病毒治疗后外周血T细胞亚群比例和细胞因子水平特点[J].中华实验和临床感染病杂志(电子版),2014,8(2):35-38.
[10]He D,Li M,Guo S,et al.Expression pattern of serum cytokines in hepatitis B virus infected patients with persistently normal alanine aminotransferase levels[J].J Clin Immunol,2013,33(7):1240-1249.
[11]李铃,敬雪明,朱其荣,等.乙肝病毒感染后不同临床类型及HBV DNA载量与外周血T细胞亚群变化的相关性分析[J].中国现代医学杂志,2015,25(17):35-39.
[12]Xu HZ,Liu YP,Guleng B,et al.Hepatitis B virus related hepatocelluar cinoma:pathogenic mechanisms and novel therapeutic interentions[J].Gastrointes Tumors,2014,1(3):135-145.
[13]Wang J,Zhu R,Gao B,et al.The enhanced immune responsse of hepatitis B virus DNA vaccine using Sio2 LDH nanoparticles as an adjuvant[J].Biomaterials,2014,35(1):466-478.
[14]王驭风,钱卫,夏澍.HBV不同感染状态者血清IL-21、IFN-γ水平变化及其临床意义[J].山东医药,2017,57(4):71-75.
[15]何亚,唐曙明,李爱敏,等.不同HBV DNA载量患者T细胞亚群及红细胞免疫指标的表达比较[J].中国医学创新,2018,15(1):37-40.
[16]马鹏.T细胞亚群及炎性因子对乙型病毒肝炎的诊断价值及相关性分析[J].现代仪器与医疗,2015,21(5):34-36.
[17]李彩东,杨勇卫,李惠军,等.乙型肝炎病毒携带者外周血IFN-γ、IL-32和IL-6的变化及临床相关性[J].国际检验医学杂志,2015,36(18):2622-2624.
[18]Yu S,Jia L,Zhang Y,et al.IL-12 induced the generation of IL-21 and IFN-γ-co-expressing poly-functional CD4+T cells from human naive CD4+T cells[J].Cell Cycle,2015,14(21):3362-3372.
[19]李曼,孙学华,周振华,等.CHB病毒感染者外周血T细胞γ干扰素和白细胞介素-4的水平变化[J].细胞与分子免疫学杂志,2016,32(2):240-244.
[20]Miyauchi T,Kanda T,Shinozaki M,et al.Efficacy of lamivudine or entacavir against virological rebound after achieving HBV DNAnegativity in chronic heptitis B petients[J].Int J Med Sci,2013,10(6):647-652.