可溶性人类白细胞抗原G对丙型肝炎初治患者标准化治疗疗效的影响
|
摘要
目的:探讨可溶性人类白细胞抗原G(s HLA-G)对慢性丙型肝炎(CHC)患者聚乙二醇干扰素联合利巴韦林抗病毒治疗疗效的影响。方法:选择2013年10月至2015年10月就诊的63例CHC患者,分别采用基因芯片法、RT-PCR法和ELISA方法检测丙型肝炎病毒(HCV)基因型、HCV RNA和s HLA-G。所有患者接受聚乙二醇干扰素皮下注射,联合口服利巴韦林抗病毒治疗。分析获得持续病毒学应答(SVR)的影响因素。结果:SVR组女性和非基因1型比例均显著高于非持续病毒学应答(NSVR)组(女性:70.59%vs.44.83%,χ2=4.285;非基因1型:82.76%vs.55.88%,χ2=5.217,P均<0.05),其余基线指标均无统计学差异(P均>0.05)。NSVR组患者治疗前血浆s HLA-G水平显著高于SVR组[1.85(1.49-16.00)ng/L vs.1.53(1.36-2.80)ng/L;U=329.00,P<0.05]。经过多变量logistic回归分析,发现s HLA-G和HCV基因型是与治疗结局相关的独立影响因子,Exp(B)(95%CI)分别为0.922(0.868-0.978)、14.204(1.898-106.289)。结论:s HLA-G对丙型肝炎初治患者标准化治疗疗效有重要影响,特别是低水平者更容易获得持续病毒学应答。
AIM:To investigate the effect of soluble human leukocyte antigen G(s HLA-G) on the efficacy of pegylated interferon combined with ribavirin in the treatment of chronic hepatitis C(CHC).METHODS:A total of 63 CHC patients from October 2013 to October 2015 were enrolled.The genotype of hepatitis C virus(HCV),HCV RNA and s HLA-G were detected by gene chip,RTPCR and ELISA method accordingly.All patients received a subcutaneous injection of pegylated interferon combined with oral ribavirin.The factors affecting the sustained virological response(SVR)were observed and analyzed.RESULTS:The proportion of female and non-genotype 1 in SVR group was significantly higher than that in non-sustained virological response(NSVR) group(female:70.59% vs.44.83%,χ2= 4.285;non-genotype 1:82.76% vs.55.88%,χ2= 5.217,P < 0.05);other baseline indexes presented no significant difference(P > 0.05).The level of plasma s HLA-G before treatment in NSVR group was significantly higher than that in SVR group[1.85(1.49-16.00) ng/L vs.1.53(1.36-2.80) ng/L;U = 329.00,P <0.05].After multivariable logistic regression analysis,s HLA-G and HCV genotypes were the independent influencing factors associated with the outcome of treatment with Exp(B)(95% CI) were0.922(0.868-0.978) and 14.204(1.898-106.289),respectively.CONCLUSION:s HLA-G exhibits an important effect on the standardized treatment of hepatitis C patients,and patients with low s HLA-G level are more likely to achieve a sustained virological response.
AIM:To investigate the effect of soluble human leukocyte antigen G(s HLA-G) on the efficacy of pegylated interferon combined with ribavirin in the treatment of chronic hepatitis C(CHC).METHODS:A total of 63 CHC patients from October 2013 to October 2015 were enrolled.The genotype of hepatitis C virus(HCV),HCV RNA and s HLA-G were detected by gene chip,RTPCR and ELISA method accordingly.All patients received a subcutaneous injection of pegylated interferon combined with oral ribavirin.The factors affecting the sustained virological response(SVR)were observed and analyzed.RESULTS:The proportion of female and non-genotype 1 in SVR group was significantly higher than that in non-sustained virological response(NSVR) group(female:70.59% vs.44.83%,χ2= 4.285;non-genotype 1:82.76% vs.55.88%,χ2= 5.217,P < 0.05);other baseline indexes presented no significant difference(P > 0.05).The level of plasma s HLA-G before treatment in NSVR group was significantly higher than that in SVR group[1.85(1.49-16.00) ng/L vs.1.53(1.36-2.80) ng/L;U = 329.00,P <0.05].After multivariable logistic regression analysis,s HLA-G and HCV genotypes were the independent influencing factors associated with the outcome of treatment with Exp(B)(95% CI) were0.922(0.868-0.978) and 14.204(1.898-106.289),respectively.CONCLUSION:s HLA-G exhibits an important effect on the standardized treatment of hepatitis C patients,and patients with low s HLA-G level are more likely to achieve a sustained virological response.
引文
[1]Mohd Hanafiah K,Groeger J,Flaxman AD,et al.Global epidemiology of hepatitis C virus infection:new estimates of age-specific antibody to HCV seroprevalence[J].Hepatology,2013,57:1333-1342.
[2]Irshad M,Mankotia DS,Irshad K.An insight into the diagnosis and pathogenesis of hepatitis C virus infection[J].World J Gastroenterol,2013,19:7896-7909.
[3]中华医学会肝病学分会,中华医学会感染病学分会.丙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1961-1979.
[4]丁世雄,周文红,胡爱荣,等.宁波地区丙型肝炎病毒基因分型检测[J].中国卫生检验杂志,2011,21(10):2453-2454.
[5]Hezode C,Forestier N,Dusheiko G,et al.Telaprevir and peginterferon with or without ribavirin for chronic HCV infection[J].N Engl J Med,2009,360:1839-1850.
[6]游春芳,周利民,邓薇.基因1b型慢性丙型肝炎患者血清铁蛋白水平与聚乙二醇干扰素抗病毒疗效的关系[J].临床肝胆病杂志,2017,33(9):1713-1716.
[7]Kwon JH,Bae SH.Current status and clinical course of hepatitis C virus in Korea[J].Korean J Gastroenterol,2008,51:360-367.
[8]李小宁,杨正海,李静.不同基因型丙型肝炎病毒非结构蛋白NS3对端粒酶活性的研究[J].中国临床药理学与治疗学,2015,20(2):128-131.
[9]徐严,斯庆图娜拉,郎轶宣,等.聚乙二醇干扰素α-2a个体化抗病毒治疗慢性丙型肝炎的疗效[J].中华传染病杂志,2012,30(3):165-169.
[10]刘娜,徐光华,李春霞,等.影响丙型肝炎抗病毒疗效因素的研究进展[J].医学综述,2015,8(17):3082-3084.
[11]崔燕平,管珊,王金燕,等.聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效分析[J].国际流行病学传染病学杂志,2016,43(5):348-350.
[12]贾因棠,段晓红,杨中鑫,等.IL-28B、IFNL4基因多态性与慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林抗病毒疗效相关性的研究[J].中华肝脏病杂志,2017,25(7):529-532.
[13]陈新月,尚佳,杨瑞锋,等.难治性慢性丙型肝炎初治患者优化治疗后的病毒学应答率研究[J].中华肝脏病杂志,2015,23(6):412-417.
[14]周明琴,蒋素文,胡爱荣,等.慢性丙型肝炎患者标准化治疗应答的相关因素分析[J].中华全科医学,2016,14(2):240-242.
[15]窦晓光.影响丙型肝炎初治患者标准化治疗疗效的相关因素及对策[J].中华肝脏病杂志,2013,21(6):406-407.
[16]Dai CY,Chuang WL,Hsieh MY,et al.Human leukocyte antigen alleles and the response to PEGylated interferon/ribavirin therapy in chronic hepatitis C patients[J].Antiviral Res,2010,85(2):396-402.
[17]Fitzmaurice K,Hurst J,Dring M,et al.Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection[J].Gut,2015,64(5):813-819.
[18]胡彬,颜卫华.人类白细胞抗原-G与肝脏疾病研究进展[J].中华传染病杂志,2017,35(3):187-189.
[19]de Oliveira Crispim JC,Silva TG,Souto FJ,et al.Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection[J].Hum Immunol,2012,73(3):258-262.
[20]Amiot L,Vu N,Rauch M,et al.Expression of HLAG by mast cells is associated with hepatitis C virus-induced liver fibrosis[J].J Hepatol,2014,60(2):245-252.
[21]Weng PJ,Fu YM,Ding SX,et al.Elevation of plasma soluble human leukocyte antigen-G in patients with chronic hepatitis C virus infection[J].Hum Immunol,2011,72:406-411.
[2]Irshad M,Mankotia DS,Irshad K.An insight into the diagnosis and pathogenesis of hepatitis C virus infection[J].World J Gastroenterol,2013,19:7896-7909.
[3]中华医学会肝病学分会,中华医学会感染病学分会.丙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1961-1979.
[4]丁世雄,周文红,胡爱荣,等.宁波地区丙型肝炎病毒基因分型检测[J].中国卫生检验杂志,2011,21(10):2453-2454.
[5]Hezode C,Forestier N,Dusheiko G,et al.Telaprevir and peginterferon with or without ribavirin for chronic HCV infection[J].N Engl J Med,2009,360:1839-1850.
[6]游春芳,周利民,邓薇.基因1b型慢性丙型肝炎患者血清铁蛋白水平与聚乙二醇干扰素抗病毒疗效的关系[J].临床肝胆病杂志,2017,33(9):1713-1716.
[7]Kwon JH,Bae SH.Current status and clinical course of hepatitis C virus in Korea[J].Korean J Gastroenterol,2008,51:360-367.
[8]李小宁,杨正海,李静.不同基因型丙型肝炎病毒非结构蛋白NS3对端粒酶活性的研究[J].中国临床药理学与治疗学,2015,20(2):128-131.
[9]徐严,斯庆图娜拉,郎轶宣,等.聚乙二醇干扰素α-2a个体化抗病毒治疗慢性丙型肝炎的疗效[J].中华传染病杂志,2012,30(3):165-169.
[10]刘娜,徐光华,李春霞,等.影响丙型肝炎抗病毒疗效因素的研究进展[J].医学综述,2015,8(17):3082-3084.
[11]崔燕平,管珊,王金燕,等.聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效分析[J].国际流行病学传染病学杂志,2016,43(5):348-350.
[12]贾因棠,段晓红,杨中鑫,等.IL-28B、IFNL4基因多态性与慢性丙型肝炎患者聚乙二醇干扰素联合利巴韦林抗病毒疗效相关性的研究[J].中华肝脏病杂志,2017,25(7):529-532.
[13]陈新月,尚佳,杨瑞锋,等.难治性慢性丙型肝炎初治患者优化治疗后的病毒学应答率研究[J].中华肝脏病杂志,2015,23(6):412-417.
[14]周明琴,蒋素文,胡爱荣,等.慢性丙型肝炎患者标准化治疗应答的相关因素分析[J].中华全科医学,2016,14(2):240-242.
[15]窦晓光.影响丙型肝炎初治患者标准化治疗疗效的相关因素及对策[J].中华肝脏病杂志,2013,21(6):406-407.
[16]Dai CY,Chuang WL,Hsieh MY,et al.Human leukocyte antigen alleles and the response to PEGylated interferon/ribavirin therapy in chronic hepatitis C patients[J].Antiviral Res,2010,85(2):396-402.
[17]Fitzmaurice K,Hurst J,Dring M,et al.Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection[J].Gut,2015,64(5):813-819.
[18]胡彬,颜卫华.人类白细胞抗原-G与肝脏疾病研究进展[J].中华传染病杂志,2017,35(3):187-189.
[19]de Oliveira Crispim JC,Silva TG,Souto FJ,et al.Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection[J].Hum Immunol,2012,73(3):258-262.
[20]Amiot L,Vu N,Rauch M,et al.Expression of HLAG by mast cells is associated with hepatitis C virus-induced liver fibrosis[J].J Hepatol,2014,60(2):245-252.
[21]Weng PJ,Fu YM,Ding SX,et al.Elevation of plasma soluble human leukocyte antigen-G in patients with chronic hepatitis C virus infection[J].Hum Immunol,2011,72:406-411.