替诺福韦联合干扰素α对慢性乙型肝炎患者肝功能及血清HBV-DNA转阴率的影响
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摘要
目的探讨替诺福韦联合干扰素α在慢性乙型肝炎患者中的应用效果。方法选取该院2015年5月至2017年4月收治的慢性乙型肝炎患者81例,按照随机数字表法分组,对照组40例采用恩替卡韦片治疗,观察组41例采用替诺福韦联合干扰素α治疗。比较两组临床治疗效果及治疗前后肝功能各指标[血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]、血清白细胞介素10(IL-10)、血清干扰素γ水平,并统计两组血清乙型肝炎病毒DNA(HBV-DNA)转阴率及不良反应发生情况。结果观察组治疗总有效率为90.24%(37/41),高于对照组的67.50%(27/40),差异有统计学意义(P<0.05);治疗48周后,观察组血清ALT、AST及TBIL水平低于对照组(P<0.05);治疗12周时,观察组血清干扰素γ水平明显升高且高于对照组,治疗48周后观察组血清IL-10、干扰素γ水平明显下降且低于对照组(P<0.05);观察组治疗12周时血清HBV-DNA转阴率为53.66%(22/41)、治疗24周时为63.41%(26/41)、治疗48周时为90.24%(37/41),高于对照组(30.00%、40.00%、70.00%),差异有统计学意义(P<0.05);观察组不良反应发生率为12.20%(5/41),对照组为12.50%(5/40),组间比较差异无统计学意义(P>0.05)。结论干扰素α联合替诺福韦可改善慢性乙型肝炎患者血清干扰素γ、IL-10水平,提高血清HBV-DNA转阴率,促进患者肝功能恢复,疗效确切,安全可靠。
Objective To explore the application effect of tenofovir combined with interferonαon liver function and serum HBV-DNA negative rate in patients with chronic hepatitis B.Methods A total of 81 patients with chronic hepatitis B treated in our hospital from May 2015 to April 2017 were divided into groups according to the random number table method.Forty cases in the control group were treated with entecavir tablets,and 41 cases in the observation group were treated with tenofovir combined with interferonα.The effects of clinical treatment,and the changes of liver function indexes [serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)]and serum interleukin-10(IL-10)and serum interferon gamma(IFN-γ)before and after treatment of the two groups were compared.The negative rate of hepatitis B virus-DNA(HBV-DNA)and the incidence of adverse reactions in two groups were also analyzed.Results The total effective rate of the observation group was 90.24%(37/41),higher than that of the control group[67.50%(27/40)],difference was statistically significant(P<0.05).After treatment for48 weeks,the serum levels of ALT,AST and TBIL in the observation group were significantly lower than those in the control group(P<0.05).At the 12 week of treatment,the level of serum IFN-γin the observation group was significantly higher than that of the control group(P<0.05).After 48 weeks of treatment,the level of serum IL-10 and IFN-γin the observation group decreased significantly and they were significantly lower than that of the control group(P<0.05).The negative rates of HBV-DNA in the observation group were 53.66%(22/41)at 12 weeks,63.41%(26/41)at 24 weeks and 90.24%(37/41)at 48 week of treatment,which were significantly higher than those of the control group(30.00%,40.00%,70.00%)(P<0.05).The incidence of adverse reactions in the observation group was 12.20%(5/41),that of control group was 12.50%(5/40).The difference had no statistical significance between the two groups(P>0.05).Conclusion The combination of interferonαand tenofovir can improve the level of serum IFN-γand IL-10 in patients with chronic hepatitis B,which could improve the negative rate of serum HBV-DNA and promote the recovery of liver function.The curative effect is accurate,safe and reliable.
Objective To explore the application effect of tenofovir combined with interferonαon liver function and serum HBV-DNA negative rate in patients with chronic hepatitis B.Methods A total of 81 patients with chronic hepatitis B treated in our hospital from May 2015 to April 2017 were divided into groups according to the random number table method.Forty cases in the control group were treated with entecavir tablets,and 41 cases in the observation group were treated with tenofovir combined with interferonα.The effects of clinical treatment,and the changes of liver function indexes [serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)]and serum interleukin-10(IL-10)and serum interferon gamma(IFN-γ)before and after treatment of the two groups were compared.The negative rate of hepatitis B virus-DNA(HBV-DNA)and the incidence of adverse reactions in two groups were also analyzed.Results The total effective rate of the observation group was 90.24%(37/41),higher than that of the control group[67.50%(27/40)],difference was statistically significant(P<0.05).After treatment for48 weeks,the serum levels of ALT,AST and TBIL in the observation group were significantly lower than those in the control group(P<0.05).At the 12 week of treatment,the level of serum IFN-γin the observation group was significantly higher than that of the control group(P<0.05).After 48 weeks of treatment,the level of serum IL-10 and IFN-γin the observation group decreased significantly and they were significantly lower than that of the control group(P<0.05).The negative rates of HBV-DNA in the observation group were 53.66%(22/41)at 12 weeks,63.41%(26/41)at 24 weeks and 90.24%(37/41)at 48 week of treatment,which were significantly higher than those of the control group(30.00%,40.00%,70.00%)(P<0.05).The incidence of adverse reactions in the observation group was 12.20%(5/41),that of control group was 12.50%(5/40).The difference had no statistical significance between the two groups(P>0.05).Conclusion The combination of interferonαand tenofovir can improve the level of serum IFN-γand IL-10 in patients with chronic hepatitis B,which could improve the negative rate of serum HBV-DNA and promote the recovery of liver function.The curative effect is accurate,safe and reliable.
引文
[1]LIM Y S,YOO B C,BYUN K S,et al.Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure:results of a randomised trial[J].Gut,2016,65(6):1042-1051.
[2]何佳,宁会彬,曾艳丽,等.血清中β2微球蛋白,视黄醇结合蛋白、胱抑素C在替诺福韦或恩替卡韦单药治疗慢性乙型肝炎早期肾功能变化中的意义[J].中华肝脏病杂志,2016,24(9):643-646.
[3]高峰,李建红,荀健,等.替诺福韦酯和阿德福韦酯治疗乙型肝炎e抗原阳性慢性乙型肝炎的疗效比较[J].中国药物与临床,2016,16(4):554-556.
[4]李忠斌,邵清,李梵,等.替诺福韦酯单独与联合恩替卡韦挽救治疗恩替卡韦治疗拉米夫定经治慢性乙型肝炎失败患者疗效比较[J].肝脏,2016,21(3):165-167.
[5]BROUWER W P,XIE Q,SONNEVELD M J,et al.Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B:a multicenter randomized trial(ares study)[J].Hepatology,2015,61(5):1512-1522.
[6]林厚雄.替诺福韦与恩替卡韦治疗HBeAg阳性初治慢性乙型肝炎患者的临床疗效[J].山东医药,2016,56(33):92-94.
[7]袁国盛,杨年欢,王欣欣,等.替诺福韦治疗其他核苷(酸)类药物耐药或应答不佳慢性乙型肝炎48周疗效分析[J].中华临床感染病杂志,2015,8(1):4-8.
[8]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].中华内科杂志,2011,50(2):168-179.
[9]陈俊,张玲玲,刘俊英.干扰素α-1b联合替比夫定序贯治疗慢性乙型肝炎的疗效及其对患者sPD-1和sICOS水平的影响[J].海南医学,2016,27(13):2104-2107.
[10]朱小荣,于锋,王坚.聚乙二醇干扰素α-2a与恩替卡韦辅治慢性乙型肝炎的临床疗效及安全性比较[J].临床合理用药杂志,2015,8(29):1-2.
[11]FONTAINE H,KAHI S,CHAZALLON C,et al.AntiHBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B:a randomised trial-ANRS HB02VAC-ADN[J].Gut,2015,64(1):139-147.
[12]朱丽,王丽,曾义岚,等.聚乙二醇干扰素α-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究[J].实用药物与临床,2016,19(1):110-113.
[13]郭斯敏,王晖,周惠娟,等.接受恩替卡韦治疗的e抗原阳性慢性乙型肝炎患者短程加用聚乙二醇干扰素-α-2a的抗病毒疗效和影响因素[J].中华传染病杂志,2015,33(1):14-19.
[14]徐建明,李兵,游红勇,等.恩替卡韦联合替诺福韦与恩替卡韦联合阿德福韦治疗拉米夫定耐药性慢性乙型肝炎患者疗效比较[J].检验医学与临床,2016,13(13):1788-1791.
[15]杨建锋.恩替卡韦联合干扰素治疗HBeAg阳性慢性乙型肝炎的临床效果[J].北方药学,2017,14(7):92-93.
[16]梁娴,荀运浩,王薇薇,等.HBeAg阳性慢性乙型肝炎患者中医体质与聚乙二醇干扰素α治疗应答的相关性[J].中西医结合肝病杂志,2016,26(2):72-73.
[17]施寒艳,徐晓蓉.α-干扰素联合恩替卡韦治疗慢性乙型肝炎患者疗效研究[J].实用肝脏病杂志,2017,17(4):488-489.
[18]阿力木江·毛拉艾沙,布力布力·马那甫,古丽加孜依拉,等.不同用药方案治疗HBeAg阳性慢性乙型肝炎的效果及对血清IFN-γ,IL-10的影响[J].中国医药导报,2017,14(5):137-140.
[19]李志强,何玉霞,耿建洪,等.聚乙二醇a干扰素对慢性乙型肝炎患者血清IFN-γ、IL-17、IL-10的影响作用及机制[J].世界华人消化杂志,2016,24(1):116-120.
[20]耿爱文,肖丽,咸建春,等.慢性乙型肝炎核苷酸类似物耐药患者外周血IL-21、γ-IFN、IL-10及β-TGF变化的临床研究[J].解放军医药杂志,2016,28(9):69-71.
[21]吴敏.慢性乙型肝炎患者病毒载量与IFN-γ、IL-10、CD19~(+)水平的相关性[J].肝脏,2015,20(4):320-323.
[22]骆佩怡,唐正运,刘伟东.替诺福韦酯单用治疗慢性乙型肝炎的临床疗效研究[J].中国全科医学,2015,18(34):4216-4219.
[2]何佳,宁会彬,曾艳丽,等.血清中β2微球蛋白,视黄醇结合蛋白、胱抑素C在替诺福韦或恩替卡韦单药治疗慢性乙型肝炎早期肾功能变化中的意义[J].中华肝脏病杂志,2016,24(9):643-646.
[3]高峰,李建红,荀健,等.替诺福韦酯和阿德福韦酯治疗乙型肝炎e抗原阳性慢性乙型肝炎的疗效比较[J].中国药物与临床,2016,16(4):554-556.
[4]李忠斌,邵清,李梵,等.替诺福韦酯单独与联合恩替卡韦挽救治疗恩替卡韦治疗拉米夫定经治慢性乙型肝炎失败患者疗效比较[J].肝脏,2016,21(3):165-167.
[5]BROUWER W P,XIE Q,SONNEVELD M J,et al.Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B:a multicenter randomized trial(ares study)[J].Hepatology,2015,61(5):1512-1522.
[6]林厚雄.替诺福韦与恩替卡韦治疗HBeAg阳性初治慢性乙型肝炎患者的临床疗效[J].山东医药,2016,56(33):92-94.
[7]袁国盛,杨年欢,王欣欣,等.替诺福韦治疗其他核苷(酸)类药物耐药或应答不佳慢性乙型肝炎48周疗效分析[J].中华临床感染病杂志,2015,8(1):4-8.
[8]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].中华内科杂志,2011,50(2):168-179.
[9]陈俊,张玲玲,刘俊英.干扰素α-1b联合替比夫定序贯治疗慢性乙型肝炎的疗效及其对患者sPD-1和sICOS水平的影响[J].海南医学,2016,27(13):2104-2107.
[10]朱小荣,于锋,王坚.聚乙二醇干扰素α-2a与恩替卡韦辅治慢性乙型肝炎的临床疗效及安全性比较[J].临床合理用药杂志,2015,8(29):1-2.
[11]FONTAINE H,KAHI S,CHAZALLON C,et al.AntiHBV DNA vaccination does not prevent relapse after discontinuation of analogues in the treatment of chronic hepatitis B:a randomised trial-ANRS HB02VAC-ADN[J].Gut,2015,64(1):139-147.
[12]朱丽,王丽,曾义岚,等.聚乙二醇干扰素α-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究[J].实用药物与临床,2016,19(1):110-113.
[13]郭斯敏,王晖,周惠娟,等.接受恩替卡韦治疗的e抗原阳性慢性乙型肝炎患者短程加用聚乙二醇干扰素-α-2a的抗病毒疗效和影响因素[J].中华传染病杂志,2015,33(1):14-19.
[14]徐建明,李兵,游红勇,等.恩替卡韦联合替诺福韦与恩替卡韦联合阿德福韦治疗拉米夫定耐药性慢性乙型肝炎患者疗效比较[J].检验医学与临床,2016,13(13):1788-1791.
[15]杨建锋.恩替卡韦联合干扰素治疗HBeAg阳性慢性乙型肝炎的临床效果[J].北方药学,2017,14(7):92-93.
[16]梁娴,荀运浩,王薇薇,等.HBeAg阳性慢性乙型肝炎患者中医体质与聚乙二醇干扰素α治疗应答的相关性[J].中西医结合肝病杂志,2016,26(2):72-73.
[17]施寒艳,徐晓蓉.α-干扰素联合恩替卡韦治疗慢性乙型肝炎患者疗效研究[J].实用肝脏病杂志,2017,17(4):488-489.
[18]阿力木江·毛拉艾沙,布力布力·马那甫,古丽加孜依拉,等.不同用药方案治疗HBeAg阳性慢性乙型肝炎的效果及对血清IFN-γ,IL-10的影响[J].中国医药导报,2017,14(5):137-140.
[19]李志强,何玉霞,耿建洪,等.聚乙二醇a干扰素对慢性乙型肝炎患者血清IFN-γ、IL-17、IL-10的影响作用及机制[J].世界华人消化杂志,2016,24(1):116-120.
[20]耿爱文,肖丽,咸建春,等.慢性乙型肝炎核苷酸类似物耐药患者外周血IL-21、γ-IFN、IL-10及β-TGF变化的临床研究[J].解放军医药杂志,2016,28(9):69-71.
[21]吴敏.慢性乙型肝炎患者病毒载量与IFN-γ、IL-10、CD19~(+)水平的相关性[J].肝脏,2015,20(4):320-323.
[22]骆佩怡,唐正运,刘伟东.替诺福韦酯单用治疗慢性乙型肝炎的临床疗效研究[J].中国全科医学,2015,18(34):4216-4219.