替诺福韦酯和恩替卡韦治疗老年慢性乙型肝炎患者的抗病毒疗效及对致炎细胞因子的调节作用
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摘要
目的:比较替诺福韦酯(TDF)和恩替卡韦(ETV)治疗老年慢性乙型肝炎(CHB)患者的临床疗效及其对致炎细胞因子的调节作用,为其临床应用提供依据。方法:选取老年CHB患者93例,随机分为TDF组48例和ETV组45例,分别服用TDF (300mg/次,每天1次)和ETV (0.5mg/次,每天1次),连续观察48周。检测治疗前及治疗后4、12、24、36和48周时患者血清中HBV-DNA、丙氨酸氨基转移酶(ALT)、肿瘤坏死因子α(TNF-α)和白细胞介素10 (IL-10)水平,检验ALT复常率、HBV-DNA阴转率和HBeAg阴转率。结果:与治疗前比较,治疗后2组患者血清中HBV-DNA和ALT水平均明显降低(P<0.05),治疗4和12周时TDF组患者血清中HBV-DNA和ALT水平明显低于ETV组(P<0.05)。与治疗前比较,治疗后2组患者血清中TNF-α和IL-10水平均明显下降,治疗12周时开始2组患者血清TNF-α和IL-10水平差异均有统计学意义(P<0.05)。治疗后,2组患者ALT复常率逐渐升高,治疗4和12周时TDF组患者ALT复常率明显高于ETV组(P<0.05)。治疗4周时2组患者均出现完全病毒学应答,HBV-DNA阴转率逐渐升高,治疗4、12和24周时,TDF组患者HBV-DNA阴转率明显高于ETV组(P<0.05)。TDF组患者于12周开始出现HBeAg阴转,早于ETV组;ETV组患者于24周出现HBeAg阴转,2组患者HBeAg阴转率比较差异无统计学意义(P>0.05)。结论:TDF和ETV均可用于治疗老年CHB,TDF抗病毒作用起效早,肝功能恢复快,炎症反应轻,是临床治疗的理想抗病毒药物。
Objective:To compare the clinical efficacies of tenofovir(TDF)and entecavir(ETV)in the treatment of the aged patients with chronic hepatitis B(CHB)and their regulation on the inflammation factors,and to provide basis for their clinical application.Methods:A total of 93 aged patients with CHB were selected and randomly divided into TDF group(n=48)and ETV group(n=45).And the patients were treated with TDF(300 mg/time,1 time·d-1)and ETV(0.5 mg/time,1 time·d~(-1));the patients in two groups were observed for continuous 48 weeks.The levels of serum hepatitis B virus-deoxyribonucleic acid(HBV-DNA),glutamic pyruvic transaminase(ALT),and tumor necrosis factorα(TNF-α),interleukin-10(IL-10),the ALT recovery rates,the HBV-DNA negative conversion rates,and the HBeAg negative rates of the patients in two groups were detected before treatment and 4,12,24,36 and 48 weeks after treatment,respectively.Results:Compared with before treatment,the levels of serum HBV-DNA and ALT of the patients in two groups after treatment were decreased(P<0.05);the levels of serum HBV-DNA and ALT of the patients in TDF group were significantly lower than those in ETV at 4 and 12 weeks after treatment(P<0.05).Compared with before treatment,the levels of serum TNF-αand IL-10 of the patients in two groups after treatment were significantly decreased,and there were statistically significant differences between two groups at 12 weeks after treatment(P<0.05).After treatment,the ALT recovery rates of the patients in two groups were increased gradually;the ALT recovery rates in TDF group were significantly higher than those in ETV group(P<0.05)at 4 and 12 weeks after treatment.The patients in two groups showed complete virological responses at 4 weeks after treatment,and the HBV-DNA negative conversion rates were increased gradually.The negative conversion rates of HBV-DNA in TDF group were significantly higher than those in ETV group(P<0.05)at 4,12 and 24 weeks after treatment.The negative conversion of HBeAg in TDF group appeared at 12 weeks,which was earlier than that in ETV group;the negative conversion of HBeAg in ETV group appeared at 24 weeks;there was no significant difference in HBeAg negative conversion rate between two groups(P>0.05).Conclusion:Both TDF and ETV could be used to treat the aged patients with CHB.TDF has earlier antiviral effect and can bring quick recovery in liver function with lighter inflammatory reaction.TDF is an ideal antiviral drug for clinical treatment.
Objective:To compare the clinical efficacies of tenofovir(TDF)and entecavir(ETV)in the treatment of the aged patients with chronic hepatitis B(CHB)and their regulation on the inflammation factors,and to provide basis for their clinical application.Methods:A total of 93 aged patients with CHB were selected and randomly divided into TDF group(n=48)and ETV group(n=45).And the patients were treated with TDF(300 mg/time,1 time·d-1)and ETV(0.5 mg/time,1 time·d~(-1));the patients in two groups were observed for continuous 48 weeks.The levels of serum hepatitis B virus-deoxyribonucleic acid(HBV-DNA),glutamic pyruvic transaminase(ALT),and tumor necrosis factorα(TNF-α),interleukin-10(IL-10),the ALT recovery rates,the HBV-DNA negative conversion rates,and the HBeAg negative rates of the patients in two groups were detected before treatment and 4,12,24,36 and 48 weeks after treatment,respectively.Results:Compared with before treatment,the levels of serum HBV-DNA and ALT of the patients in two groups after treatment were decreased(P<0.05);the levels of serum HBV-DNA and ALT of the patients in TDF group were significantly lower than those in ETV at 4 and 12 weeks after treatment(P<0.05).Compared with before treatment,the levels of serum TNF-αand IL-10 of the patients in two groups after treatment were significantly decreased,and there were statistically significant differences between two groups at 12 weeks after treatment(P<0.05).After treatment,the ALT recovery rates of the patients in two groups were increased gradually;the ALT recovery rates in TDF group were significantly higher than those in ETV group(P<0.05)at 4 and 12 weeks after treatment.The patients in two groups showed complete virological responses at 4 weeks after treatment,and the HBV-DNA negative conversion rates were increased gradually.The negative conversion rates of HBV-DNA in TDF group were significantly higher than those in ETV group(P<0.05)at 4,12 and 24 weeks after treatment.The negative conversion of HBeAg in TDF group appeared at 12 weeks,which was earlier than that in ETV group;the negative conversion of HBeAg in ETV group appeared at 24 weeks;there was no significant difference in HBeAg negative conversion rate between two groups(P>0.05).Conclusion:Both TDF and ETV could be used to treat the aged patients with CHB.TDF has earlier antiviral effect and can bring quick recovery in liver function with lighter inflammatory reaction.TDF is an ideal antiviral drug for clinical treatment.
引文
[1]赵正斌,范文海.老年慢性乙型肝炎患者基因多态性与其耐药变异的相关性[J].中国老年学杂志,2017,37(2):417-419.
[2]KUO M T,TSENG P L,CHOU Y P,et al.Role of hepatitis B surface antigen in hepatitis B virus relapse after entecavir or tenofovir prophylaxis in patients undergoing cancer chemotherapy[J].J Gastroenterol Hepatol,2018,33(10):1766-1772.
[3]LIAW Y F,KAO J H,PIRATVISUTH T,et al.Erratum to:Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2012update[J].Hepatol Int,2012,6(4):809-810.
[4]HOU J,WANG G,WANG F,et al.Guideline of prevention and treatment for chronic hepatitis B(2015 Update)[J].J Clin Transl Hepatol,2017,5(4):297-318.
[5]KIM B C,JUNG S W,KIM E H,et al.Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine,adefovir,and entecavir[J].J Gastroenterol Hepatol,2015,30(10):1514-1521.
[6]谭俊,周密,胡皓钧,等.替诺福韦酯片对乙肝病毒感染经治患者补救治疗的疗效研究[J].中华医院感染学杂志,2017,27(21):4837-4841.
[7]邱英锋,王淑英.长期应用恩替卡韦治疗拉米夫定耐药的慢性乙型肝炎患者临床疗效及安全性分析[J].实用肝脏病杂志,2018,21(2):196-199.
[8]孔洪彬,宁振海,赵斗贵,等.恩替卡韦联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎患者疗效观察[J].肝脏,2018,23(1):88-90.
[9]李连海,齐敏.不同核苷类似物治疗乙型肝炎肝硬化失代偿期的疗效及对相关炎性细胞因子水平的影响[J].广西医科大学学报,2016,33(5):849-851.
[10]李秀梅,梁树人,李顺天,等.乙型肝炎患者外周血T细胞亚群的分析及意义[J].山东医药,2012,52(20):63-65.
[11]刘宁,徐杰,刘金花,等.慢性乙型肝炎、乙肝肝硬化、乙肝肝癌患者Th1/Th2型细胞因子水平变化研究[J].胃肠病学和肝病学杂志,2014,23(2):158-161.
[12]王贵强,王福生,成军,等.慢性乙型肝炎防治指南(2015年版)[J].实用肝脏病杂志,2016,19(03):389-400.
[13]VAN HEES S,BOURGEOIS S,VAN VLIERBERGHE H,et al.Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes[J].Aliment Pharmacol Ther,2018,47(8):1170-1180.
[14]YANG H C,SHIH Y F,LIU C J.Viral factors affecting the clinical outcomes of chronic hepatitis B[J].J Infect Dis,2017,216(suppl_8):S757-S764.
[15]王肖,王鹤,刘元元.替诺福韦酯与拉米夫定治疗老年慢性乙型肝炎的疗效比较[J].中国老年学杂志,2017,37(12):2978-2979.
[16]KESKIN O,ORMECI A C,BARAN B,et al.Efficacy of tenofovir in adefovir-experienced patients compared with treatment-naive patients with chronic hepatitis B[J].Antivir Ther(Lond),2014,19(6):543-550.
[17]POL S,LAMPERTICO P.First-line treatment of chronic hepatitis B with entecavir or tenofovir in‘real-life’settings:from clinical trials to clinical practice[J].J Viral Hepat,2012,19(6):377-386.
[18]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):165-167,208.
[19]汪梦.替诺福韦酯与拉米夫定治疗慢性乙肝疗效与安全性比较[J].当代医学,2018,24(7):107-109.
[20]丁荣蓉,施光峰,张占卿,等.替诺福韦酯和恩替卡韦对慢性乙型肝炎初治患者疗效的荟萃分析[J].肝脏,2017,22(5):400-403.
[21]YANG N,FENG J,ZHOU T,et al.Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients[J].J Med Virol,2018,90(7):1240-1245.
[22]WONG D,LITTLEJOHN M,EDWARDS R,et al.ALTflares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg-positive chronic hepatitis B[J].Liver Int,2018,38(10):1760-1769.
[23]胥松,顾行军,杨国旗,等.慢性乙肝与肝硬化患者血清IL-2、IL-6、IL-10、ChE和HA变化临床价值[J].国际检验医学杂志,2014,35(15):1986-1988.
[24]石庆凤,曾维群,陈敏,等.IL-10、TNF-α对慢性乙型肝炎患者树突状细胞的影响[J].免疫学杂志,2009,25(3):311-313,317.
[25]高沿航.恩替卡韦与替诺福韦治疗的慢性乙型肝炎患者发生肝细胞癌的风险:一项韩国全国性队列研究[J].临床肝胆病杂志,2018,34(12):2664.
[2]KUO M T,TSENG P L,CHOU Y P,et al.Role of hepatitis B surface antigen in hepatitis B virus relapse after entecavir or tenofovir prophylaxis in patients undergoing cancer chemotherapy[J].J Gastroenterol Hepatol,2018,33(10):1766-1772.
[3]LIAW Y F,KAO J H,PIRATVISUTH T,et al.Erratum to:Asian-Pacific consensus statement on the management of chronic hepatitis B:a 2012update[J].Hepatol Int,2012,6(4):809-810.
[4]HOU J,WANG G,WANG F,et al.Guideline of prevention and treatment for chronic hepatitis B(2015 Update)[J].J Clin Transl Hepatol,2017,5(4):297-318.
[5]KIM B C,JUNG S W,KIM E H,et al.Tenofovir-based rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine,adefovir,and entecavir[J].J Gastroenterol Hepatol,2015,30(10):1514-1521.
[6]谭俊,周密,胡皓钧,等.替诺福韦酯片对乙肝病毒感染经治患者补救治疗的疗效研究[J].中华医院感染学杂志,2017,27(21):4837-4841.
[7]邱英锋,王淑英.长期应用恩替卡韦治疗拉米夫定耐药的慢性乙型肝炎患者临床疗效及安全性分析[J].实用肝脏病杂志,2018,21(2):196-199.
[8]孔洪彬,宁振海,赵斗贵,等.恩替卡韦联合阿德福韦酯治疗拉米夫定耐药的慢性乙型肝炎患者疗效观察[J].肝脏,2018,23(1):88-90.
[9]李连海,齐敏.不同核苷类似物治疗乙型肝炎肝硬化失代偿期的疗效及对相关炎性细胞因子水平的影响[J].广西医科大学学报,2016,33(5):849-851.
[10]李秀梅,梁树人,李顺天,等.乙型肝炎患者外周血T细胞亚群的分析及意义[J].山东医药,2012,52(20):63-65.
[11]刘宁,徐杰,刘金花,等.慢性乙型肝炎、乙肝肝硬化、乙肝肝癌患者Th1/Th2型细胞因子水平变化研究[J].胃肠病学和肝病学杂志,2014,23(2):158-161.
[12]王贵强,王福生,成军,等.慢性乙型肝炎防治指南(2015年版)[J].实用肝脏病杂志,2016,19(03):389-400.
[13]VAN HEES S,BOURGEOIS S,VAN VLIERBERGHE H,et al.Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes[J].Aliment Pharmacol Ther,2018,47(8):1170-1180.
[14]YANG H C,SHIH Y F,LIU C J.Viral factors affecting the clinical outcomes of chronic hepatitis B[J].J Infect Dis,2017,216(suppl_8):S757-S764.
[15]王肖,王鹤,刘元元.替诺福韦酯与拉米夫定治疗老年慢性乙型肝炎的疗效比较[J].中国老年学杂志,2017,37(12):2978-2979.
[16]KESKIN O,ORMECI A C,BARAN B,et al.Efficacy of tenofovir in adefovir-experienced patients compared with treatment-naive patients with chronic hepatitis B[J].Antivir Ther(Lond),2014,19(6):543-550.
[17]POL S,LAMPERTICO P.First-line treatment of chronic hepatitis B with entecavir or tenofovir in‘real-life’settings:from clinical trials to clinical practice[J].J Viral Hepat,2012,19(6):377-386.
[18]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):165-167,208.
[19]汪梦.替诺福韦酯与拉米夫定治疗慢性乙肝疗效与安全性比较[J].当代医学,2018,24(7):107-109.
[20]丁荣蓉,施光峰,张占卿,等.替诺福韦酯和恩替卡韦对慢性乙型肝炎初治患者疗效的荟萃分析[J].肝脏,2017,22(5):400-403.
[21]YANG N,FENG J,ZHOU T,et al.Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients[J].J Med Virol,2018,90(7):1240-1245.
[22]WONG D,LITTLEJOHN M,EDWARDS R,et al.ALTflares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg-positive chronic hepatitis B[J].Liver Int,2018,38(10):1760-1769.
[23]胥松,顾行军,杨国旗,等.慢性乙肝与肝硬化患者血清IL-2、IL-6、IL-10、ChE和HA变化临床价值[J].国际检验医学杂志,2014,35(15):1986-1988.
[24]石庆凤,曾维群,陈敏,等.IL-10、TNF-α对慢性乙型肝炎患者树突状细胞的影响[J].免疫学杂志,2009,25(3):311-313,317.
[25]高沿航.恩替卡韦与替诺福韦治疗的慢性乙型肝炎患者发生肝细胞癌的风险:一项韩国全国性队列研究[J].临床肝胆病杂志,2018,34(12):2664.