恩替卡韦对HBeAg阳性慢性乙型肝炎初治患者免疫功能的影响分析
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摘要
目的探讨恩替卡韦对乙肝表面抗原(HBeAg)阳性慢性乙型肝炎初治患者免疫功能的影响。方法研究时间为2014年9月到2018年1月,采用回顾性、总结研究方法,选择HBeAg阳性慢性乙型肝炎初治患者98例作为本次研究对象,根据治疗方法的不同分为观察组50例与对照组48例,对照组给予拉夫米定治疗,观察组给予恩替卡韦治疗,2组都治疗观察2个月,记录2组免疫功能变化情况。结果治疗后观察组的HBV-DNA和HbeAg阴转率分别为98.0%和94.0%,对照组为85.7%和72.9%,观察组显著高于对照组(P<0.05)。治疗后2组的ALT、AST与TBiL水平都低于治疗前(P<0.05),观察组也低于对照组(P<0.05)。2组治疗后CD~+_3、CD~+_4均较治疗前显著增加(P<0.05),观察组高于对照组(P<0.05),2组治疗后CD~+_8较治疗前均显著降低(P<0.05),观察组低于对照组(P<0.05)。2组治疗期间的不良反应主要为疲劳、乏力、胸闷、恶心呕吐等,观察组发生率显著低于对照组(P<0.05)。结论恩替卡韦对HBeAg阳性慢性乙型肝炎初治患者的应用能提高HBV-DNA和HbeAg阴转率,减少治疗不良反应的发生,改善患者的肝功能,其作用机制可能与调节机体免疫功能有关。
Objective To investigate the effect of entecavir on immune function of patients with surface antigen(HBeAg)-positive chronic hepatitis B.Methods The clinical data about 98 patients with surface antigen(HBeAg)-positive chronic hepatitis B who were treated in our hospital from September 2014 to January 2018 were retrospectively analyzed. According to different treatment methods, these patients were divided into observation group(n=50) and control group(n=48). The patients in control group were treated by lovastatin, while those in observation group were treated by entecavir,with a treatment course of 2 months for both groups,then the changes of immune function were observed and compared between the two groups. Results After treatment, the negative conversion rates of HBV-DNA and HbeAg in observation group were 98.0% and 94.0% respectively, which were significantly higher than those(85.7% and 72.9%) in control group(P<0.05). After treatment, the levels of ALT, AST and TBiL in the two groups were lower than those before treatment(P<0.05), which were lower in the observation group than in the control group(P<0.05). In addition, CD~+_3 and CD~+_4 were significantly increased, as compared with those before treatment(P<0.05), which in observation group were significantly higher than those in control group(P<0.05). After treatment, CD~+ _8 levels in both groups were significantly lower than those before treatment(P<0.05), which in observation group were significantly lower than those in control group(P<0.05).The adverse reactions in both groups included fatigue, weakness, chest tightness, nausea and vomiting. The incidence rate of adverse reactions in observation group was significantly lower than that in control group(P<0.05).Conclusion The application of entecavir in patients with HBeAg-positive chronic hepatitis B can improve the negative conversion rate of HBV-DNA and HBeAg, reduce the incidence of adverse drug reactions, and improve the liver function of patients. The mechanism may be related to the regulation of immune function.
Objective To investigate the effect of entecavir on immune function of patients with surface antigen(HBeAg)-positive chronic hepatitis B.Methods The clinical data about 98 patients with surface antigen(HBeAg)-positive chronic hepatitis B who were treated in our hospital from September 2014 to January 2018 were retrospectively analyzed. According to different treatment methods, these patients were divided into observation group(n=50) and control group(n=48). The patients in control group were treated by lovastatin, while those in observation group were treated by entecavir,with a treatment course of 2 months for both groups,then the changes of immune function were observed and compared between the two groups. Results After treatment, the negative conversion rates of HBV-DNA and HbeAg in observation group were 98.0% and 94.0% respectively, which were significantly higher than those(85.7% and 72.9%) in control group(P<0.05). After treatment, the levels of ALT, AST and TBiL in the two groups were lower than those before treatment(P<0.05), which were lower in the observation group than in the control group(P<0.05). In addition, CD~+_3 and CD~+_4 were significantly increased, as compared with those before treatment(P<0.05), which in observation group were significantly higher than those in control group(P<0.05). After treatment, CD~+ _8 levels in both groups were significantly lower than those before treatment(P<0.05), which in observation group were significantly lower than those in control group(P<0.05).The adverse reactions in both groups included fatigue, weakness, chest tightness, nausea and vomiting. The incidence rate of adverse reactions in observation group was significantly lower than that in control group(P<0.05).Conclusion The application of entecavir in patients with HBeAg-positive chronic hepatitis B can improve the negative conversion rate of HBV-DNA and HBeAg, reduce the incidence of adverse drug reactions, and improve the liver function of patients. The mechanism may be related to the regulation of immune function.
引文
1 Tsai MC,Chen CH,Tseng PL,et al.Comparison of renal safety and efficacy of telbivudine,entecavir and tenofovir treatment in chronic hepatitis B patient:real world experience.Clin Microbiol Infect,2015,22:567-571.
2 Nafady-Hego H,Elgendy H,Nafady A,et al.Outcome of Hepatitis B Virus Infection After Living-Donor Liver Transplant:A Single-center Experience Over 20 Years.Exp Clin Transplant,2016,2:78-81.
3 Zhou P,Yang F,Wang J,et al.Improved Efficacy of a Pegylated Interferon-α-2a Stepwise Optimization Treatment Strategy in the Treatment of Hepatitis B e Antigen-positive Chronic Hepatitis B Patients.Medicine (Baltimore),2015,94:730-732.
4 王爱国,王运才,吴成勇.恩替卡韦对慢性乙型肝炎伴慢加急性肝衰竭病毒复制、肝功能及凝血功能的影响.中国药业,2018,27:35-37.
5 Xu Y,Wu XN,Shi YW,et al.Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 Month Virological Response to Entecavir Therapy:A Study of Strict Defined Hepatitis B virus Induced Cirrhosis.Chin Med J (Engl),2015,128:1867-1872.
6 Tawada A,Kanda T,Yokosuka O.Current and future directions for treating hepatitis B virus infection.World J Hepatol,2015,7:1541-1552.
7 Nsagha DS,Pokam BT,Assob JC,et al.HAART,DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon.BMC Public Health,2015,9:1040-1043.
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.肝脏,2018,23:88-90.
9 Papachrysos N,Hytiroglou P,Papalavrentios L,et al.Antiviral therapy leads to histological improvement of HBeAg-negative chronic hepatitis B patients.Ann Gastroenterol,2015,28:374-378.
10 Boettler T,Thimme R.Antiviral therapy in hepatitis B virus-associated liver cirrhosis.Dig Dis,2015,33:608-612.
11 叶长江.益气和血方联合恩替卡韦治疗乙肝肝硬化脾功能亢进的临床价值研究.实用临床医药杂志,2018,22:13-15,22.
12 De Nicolò A,Simiele M,Pensi D,et al.UPLC-MS/MS method for the simultaneous quantification of anti-HBV nucleos(t)ides analogs:Entecavir,lamivudine,telbivudine and tenofovir in plasma of HBV infected patients.J Pharm Biomed Anal,2015,22:127-132.
13 Liang X,Fan R,Sun J,et al.Effect of telbivudine versus other nucleos(t)ide analogs on HBeAg seroconversion and other outcomes in patients with chronic hepatitis B:a network meta-analysis.Adv Ther,2016,2:113-115.
14 朱琪,程变巧,林伟国,程英,黄少枫.慢性乙型肝炎HBVDNA载量与PD-1/PD-L1表达相关性研究.福建医药杂志,2018,40:8-10.
15 Wang Y,Liu S,Chen YU,et al.Evolution of entecavir-resistant hepatitis B virus during entecavir and adefovir dipivoxil combination therapy.Exp Ther Med,2016,11:117-123.
16 Sharifi Z.Natural history of chronic hepatitis B virus infection based on laboratory testing.Iran J Public Health,2014,43:990-993.
17 卢胜家,刘长灵,邵婷婷.恩替卡韦分散片治疗失代偿期乙肝肝硬化的临床疗效.中国生化药物杂志,2017,37:289-290.
18 Zeng Z,Han S,Hong W,et al.A tat-conjugated peptide nucleic acid tat-PNA-DR inhibits hepatitis B virus replication in vitro and in vivo by targeting LTR direct repeats of HBV RNA.Mol Ther Nucleic Acids,2016,15:295-300.
19 刁云辉,薛萌,樊宏伟,沙金平,孙长宇.胸腺肽α1注射剂联合恩替卡韦胶囊治疗肝硬化肝功能代偿期的临床研究.中国临床药理学杂志,2017,33:974-976.
20 Costenaro P,Penazzato M,Lundin R,et al.Predictors of treatment failure in HIV-Positive children receiving combination antiretroviral therapy:cohort data from mozambique and uganda.J Pediatric Infect Dis Soc,2015,4:39-48.
21 苏正昌.恩替卡韦联合水飞蓟宾治疗乙肝肝硬化效果观察及对肝纤维化和微炎症状态的影响.白求恩医学杂志,2018,16:21-23.
22 Despotovic A,Savic B,Salemovic D,et al.Isoniazid-resistant mycobact- erium kansasii in an HIV-positive patient,and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy:case report.Int J Infect Dis,2016,2:40-42.
23 Pandey G,Yadav SK,Mishra B.Preparation and characterization of isoniazid and lamivudine co-loaded polymeric microspheres.Artif Cells.Nanomed Biotechnol,2015,12:1-11.
24 郑崇广,汪世红,薛美华,等.恩替卡韦联合苦参素治疗慢乙肝纤维化的临床对照研究.北方药学,2018,15:57.
25 Mukonzo JK,Bisaso RK,Ogwal-Okeng J,et al.CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.Pharmacogenomics,2016,5:223-225.
2 Nafady-Hego H,Elgendy H,Nafady A,et al.Outcome of Hepatitis B Virus Infection After Living-Donor Liver Transplant:A Single-center Experience Over 20 Years.Exp Clin Transplant,2016,2:78-81.
3 Zhou P,Yang F,Wang J,et al.Improved Efficacy of a Pegylated Interferon-α-2a Stepwise Optimization Treatment Strategy in the Treatment of Hepatitis B e Antigen-positive Chronic Hepatitis B Patients.Medicine (Baltimore),2015,94:730-732.
4 王爱国,王运才,吴成勇.恩替卡韦对慢性乙型肝炎伴慢加急性肝衰竭病毒复制、肝功能及凝血功能的影响.中国药业,2018,27:35-37.
5 Xu Y,Wu XN,Shi YW,et al.Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 Month Virological Response to Entecavir Therapy:A Study of Strict Defined Hepatitis B virus Induced Cirrhosis.Chin Med J (Engl),2015,128:1867-1872.
6 Tawada A,Kanda T,Yokosuka O.Current and future directions for treating hepatitis B virus infection.World J Hepatol,2015,7:1541-1552.
7 Nsagha DS,Pokam BT,Assob JC,et al.HAART,DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon.BMC Public Health,2015,9:1040-1043.
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.肝脏,2018,23:88-90.
9 Papachrysos N,Hytiroglou P,Papalavrentios L,et al.Antiviral therapy leads to histological improvement of HBeAg-negative chronic hepatitis B patients.Ann Gastroenterol,2015,28:374-378.
10 Boettler T,Thimme R.Antiviral therapy in hepatitis B virus-associated liver cirrhosis.Dig Dis,2015,33:608-612.
11 叶长江.益气和血方联合恩替卡韦治疗乙肝肝硬化脾功能亢进的临床价值研究.实用临床医药杂志,2018,22:13-15,22.
12 De Nicolò A,Simiele M,Pensi D,et al.UPLC-MS/MS method for the simultaneous quantification of anti-HBV nucleos(t)ides analogs:Entecavir,lamivudine,telbivudine and tenofovir in plasma of HBV infected patients.J Pharm Biomed Anal,2015,22:127-132.
13 Liang X,Fan R,Sun J,et al.Effect of telbivudine versus other nucleos(t)ide analogs on HBeAg seroconversion and other outcomes in patients with chronic hepatitis B:a network meta-analysis.Adv Ther,2016,2:113-115.
14 朱琪,程变巧,林伟国,程英,黄少枫.慢性乙型肝炎HBVDNA载量与PD-1/PD-L1表达相关性研究.福建医药杂志,2018,40:8-10.
15 Wang Y,Liu S,Chen YU,et al.Evolution of entecavir-resistant hepatitis B virus during entecavir and adefovir dipivoxil combination therapy.Exp Ther Med,2016,11:117-123.
16 Sharifi Z.Natural history of chronic hepatitis B virus infection based on laboratory testing.Iran J Public Health,2014,43:990-993.
17 卢胜家,刘长灵,邵婷婷.恩替卡韦分散片治疗失代偿期乙肝肝硬化的临床疗效.中国生化药物杂志,2017,37:289-290.
18 Zeng Z,Han S,Hong W,et al.A tat-conjugated peptide nucleic acid tat-PNA-DR inhibits hepatitis B virus replication in vitro and in vivo by targeting LTR direct repeats of HBV RNA.Mol Ther Nucleic Acids,2016,15:295-300.
19 刁云辉,薛萌,樊宏伟,沙金平,孙长宇.胸腺肽α1注射剂联合恩替卡韦胶囊治疗肝硬化肝功能代偿期的临床研究.中国临床药理学杂志,2017,33:974-976.
20 Costenaro P,Penazzato M,Lundin R,et al.Predictors of treatment failure in HIV-Positive children receiving combination antiretroviral therapy:cohort data from mozambique and uganda.J Pediatric Infect Dis Soc,2015,4:39-48.
21 苏正昌.恩替卡韦联合水飞蓟宾治疗乙肝肝硬化效果观察及对肝纤维化和微炎症状态的影响.白求恩医学杂志,2018,16:21-23.
22 Despotovic A,Savic B,Salemovic D,et al.Isoniazid-resistant mycobact- erium kansasii in an HIV-positive patient,and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy:case report.Int J Infect Dis,2016,2:40-42.
23 Pandey G,Yadav SK,Mishra B.Preparation and characterization of isoniazid and lamivudine co-loaded polymeric microspheres.Artif Cells.Nanomed Biotechnol,2015,12:1-11.
24 郑崇广,汪世红,薛美华,等.恩替卡韦联合苦参素治疗慢乙肝纤维化的临床对照研究.北方药学,2018,15:57.
25 Mukonzo JK,Bisaso RK,Ogwal-Okeng J,et al.CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.Pharmacogenomics,2016,5:223-225.