苦参碱注射液联合替诺福韦酯治疗拉米夫定耐药慢性乙型肝炎的临床研究
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摘要
目的探讨苦参碱注射液联合富马酸替诺福韦二吡呋酯片治疗拉米夫定耐药慢性乙型肝炎的临床疗效。方法选取2014年2月—2016年10月赤峰市传染病防治医院收治的拉米夫定耐药的慢性乙型肝炎患者92例为研究对象,按随机数字表法将患者分为对照组和治疗组,每组各46例。对照组口服富马酸替诺福韦二吡呋酯片,300 mg/次,1次/d。治疗组在对照组基础上静脉滴注苦参碱注射液,150 mg加入到5%葡萄糖溶液250 m L中,1次/d,连续给药2周后休息2周。两组均治疗48周。观察两组的临床疗效,比较两组的血清学指标、病毒学指标、肝功能指标、肝纤维化指标。结果治疗后,对照组和治疗组的总有效率分别为76.09%、91.30%,两组比较差异有统计学意义(P<0.05)。治疗24、48周后,两组乙肝病毒的脱氧核糖核酸(HBV-DNA)阴转率、乙型肝炎E抗原(HBe Ag)阴转率、HBe Ag血清转换率均明显升高,与同组治疗12周后比较差异有统计学意义(P<0.05);且治疗组这些观察指标明显高于同期对照组,两组比较差异具有统计学意义(P<0.05)。治疗24、48周后,两组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、总胆红素(TBIL)水平均明显下降,同组治疗前后比较差异有统计学意义(P<0.05);且治疗组这些观察指标明显低于同期对照组,两组比较差异具有统计学意义(P<0.05)。治疗24、48周后,两组血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)水平均明显下降,同组治疗前后比较差异有统计学意义(P<0.05);且治疗组这些观察指标明显低于同期对照组,两组比较差异具有统计学意义(P<0.05)。结论苦参碱注射液联合富马酸替诺福韦二吡呋酯片治疗拉米夫定耐药慢性乙型肝炎具有较好的临床疗效,能提高HBV-DNA阴转率、HBe Ag阴转率和HBe Ag血清转换率,改善肝功能和肝纤维化,具有一定临床推广应用价值。
Objective To investigate the clinical efficacy of Matrine Injection combined with Tenofovir Disoproxil Fumarate Tablets in treatment of lamivudine-resistant chronic hepatitis B. Methods Patients(92 cases) with lamivudine-resistant chronic hepatitis B in Chifeng Infectious Disease Prevention and Control Hospital from February 2014 to October 2016 were randomly divided into control and treatment groups, and each group had 46 cases. Patients in the control group were po administered with Tenofovir Disoproxil Fumarate Tablets, 300 mg/time, once daily. Patients in the treatment group were iv administered with Matrine Injection on the basis of the control group, 150 mg added into 5% glucose solution 250 m L, once daily. After 2 weeks of continuous administration, they rested for 2 weeks. Patients in two groups were treated for 48 weeks. After treatment, the clinical efficacies were evaluated, and serological and virological index, liver function index, liver fibrosis index in two groups were compared. Results After treatment, the clinical efficacies in the control and treatment groups were 76.09% and 91.30%, respectively, and there was difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, HBV-DNA negative conversion rate, HBe Ag negative conversion rate, and HBe Ag seroconversion rate in two groups were significantly increased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly higher than those at the same period in the control group, with significant difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, the levels of ALT, AST and TBIL in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly lower than those at the same period in the control group, with significant difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, the levels of HA, LN, PCⅢ, and Ⅳ-C in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly lower than those at the same time in the control group, with significant difference between two groups(P < 0.05). Conclusion Matrine Injection combined with Tenofovir Disoproxil Fumarate Tablets has clinical curative effect in treatment of lamivudine-resistant chronic hepatitis B, can increase HBV-DNA negative conversion rate, HBe Ag negative conversion rate, and HBe Ag seroconversion rate, improve liver function and liver fibrosis, which has a certain clinical application value.
Objective To investigate the clinical efficacy of Matrine Injection combined with Tenofovir Disoproxil Fumarate Tablets in treatment of lamivudine-resistant chronic hepatitis B. Methods Patients(92 cases) with lamivudine-resistant chronic hepatitis B in Chifeng Infectious Disease Prevention and Control Hospital from February 2014 to October 2016 were randomly divided into control and treatment groups, and each group had 46 cases. Patients in the control group were po administered with Tenofovir Disoproxil Fumarate Tablets, 300 mg/time, once daily. Patients in the treatment group were iv administered with Matrine Injection on the basis of the control group, 150 mg added into 5% glucose solution 250 m L, once daily. After 2 weeks of continuous administration, they rested for 2 weeks. Patients in two groups were treated for 48 weeks. After treatment, the clinical efficacies were evaluated, and serological and virological index, liver function index, liver fibrosis index in two groups were compared. Results After treatment, the clinical efficacies in the control and treatment groups were 76.09% and 91.30%, respectively, and there was difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, HBV-DNA negative conversion rate, HBe Ag negative conversion rate, and HBe Ag seroconversion rate in two groups were significantly increased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly higher than those at the same period in the control group, with significant difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, the levels of ALT, AST and TBIL in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly lower than those at the same period in the control group, with significant difference between two groups(P < 0.05). After treatment for 24 and 48 weeks, the levels of HA, LN, PCⅢ, and Ⅳ-C in two groups were significantly decreased, and the difference was statistically significant in the same group(P < 0.05). And the observational indexes in the treatment group were significantly lower than those at the same time in the control group, with significant difference between two groups(P < 0.05). Conclusion Matrine Injection combined with Tenofovir Disoproxil Fumarate Tablets has clinical curative effect in treatment of lamivudine-resistant chronic hepatitis B, can increase HBV-DNA negative conversion rate, HBe Ag negative conversion rate, and HBe Ag seroconversion rate, improve liver function and liver fibrosis, which has a certain clinical application value.
引文
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[5]Wang X,Lin H,Zhang R.The clinical efficacy and adverse effects of interferon combined with matrine in chronic hepatitis B:a systematic review and metaanalysis[J].Phytother Res,2017,31(6):849-857.
[6]中华医学会肝病学分会.慢性乙型肝炎诊断标准(2015年版)[J].中西医结合肝病杂志,2015,25(6):384.
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[8]欧阳雅博,李庆,魏飞力,等.慢性肝病患者拉米夫定耐药毒株突变模式特征分析[J].中华实验和临床病毒学杂志,2017,31(1):31-34.
[9]Wani H U,Al Kaabi S,Sharma M,et al.High dose of lamivudine and resistance in patients with chronic hepatitis B[J].Hepat Res Treat,2014:615621.
[10]Hou J L,Gao Z L,Xie Q,et al.Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks:a randomized controlled trial[J].J Viral Hepat,2015,22(2):85-93.
[11]Ma Z J,Li Q,Wang J B,et al.Combining oxymatrine or matrine with lamivudine increased its antireplication effect against the hepatitis B virus in vitro[J].Evid Based Complement Alternat Med,2013:186573.
[12]唐海峰,朱素楠.苦参碱联合胸腺肽对慢性乙型肝炎患者血清Foxo3 a、INF-α、HBV-DNA水平及T细胞亚群的影响[J].海南医学,2017,28(7):1055-1058.
[2]Park J H,Jung S W,Park N H,et al.Efficacy of tenofovir-based rescue therapy in lamivudine-resistant chronic hepatitis B patients with failure of lamivudine and adefovir combination[J].Clin Ther,2015,37(7):1433-1442.
[3]戚敬虎,鞠金昌,徐雷,等.富马酸替诺福韦二吡呋酯单药治疗拉米夫定耐药慢性乙型肝炎的疗效观察[J].中华肝脏病杂志,2016,24(4):307-309.
[4]邓海洋,谢鸿恩,扶伟霞.替比夫定联合苦参碱注射液治疗慢性乙型肝炎的临床疗效[J].中国医药指南,2014,12(7):99-100.
[5]Wang X,Lin H,Zhang R.The clinical efficacy and adverse effects of interferon combined with matrine in chronic hepatitis B:a systematic review and metaanalysis[J].Phytother Res,2017,31(6):849-857.
[6]中华医学会肝病学分会.慢性乙型肝炎诊断标准(2015年版)[J].中西医结合肝病杂志,2015,25(6):384.
[7]中华医学会肝病学分会.慢性乙型肝炎防治指南[J].中华肝脏病学杂志,2005,13(12):881-891.
[8]欧阳雅博,李庆,魏飞力,等.慢性肝病患者拉米夫定耐药毒株突变模式特征分析[J].中华实验和临床病毒学杂志,2017,31(1):31-34.
[9]Wani H U,Al Kaabi S,Sharma M,et al.High dose of lamivudine and resistance in patients with chronic hepatitis B[J].Hepat Res Treat,2014:615621.
[10]Hou J L,Gao Z L,Xie Q,et al.Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks:a randomized controlled trial[J].J Viral Hepat,2015,22(2):85-93.
[11]Ma Z J,Li Q,Wang J B,et al.Combining oxymatrine or matrine with lamivudine increased its antireplication effect against the hepatitis B virus in vitro[J].Evid Based Complement Alternat Med,2013:186573.
[12]唐海峰,朱素楠.苦参碱联合胸腺肽对慢性乙型肝炎患者血清Foxo3 a、INF-α、HBV-DNA水平及T细胞亚群的影响[J].海南医学,2017,28(7):1055-1058.