水飞蓟素胶囊联合阿德福韦酯、拉米夫定治疗对失代偿期乙肝肝硬化患者肝功能及血清病毒学指标的影响
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摘要
目的:观察水飞蓟素胶囊联合阿德福韦酯、拉米夫定治疗对失代偿期乙型病毒性肝炎(乙肝)肝硬化患者肝功能及血清病毒学指标的影响。方法:选取2015年9月至2017年9月安徽宿州皖北煤电集团总医院收治的90例失代偿期乙肝肝硬化患者,按随机数字表法分为研究组和对照组,每组45例。对照组采用阿德福韦酯联合拉米夫定治疗,研究组在对照组的基础上加用水飞蓟素胶囊治疗。比较两组治疗前和治疗12周、24周、48周后肝功能指标、血清病毒学指标及Child-Pugh评分。结果:随着治疗时间延长,两组谷丙转氨酶(ALT)、总胆红素(TBil)、谷草转氨酶(AST)、乙型肝炎病毒(HBV)DNA水平及ChildPugh评分逐渐降低,白蛋白(ALB)水平和凝血酶原活动度(PTA)逐渐升高,且研究组各指标改善程度均优于对照组(均P<0.05)。治疗48周后,两组HBeAg转阴率、HBV DNA<1 000copies/mL比率均上升,且研究组高于对照组(P<0.05)。结论:水飞蓟素胶囊联合阿德福韦酯、拉米夫定可抑制HBV复制,改善失代偿期乙肝肝硬化患者的肝功能。
Objective:To investigate the effect of silymarin capsule combined with adefovir dipivoxil and lamivudine on the liver function and serum virology of patients with decompensated hepatitis B cirrhosis.Methods:A total of 90 patients with decompensated hepatitis B liver cirrhosis who were admitted to our hospital from September 2015 to September 2017 were selected,and randomly divided into a study group and a control group,with 45 cases in each group.The patients in the control group received adefovir dipivoxil combined with lamivudine treatment,and those in the study group were treated as the control group with addition of silymarin capsule.The liver function,serum virological parameters and HBV DNA level after 12,24,and 48 weeks of treatment were compared between the two groups.Results:After treatment,the alanine aminotransferase(ALT),total bilirubin(TBil),aspartate transaminase(AST)and hepatitis B virus(HBV)DNA levels in serum and Child-Pugh score in both groups were decreased,while the albumin(ALB)level and prothrombin activity(PTA)were increased(P<0.05).These changes were more marked in the study group.After 48 weeks of treatment,HBeAg negative rate and the proportion of HBV DNA<1 000 copies/mL were higher in the study group than those in the control group(P<0.05).Conclusion:Silymarin capsule combined with adefovir dipivoxil and lamivudine could effectively inhibit HBV replication and improve the liver function of patients with decompensated hepatitis B cirrhosis.
Objective:To investigate the effect of silymarin capsule combined with adefovir dipivoxil and lamivudine on the liver function and serum virology of patients with decompensated hepatitis B cirrhosis.Methods:A total of 90 patients with decompensated hepatitis B liver cirrhosis who were admitted to our hospital from September 2015 to September 2017 were selected,and randomly divided into a study group and a control group,with 45 cases in each group.The patients in the control group received adefovir dipivoxil combined with lamivudine treatment,and those in the study group were treated as the control group with addition of silymarin capsule.The liver function,serum virological parameters and HBV DNA level after 12,24,and 48 weeks of treatment were compared between the two groups.Results:After treatment,the alanine aminotransferase(ALT),total bilirubin(TBil),aspartate transaminase(AST)and hepatitis B virus(HBV)DNA levels in serum and Child-Pugh score in both groups were decreased,while the albumin(ALB)level and prothrombin activity(PTA)were increased(P<0.05).These changes were more marked in the study group.After 48 weeks of treatment,HBeAg negative rate and the proportion of HBV DNA<1 000 copies/mL were higher in the study group than those in the control group(P<0.05).Conclusion:Silymarin capsule combined with adefovir dipivoxil and lamivudine could effectively inhibit HBV replication and improve the liver function of patients with decompensated hepatitis B cirrhosis.
引文
[1]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(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
[2]BOETTLER T,THIMME R.Antiviral therapy in hepatitis B virus-associated liver cirrhosis[J].Dig Dis,2015,33(4):608-612.
[3]张伟,许荣放,田锐锋,等.阿德福韦酯与替比夫定联合恩替卡韦对失代偿期乙肝肝硬化患者肝功能及血清病毒学指标的影响[J].解放军医学杂志,2016,41(12):1041-1044.
[4]涂燕云,陈海艳,刘旭东.乙型肝炎肝硬化失代偿期抗病毒治疗的研究进展[J].临床肝胆病杂志,2015,31(3):460-464.
[5]KIM M N,PARK J Y,AHN S H,et al.Durability of the virological response after lamivudine discontinuation in lamivudine-resistant patients with a complete virological response after lamivudine and adefovir combination therapy[J].Journal of Medical Virology,2016,89(1):85-90.
[6]李雨,马宁,邓姣,等.拉米夫定联合阿德福韦酯与恩替卡韦单药治疗拉米夫定耐药慢性乙肝患者疗效的Meta分析[J].中国循证医学杂志,2015(5):573-580.
[7]中华医学会肝病学分会.慢性乙型肝炎防治指南(2010年版)[J].中华内科杂志,2011,3(2):66-82.
[8]林春蕾,王岩,李涛,等.接受抗病毒治疗的代偿期乙肝肝硬化患者进展为肝癌的危险因素分析[J].山东医药,2017,57(32):81-83.
[9]ZHANG K,CAO H,LIANG J,et al.CONSORT:Effects of adding adefovirdipivoxil to peginterferon alfa-2a at different time points on HBeAg-positivepatients:a prospective,randomized study[J].Medicine,2016,95(31):e4471.
[10]XIANG X,ZHONG J H,KE Y,et al.Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection[J].Journal of Clinical Oncology,2017,35(4suppl):257.
[11]KARAKAYA F,OZER S,KALKAN C,et al.Discontinuation of lamivudine treatment in HBeAg-negative chronic hepatitis B:apilot study with long-term followup[J].Antiviral Therapy,2017,22(7):559.
[12]PAN C Q,YI W,LIU M,et al.Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B[J].Journal of Viral Hepatitis,2017,24(3):246-252.
[13]黄娟娟,刘世坤,李佐军,等.拉米夫定和水飞蓟素对酒精刺激的HBV转基因小鼠肝纤维化相关因子的影响[J].中南大学学报(医学版),2017,42(3):257-263.
[14]LEE S,AHN S H,JUNG K S,et al.Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance[J].Journal of Hepatology,2016,64(2):S595.
[15]黄静,龙子江,李丽,等.水飞蓟宾胶囊对酒精性肝纤维化大鼠的保护作用[J].中成药,2016,38(2):229-234.
[16]KAMEL R O.Interactions between mefloquine and the anti-fibrotic drug silymarin on Schistosoma mansoni infections in mice[J].Journal of Helminthology,2016,90(6):760-765.
[17]梁守赞,黄惠宜.恩替卡韦与水飞蓟宾胶囊联合治疗慢性乙型肝炎患者临床效果分析[J].实用肝脏病杂志,2018,21(2):208-211.
[18]RUI S,YAN J,ZHANG H,et al.Intermediatestage hepatocellular carcinoma patients with a high HBV-DNA load may benefit from postoperative antihepatitis B virus therapy[J].Medicine,2017,96(30):e7608.
[19]赵振纲,冯珉.水飞蓟素对慢性丙型肝炎患者的护肝和抗病毒作用[J].肝脏,2013(10):703-704.
[20]KE L I,MINGCHUAN L I,LAB D.Effects of entecavir combined with silymarin on inflammatory markers and oxidative stress level in patients with hepatitis B virus-related decompensated liver cirrhosis[J].China Pharmacy,2018,54(3):520-529.
[2]BOETTLER T,THIMME R.Antiviral therapy in hepatitis B virus-associated liver cirrhosis[J].Dig Dis,2015,33(4):608-612.
[3]张伟,许荣放,田锐锋,等.阿德福韦酯与替比夫定联合恩替卡韦对失代偿期乙肝肝硬化患者肝功能及血清病毒学指标的影响[J].解放军医学杂志,2016,41(12):1041-1044.
[4]涂燕云,陈海艳,刘旭东.乙型肝炎肝硬化失代偿期抗病毒治疗的研究进展[J].临床肝胆病杂志,2015,31(3):460-464.
[5]KIM M N,PARK J Y,AHN S H,et al.Durability of the virological response after lamivudine discontinuation in lamivudine-resistant patients with a complete virological response after lamivudine and adefovir combination therapy[J].Journal of Medical Virology,2016,89(1):85-90.
[6]李雨,马宁,邓姣,等.拉米夫定联合阿德福韦酯与恩替卡韦单药治疗拉米夫定耐药慢性乙肝患者疗效的Meta分析[J].中国循证医学杂志,2015(5):573-580.
[7]中华医学会肝病学分会.慢性乙型肝炎防治指南(2010年版)[J].中华内科杂志,2011,3(2):66-82.
[8]林春蕾,王岩,李涛,等.接受抗病毒治疗的代偿期乙肝肝硬化患者进展为肝癌的危险因素分析[J].山东医药,2017,57(32):81-83.
[9]ZHANG K,CAO H,LIANG J,et al.CONSORT:Effects of adding adefovirdipivoxil to peginterferon alfa-2a at different time points on HBeAg-positivepatients:a prospective,randomized study[J].Medicine,2016,95(31):e4471.
[10]XIANG X,ZHONG J H,KE Y,et al.Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection[J].Journal of Clinical Oncology,2017,35(4suppl):257.
[11]KARAKAYA F,OZER S,KALKAN C,et al.Discontinuation of lamivudine treatment in HBeAg-negative chronic hepatitis B:apilot study with long-term followup[J].Antiviral Therapy,2017,22(7):559.
[12]PAN C Q,YI W,LIU M,et al.Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B[J].Journal of Viral Hepatitis,2017,24(3):246-252.
[13]黄娟娟,刘世坤,李佐军,等.拉米夫定和水飞蓟素对酒精刺激的HBV转基因小鼠肝纤维化相关因子的影响[J].中南大学学报(医学版),2017,42(3):257-263.
[14]LEE S,AHN S H,JUNG K S,et al.Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance[J].Journal of Hepatology,2016,64(2):S595.
[15]黄静,龙子江,李丽,等.水飞蓟宾胶囊对酒精性肝纤维化大鼠的保护作用[J].中成药,2016,38(2):229-234.
[16]KAMEL R O.Interactions between mefloquine and the anti-fibrotic drug silymarin on Schistosoma mansoni infections in mice[J].Journal of Helminthology,2016,90(6):760-765.
[17]梁守赞,黄惠宜.恩替卡韦与水飞蓟宾胶囊联合治疗慢性乙型肝炎患者临床效果分析[J].实用肝脏病杂志,2018,21(2):208-211.
[18]RUI S,YAN J,ZHANG H,et al.Intermediatestage hepatocellular carcinoma patients with a high HBV-DNA load may benefit from postoperative antihepatitis B virus therapy[J].Medicine,2017,96(30):e7608.
[19]赵振纲,冯珉.水飞蓟素对慢性丙型肝炎患者的护肝和抗病毒作用[J].肝脏,2013(10):703-704.
[20]KE L I,MINGCHUAN L I,LAB D.Effects of entecavir combined with silymarin on inflammatory markers and oxidative stress level in patients with hepatitis B virus-related decompensated liver cirrhosis[J].China Pharmacy,2018,54(3):520-529.