替比夫定联合复方牛胎肝提取物治疗慢性乙型肝炎患者疗效及安全性评价*

doi:10.3969/j.issn.1672-5069.2017.06.012

摘要/Abstract

摘要： 目的评价替比夫定联合复方牛胎肝提取物治疗慢性乙型肝炎（CHB）患者的疗效及安全性。方法将87例CHB患者随机分为对照组44例和观察组43例。给予对照组口服替比夫定600 mg,1次/ d,观察24 w;观察组在对照组治疗的基础上,给予口服复方牛胎肝提取物片80 mg,3次/d,观察24 w。比较两组患者治疗前后肝功能、肾功能、透明质酸（HA）、层粘蛋白（LN）、 Ⅳ型胶原（Ⅳ-C）、Ⅲ型前胶原氨端肽（PⅢNP）和肌酸激酶（CK）变化情况,以及HBV DNA和HBeAg转阴率和不良反应发生率。结果在治疗24 w末,观察组血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平分别（25.4±8.5） U/L、（23.8±6.5） U/L,显著低于对照组的【（46.3±9.3） U/L、（49.0±7.3） U/L,P<0.05】;观察组血清HA、LN、Ⅳ-C、PⅢNP水平分别为（128.4±83.2） μg/L、（88.4±64.3） μg/L、（64.4±49.0） μg/L、（112.3±73.8）μg/L,显著低于对照组的【（249.3±82.1） μg/L、（163.1±55.1） μg/L、（98.2±50.3） μg/L、（183.2±63.2） μg/L,P<0.01】;两组血清HBV DNA和HBeAg转阴率和不良反应发生率无显著差异。结论替比夫定联合复方牛胎肝提取物片治疗CHB患者,可显著改善肝功能和肝纤维化指标,且安全性良好。

关键词: 慢性乙型肝炎, 替比夫定, 复方牛胎肝提取物, 治疗

Abstract: Objective To investigate the efficacy and safety of combined therapy of telbivudine and compound embryonic bovine liver extract in patients with chronic hepatitis B（CHB）. Methods Eighty-seven patients with chronic hepatitis B were randomly divided into combination treatment group （n=43） and control group（n=44）. Patients in combination treatment group were treated with compound embryonic bovine liver extract plus telbivudine,and those in control group were treated with telbivudine alone. The data of liver function index,renal function index,serum hyaluronic acid （HA）,laminin （LN）,type IV collagen（IV-C）,type III procollagen,N-terminal peptide（P IIINP）,creatine kinase（CK）,HBV DNA undetectable rates,HBeAg loss rates and adverse reaction rates were compared between the two groups. Results At the end of 24 weeks of treatment,serum alanine transaminase （ALT）,aspartate aminotransferase （AST） levels in combination treatment group were（25.4±8.5） U/L,（23.8±6.5） U/L,respectively,significantly lower than those in control group [（46.3±9.3） U/L,（49.0±7.3）U/L,P<0.05];serum HA,LN,Ⅳ-C,PⅢNP levels in combination treatment group were（128.4±83.2） μg/L,（88.4±64.3） μg/L,（64.4±49.0） μg/L,（112.3±73.8） μg/L,respectively,significantly lower than those in control group[（249.3±82.1） μg/L,（163.1±55.1） μg/L,（98.2±50.3） μg/L,（183.2±63.2） μg/L,P<0.01];serum HBV DNA undetectable,HBeAg loss and adverse reaction rates in the two groups were not significantly different（P>0.05）. Conclusions Telbivudine combined with compound embryonic bovine liver extract can significantly improve the liver function and liver fibrosis in patients with CHB,and have a good safety profile.

Key words: Chronic hepatitis B, Telbivudine, Compound embryonic bovine liver extract, Therapy

张宿荣, 叶晓光, 陈志伟. 替比夫定联合复方牛胎肝提取物治疗慢性乙型肝炎患者疗效及安全性评价*[J]. 实用肝脏病杂志, 2017, 20(6): 684-687.

Zhang Surong, Ye Xiaoguang, Chen Zhiwei. Clinical efficacy and safety of combination therapy of telbivudine and compound embryonic bovine liver extract in patients with chronic hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(6): 684-687.

参考文献

[1] Ott JJ,Stevens GA,Groeger J, et al. Global epidemiology of hepatitis B virus infection:new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine,2012,30（12）:2212-2219.
[2] Lu FM,Zhuang H. Management of hepatitis B in China. Chin Med J （Engl）,2009,122（1）:3-4.
[3] EASL clinical practice guidelines:Management of chronic hepatitis B virus infection. J Hepatol,2012,57（1）:167-185.
[4] 叶俊钊,王伟,廖冰,等. 实时剪切波弹性成像诊断慢性乙型肝炎肝纤维化的影响因素. 实用医学杂志,2016,32（15）:2454-2458.
[5] Bedossa P. Reversibility of hepatitis B virus cirrhosis after therapy:who and why Liver Int,2015,35（Suppl 1）:78-81.
[6] 王自林,蒋智勇,牛作铭,等. 阿德福韦酯联合复方牛胎肝提取物治疗慢性乙型肝炎患者临床观察.实用肝脏病杂志,2012,15（1）:42-43.
[7] 赵乾,吴新慈. 拉米夫定联合复方牛胎肝提取物治疗肝纤维化的临床疗效及安全性评价. 中国临床药理学杂志,2015,23（12）:1088-1090.
[8] 黄红丽,胡志文,聂玉强,等. 复方牛胎肝提取物联合恩替卡韦治疗慢性乙型肝炎疗效分析. 实用肝脏病杂志,2014,17（1）:41-44.
[9] Mallat A,Lotersztajn S. Cellular mechanisms of tissue fibrosis. 5. Novel insights into liver fibrosis. Am J Physiol Cell Physiol,2013,305（8）:C789-799.
[10] Lim YS,Kim WR. The global impact of hepatic fibrosis and end-stage liver disease. Clin Liver Dis,2008,12（4）:733-746,vii.
[11] 张佩婷,张文洁,左长京,等. 促肝细胞生长素治疗肝纤维化的临床应用进展. 中国生化药物杂志,2016,21（7）:209-212.
[12] 杨瑞华,李芹,陈玮. 扶正化瘀胶囊治疗慢性乙型肝炎肝纤维化疗效的Meta分析. 中华肝脏病杂志,2015,23（4）:295-296.
[13] 杨年欢,袁国盛,周宇辰,等. 恩替卡韦联合复方鳖甲软肝片治疗慢性乙型肝炎肝纤维化96周的临床疗效.南方医科大学学报,2016,36（6）:775-779.
[14] Hayasaka A,Saisho H. Serum markers as tools to monitor liver fibrosis. Digestion,1998,59（4）:381-384.
[15] 李新月,孙燕,向德栋. 血清Ⅲ型前胶原、Ⅳ型胶原、透明质酸及层粘蛋白对肝纤维化的评估价值.中西医结合肝病杂志,2002,12（4）:235-236.
[16] 余晓红,曹军平,王平,等. 乙肝患者血清肝纤维化检测与肝穿病理结果的相关性. 河北医药,2016,32（1）:106-107.
[17] Li F,Zhu CL,Zhang H,et al. Role of hyaluronic acid and laminin as serum markers for predicting significant fibrosis in patients with chronic hepatitis B. Braz J Infect Dis,2012,16（1）:9-14.
[18] Gressner OA,Weiskirchen R,Gressner AM. Biomarkers of liver fibrosis:clinical translation of molecular pathogenesis or based on liver-dependent malfunction tests. Clin Chim Acta,2007,381（2）:107-113.
[19] 李谦,张玉杰,施光峰,等. 复方牛胎肝提取物片治疗肝纤维化的多中心研究. 中华肝脏病杂志,2007,15（10）:749-752.
[20] 王牡丹,曹海军,李善高,等. 复方牛胎肝提取物联合抗病毒治疗对肝硬化患者肝纤维化指标的影响分析.中国生化药物杂志,2015,21（11）:147-148,151.
[21] 何杰雄,王鹏,李静. 复方牛胎肝提取物治疗非酒精性脂肪性肝炎临床观察. 实用肝脏病杂志,2016,19（5）:557-560.
[22] 中华医学会肝病学分会和感染病学分会. 慢性乙型肝炎防治指南（2015年版）. 实用肝脏病杂志,2016,19（3）：Ⅴ-ⅩⅩⅢ.
[23] 俞萍,黄利华,丁虹,等. 恩替卡韦治疗前后慢性乙型肝炎患者的肝组织学变化. 中华传染病杂志,2010,28（2）:120-122.
[24] 金清龙,王崇,闫红青,等. 乙型肝炎抗病毒治疗中拉米夫定及替比夫定对血清生化学和病毒学及肝脏组织学的影响.中国全科医学,2010,13（36）:4069-4071.