恩替卡韦联合复方鳖甲软肝片治疗乙型肝炎肝硬化患者疗效及转归研究
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摘要
目的研究应用恩替卡韦(ETV)联合复方鳖甲软肝片治疗乙型肝炎肝硬化患者的疗效及其对疾病转归的影响。方法 2014年1月～2016年12月我院收治的乙型肝炎肝硬化患者76例,采用随机数字表法将患者分为对照组36例和观察组40例,分别给予ETV或ETV联合复方鳖甲软肝片治疗,观察12 m月。采用PCR法定量检测血清HBV DNA载量,采用放射免疫法检测血清透明质酸(HA)、Ⅲ型前胶原(PⅢP)、层粘连蛋白(LN)和Ⅳ型胶原(CⅣ),常规行血生化和Fibroscan检查。结果在治疗12 m末,观察组血清TBIL为(19.7±13.4)μmol/L,ALT水平为(28.3±9.4) U/L,均显著低于对照组的[(23.2±13.8)μmol/L和(53.6±10.2) U/L,P<0.05],观察组血清ALB水平为(37.2±5.6)g/L,PTA为(91.1±11.2)%,显著高于对照组[(34.7±6.1)g/L和(81.4±10.5)%,P<0.05];观察组CTP评分为(6.3±1.2),显著低于对照组的[(8.1±1.4),P<0.05],肝脏硬度检测(LSM)为(16.5±12.2) kPa,也显著低于对照组的[(22.7±14.4) kPa,P<0.05];观察组血清HA水平为(89.2±43.1)μg/L,PⅢP为(119.7±60.8)μg/L,LN为(98.7±30.2)μg/L,CⅣ为(102.6±29.7)μg/L,均低于对照组[分别为(184.3±58.2)μg/L、(254.5±74.7)μg/L、(140.8±39.7)μg/L、(165.7±41.2)μg/L,P<0.05];观察组血清HBVDNA阴转率为97.5%(39/40),与对照组的94.4%(34/36)比,差异无统计学意义(P>0.05),观察组血清HBV DNA载量为(3.2±0.3)log10 copies/ml,与对照组的(3.5±0.4)log10 copies/ml比,无显著性差异(P>0.05);观察组腹水、肝性脑病、消化道出血和肝细胞癌发生率分别为17.5%、5.0%、10.0%和2.5%,显著低于对照组的52.7%、13.8%、16.7%和11.1%(P<0.05);在观察的12 m内,观察组无死亡病例,而对照组死亡3例(8.3%)。结论应用ETV联合复方鳖甲软肝片治疗能够明显改善乙型肝炎肝硬化患者肝功能指标,降低血清肝纤维化指标,改善预后。
Objective To investigate the efficacy of entecavir(ETV) and Fufang Biejiaruanganpian,a Chinese herbal medicine compound,combination therapy in patients with hepatitis B-induced liver cirrhosis.Methods 76 patients with hepatitis B liver cirrhosis were recruited in our hospital between January 2014 and December 2016. The patients with liver cirrhosis were randomly divided into control group(n=36) and observation group(n =40),receiving ETV or ETV and Fufang Biejiaruangan combination therapy,and all patients were followed-up for 12 months. Serum HBV DNA loads were detected by PCR,and serum HA,PⅢP,LN and CⅣlevels were assayed routinely. All patients received Fibroscan check-up. Results At the end of 12 month observation,serum bilirubin and ALT levels in the observation group were(19.7±13.4) μmol/L and(28.3±9.4) U/L,much lower than [(23.2±13.8) μmol/L and(53.6±10.2)U/L,P<0.05] in the control,and serum albumin level was(37.2±5.6) g/L,prothrombin time activity(PTA) was(91.1±11.2)%,much higher than [(34.7±6.1)g/L and(81.4±10.5)%,P<0.05] in the control;the CTP score was(6.3±1.2),much lower than [(8.1 ±1.4),P<0.05]in the control,and liver stiffness measurement(LSM)was(16.5±12.2) kPa,also much lower than [(22.7±14.4)kPa,P<0.05] in the control;serum HA level was(89,2±43.1) μg/L,PⅢP level was(119.7±60.8) μg/L,LN level was(98.7±30.2) μg/L,and CIV level was(102.6±29.7) μg/L,significantly lower than [(184.3±58.2) μg/L,(254.5±74.7) μg/L,(140.8±39.7) μg/L,and(165.7±41.2) μg/L,respectively,P<0.05] in the control;serum HBV DNA loss was 97.5%(39/40),and it was94.4%(34/36) in the control,without significant difference between the two groups(P>0.05),and serum HBV DNA load was(3.2±0.3) log10 copies/ml,no significant difference as compared to(3.5±0.4) log10 copies/ml in the control(P >0.05);the incidences of ascites,hepatic encephalopathy,gastrointestinal bleeding and hepatocellular carcinoma in the observation group were 17.5%,5.0%,10.0% and 2.5%,much lower than 52.7%,13.8%,16.7% and11.1%(P<0.05) in the control;no one in the observation group but three patients(8.3%) in the control died within the 12 month observation. Conclusion The combination of ETV and Fufang Biejiaruangan compound therapy in patients with hepatitis B-induced liver cirrhosis might improve liver functions,alleviate liver cirrhosis,and improve the prognosis,which needs further and long-term investigation.
Objective To investigate the efficacy of entecavir(ETV) and Fufang Biejiaruanganpian,a Chinese herbal medicine compound,combination therapy in patients with hepatitis B-induced liver cirrhosis.Methods 76 patients with hepatitis B liver cirrhosis were recruited in our hospital between January 2014 and December 2016. The patients with liver cirrhosis were randomly divided into control group(n=36) and observation group(n =40),receiving ETV or ETV and Fufang Biejiaruangan combination therapy,and all patients were followed-up for 12 months. Serum HBV DNA loads were detected by PCR,and serum HA,PⅢP,LN and CⅣlevels were assayed routinely. All patients received Fibroscan check-up. Results At the end of 12 month observation,serum bilirubin and ALT levels in the observation group were(19.7±13.4) μmol/L and(28.3±9.4) U/L,much lower than [(23.2±13.8) μmol/L and(53.6±10.2)U/L,P<0.05] in the control,and serum albumin level was(37.2±5.6) g/L,prothrombin time activity(PTA) was(91.1±11.2)%,much higher than [(34.7±6.1)g/L and(81.4±10.5)%,P<0.05] in the control;the CTP score was(6.3±1.2),much lower than [(8.1 ±1.4),P<0.05]in the control,and liver stiffness measurement(LSM)was(16.5±12.2) kPa,also much lower than [(22.7±14.4)kPa,P<0.05] in the control;serum HA level was(89,2±43.1) μg/L,PⅢP level was(119.7±60.8) μg/L,LN level was(98.7±30.2) μg/L,and CIV level was(102.6±29.7) μg/L,significantly lower than [(184.3±58.2) μg/L,(254.5±74.7) μg/L,(140.8±39.7) μg/L,and(165.7±41.2) μg/L,respectively,P<0.05] in the control;serum HBV DNA loss was 97.5%(39/40),and it was94.4%(34/36) in the control,without significant difference between the two groups(P>0.05),and serum HBV DNA load was(3.2±0.3) log10 copies/ml,no significant difference as compared to(3.5±0.4) log10 copies/ml in the control(P >0.05);the incidences of ascites,hepatic encephalopathy,gastrointestinal bleeding and hepatocellular carcinoma in the observation group were 17.5%,5.0%,10.0% and 2.5%,much lower than 52.7%,13.8%,16.7% and11.1%(P<0.05) in the control;no one in the observation group but three patients(8.3%) in the control died within the 12 month observation. Conclusion The combination of ETV and Fufang Biejiaruangan compound therapy in patients with hepatitis B-induced liver cirrhosis might improve liver functions,alleviate liver cirrhosis,and improve the prognosis,which needs further and long-term investigation.
引文
[1] Foucher J,Chanteloup E,Vergniol J,et al. Diagnosis of cirrhosis by transient elastography(FibroScan):a prospective study. Gut,2006,55(3):403.
[2] Kettaneh A,Marcellin P,Douvin C,et al. Features associated with success rate and performance of fibroscan measurements for the diagnosis of cirrhosis in HCV patients:a prospective study of 935 patients. J Hepatol,2007,46(4):628-634.
[3] Simsek H,Schiffe E,Goodman Z,et al. 513 effects of entecavir and lamivudine on advanced liver fibrosis after 48 weeks of treatment in patients with CHB infection:Results of three pivotal trials. J Hepatol,2006,44(6):S191.
[4]张宁,肖小河,周双男,等.复方鳖甲软肝片对乙型肝炎血清纤维化标志物作用的Meta分析.实用肝脏病杂志,2012,15(6):524-526.
[5]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.
[6] Salkic NN,Jovanovic P,Hauser G,et al. FibroTest/Fibrosure forsignificant liver fibrosis and cirrhosis in chronic hepatitis B:a meta-analysis. Am J Gastroenterol,2014,109(6):796.
[7] Alghamdi AS. Fibroscan:a noninvasive test of liver fibrosis assessment. Saudi J Gastroenterol,2007,13(3):147-149.
[8] Friedrich-Rust M, M ii Her C, Winckler A, et al. Assessment of liver fibrosis and steatosis in PBC with fibroScan, MRI,MR-spectroscopy, and serum markers. J Clin Gastroenterol,2010,44(1):58-65.
[9] Poynard T,De LV,Zarski JP,et al. Relative performances of fibroTest, fibroscan, and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis C:a step toward the truth in the absence of a gold standard. J Hepatol, 2012,56(3):541-548.
[10] Maor Y,Halfon P,Bashari D,et al. Fibrotest or fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C. Haemophilia,2010,16(1):148-154.
[11] Wong GL, Wong VW, Choi PC, et al. On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients. Antivir Ther,2011,16(2):165.
[12] Zhu CL,Li WT,Li Y,et al. Serum levels of tissue inhibitor of metalloproteinase—1 are correlated with liver fibrosis in patients with chronic hepatitis B. J Dig Dis,2012,13(11):558-563.
[13] Zhou D,Dong MU,Jiang M,et al. Hepatoprotective effect of juglone on dimethylnitrosamine-induced liver fibrosis and its effect on hepatic antioxidant defence and the expression levels ofα-SMA and collagen III. Mol Med Rep,2015,12(3):4095-4102.
[14] Guo SG,Zhang W,Jiang T,et al. Influence of serum collected from rat perfused with compound Biejiaruangan drug on hepatic stellate cells. World J Gastroenterol,2004, 10(10):1487-1494.
[15]吴刚,何鸿雁,李烨,等.复方鳖甲软肝片联合恩替卡韦对HBV相关肝硬化患者的临床疗效观察.中华肝脏病杂志,2014,22(8):604-608.
[16]姚云洁,杨才兴,巫继.恩替卡韦联合复方鳖甲软肝片治疗慢性乙型肝炎患者疗效观察.实用肝脏病杂志,2015,18(4):356-359.
[17] Chen J, Liu C, Chen H,et al. Study on noninvasive laboratory tests for五fibrosis in chronic HBV infection and their evaluation. J Clin Lab Anal,2013,27(1):5-11.
[18]程孟怀,邵鸣,吴青芳.恩替卡韦联合复方鳖甲软肝片治疗乙型肝炎肝硬化患者疗效观察.实用肝脏病杂志,2010,13(3):207-208.
[19] Mcmahon MA,Jilek BL,Brennan TP,et al. The anti-hepatitis B drug entecavir inhibits HIV-1 replication and can select HIV-1 variants resistant to antiretroviral drugs. N Engl J Med,2007,356(25):2614.
[20] Zhang DW,Wang JF,Niu JZ,et al. Experimental study on effect of compound Biejia Ruangan prescription on high-resolution computerized tomographic images in bleomycin induced pulmonary fibrosis rats. Chin J Integr Med,2003,9(4):270-275.
[2] Kettaneh A,Marcellin P,Douvin C,et al. Features associated with success rate and performance of fibroscan measurements for the diagnosis of cirrhosis in HCV patients:a prospective study of 935 patients. J Hepatol,2007,46(4):628-634.
[3] Simsek H,Schiffe E,Goodman Z,et al. 513 effects of entecavir and lamivudine on advanced liver fibrosis after 48 weeks of treatment in patients with CHB infection:Results of three pivotal trials. J Hepatol,2006,44(6):S191.
[4]张宁,肖小河,周双男,等.复方鳖甲软肝片对乙型肝炎血清纤维化标志物作用的Meta分析.实用肝脏病杂志,2012,15(6):524-526.
[5]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.
[6] Salkic NN,Jovanovic P,Hauser G,et al. FibroTest/Fibrosure forsignificant liver fibrosis and cirrhosis in chronic hepatitis B:a meta-analysis. Am J Gastroenterol,2014,109(6):796.
[7] Alghamdi AS. Fibroscan:a noninvasive test of liver fibrosis assessment. Saudi J Gastroenterol,2007,13(3):147-149.
[8] Friedrich-Rust M, M ii Her C, Winckler A, et al. Assessment of liver fibrosis and steatosis in PBC with fibroScan, MRI,MR-spectroscopy, and serum markers. J Clin Gastroenterol,2010,44(1):58-65.
[9] Poynard T,De LV,Zarski JP,et al. Relative performances of fibroTest, fibroscan, and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis C:a step toward the truth in the absence of a gold standard. J Hepatol, 2012,56(3):541-548.
[10] Maor Y,Halfon P,Bashari D,et al. Fibrotest or fibroscan for evaluation of liver fibrosis in haemophilia patients infected with hepatitis C. Haemophilia,2010,16(1):148-154.
[11] Wong GL, Wong VW, Choi PC, et al. On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients. Antivir Ther,2011,16(2):165.
[12] Zhu CL,Li WT,Li Y,et al. Serum levels of tissue inhibitor of metalloproteinase—1 are correlated with liver fibrosis in patients with chronic hepatitis B. J Dig Dis,2012,13(11):558-563.
[13] Zhou D,Dong MU,Jiang M,et al. Hepatoprotective effect of juglone on dimethylnitrosamine-induced liver fibrosis and its effect on hepatic antioxidant defence and the expression levels ofα-SMA and collagen III. Mol Med Rep,2015,12(3):4095-4102.
[14] Guo SG,Zhang W,Jiang T,et al. Influence of serum collected from rat perfused with compound Biejiaruangan drug on hepatic stellate cells. World J Gastroenterol,2004, 10(10):1487-1494.
[15]吴刚,何鸿雁,李烨,等.复方鳖甲软肝片联合恩替卡韦对HBV相关肝硬化患者的临床疗效观察.中华肝脏病杂志,2014,22(8):604-608.
[16]姚云洁,杨才兴,巫继.恩替卡韦联合复方鳖甲软肝片治疗慢性乙型肝炎患者疗效观察.实用肝脏病杂志,2015,18(4):356-359.
[17] Chen J, Liu C, Chen H,et al. Study on noninvasive laboratory tests for五fibrosis in chronic HBV infection and their evaluation. J Clin Lab Anal,2013,27(1):5-11.
[18]程孟怀,邵鸣,吴青芳.恩替卡韦联合复方鳖甲软肝片治疗乙型肝炎肝硬化患者疗效观察.实用肝脏病杂志,2010,13(3):207-208.
[19] Mcmahon MA,Jilek BL,Brennan TP,et al. The anti-hepatitis B drug entecavir inhibits HIV-1 replication and can select HIV-1 variants resistant to antiretroviral drugs. N Engl J Med,2007,356(25):2614.
[20] Zhang DW,Wang JF,Niu JZ,et al. Experimental study on effect of compound Biejia Ruangan prescription on high-resolution computerized tomographic images in bleomycin induced pulmonary fibrosis rats. Chin J Integr Med,2003,9(4):270-275.