恩替卡韦联合水飞蓟素对乙型病毒性肝炎失代偿期肝硬化患者炎症指标及氧化应激水平的影响

Effects of Entecavir Combined with Silymarin on Inflammatory Markers and Oxidative Stress Level in Patients with Hepatitis B Virus-related Decompensated Liver Cirrhosis

目的:前瞻性研究恩替卡韦联合水飞蓟素对乙型病毒性肝炎失代偿期肝硬化患者炎症指标及氧化应激水平的影响。方法:将2015年1月-2016年8月武汉科技大学医院收治的85例乙型病毒性肝炎失代偿期肝硬化患者按单双号随机分为对照组(42例)和观察组(43例)。对照组患者给予恩替卡韦0.5 mg,qd;观察组在对照组基础上给予水飞蓟素140 mg,tid。两组患者疗程均为48周。观察两组患者治疗后血清乙型肝炎病毒(HBV)DNA、HBV e抗原(HBeAg)阴转率,比较两组患者治疗前后血清肝功能指标[胆红素(TBil)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)]、炎症指标[白细胞介素18(IL-18)、IL-8、肿瘤坏死因子α(TNF-α)]水平和Child-pugh评分,以及氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)]水平变化,并记录其不良反应发生情况。结果:治疗前,两组患者血清肝功能指标、炎症指标和氧化应激指标水平差异均无统计学意义(P>0.05);给药48周后,观察组患者血清HBV DNA、HBe Ag阴转率高于对照组,但组间差异无统计学意义(P>0.05)。与治疗前比较,给药48周后两组患者血清中肝功能指标水平、Child-pugh评分、炎症指标以及MDA、NO水平均显著降低(P<0.05),SOD水平显著升高(P<0.05),且观察组上述指标改善程度高于对照组(P<0.05)。对照组和观察组不良反应发生率差异无统计学意义(P>0.05),停药后均好转。结论:恩替卡韦联合水飞蓟素可通过抑制炎症反应、减轻氧化应激反应而改善乙型病毒性肝炎失代偿期肝硬化患者的肝功能;且两药联用效果优于恩替卡韦单用。

ABSTRACT OBJECTIVE： To prospectively study the effects of entecavir combined with Silymarin on the inflammatory markers and oxidative stress level in patients with hepatitis B virus-related decompensated liver cirrhosis （HBV-DLC）. METHODS： A total of 85 HBV-DLC patients in Hospital of Wuhan Technology University during Jan. 2015-Aug. 2016 were divided into control group （42 cases） and observation group （43 cases） according to the single and double number random. Control group was given entecavir 0.5 mg, qd. Observation group was additionally given Silymarin capsules 140 mg, tid, on the basis of control group. Both groups were treated for 48 weeks. After treatment, HBV DNA and HBeAg negative conversion rate were observed. The levels of liver func- tion indexes （TBil, AST, ALT）, the Child-pugh score and levels of inflammatory indexes （IL-18, IL-8, TNF-ct）, the levels of ox- idative stress indexes （MDA, SOD, NO） were compared between 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS： Before treatment, there was no statistical significance in liver function indexes, inflammatory factors or oxida- tive stress indexes of 2 groups （P〉0.05）. After treatment for 48 weeks, serum HBV DNA and HBeAg negative conversion rate of observation group were higher than those of control group, but without statistical significance （P〉0.05）. Compared with before treatment, liver function indexes levels, Child-pugh score, inflammatory indexes, MDA and NO levels of 2 groups were decreased significantly after treatment for 48 weeks （P〈0.05）, while SOD level was decreased significantly （P〈0.05） ; the degree of improvement of above indexes in observation group was higher than control group （P〈0.05）. There was no statistical significance in the incidence of ADR between control group and observation group （P〈0.05）, and both were improved after drug withdrawal. CONCLUSIONS： Entecavir combined with Silymarin can inhibit inflammatory reaction and relieve oxidative stress reaction to im- tgrove the liver function of HBV-DLC patients： dm~ combination better than entecavir alone.