牛磺熊去氧胆酸与熊去氧胆酸治疗肝硬化的临床效果比较

Clinical effects of tauroursodeoxycholic acid vs ursodeoxycholic acid in treatment of liver cirrhosis

目的:与已知治疗肝硬化有效药物熊去氧胆酸(ursodeoxycholic acid,UDCA)(商品名:优思弗)进行比较,评估牛磺熊去氧胆酸(tauroursodeoxycholic acid,TUDCA)(商品名:滔罗特)治疗肝硬化患者的安全性及有效性.方法:2011-06/2014-01于华中科技大学同济医学院协和医院及湖北省新华医院门诊或病房收集肝硬化患者48例,所有符合入选条件的患者填写知情同意书后随机分为TUDCA组(实验组)和UDCA组(对照组),其中实验组有4例在治疗前后均自愿接受肝活检,对照组有2例治疗前后接受肝活检.实验组口服TUDCA胶囊15 mg/(kg·d),对照组按相同剂量口服UDCA,治疗6 mo.观察记录服药期间患者临床症状、生化及组织学的变化,以评估疗效.结果:试验共纳入48例肝硬化患者,试验期间脱落及退出5例,43例完成药物观察,其中实验组21例,对照组22例.治疗前两组患者性别组成、病因分类、年龄及生化学指标无明显差异,在治疗3 mo时,实验组:谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、γ谷氨酰转移酶(γ-glutamyl transferase,GGT)及白蛋白较前明显改善,治疗前后具有统计学意义;对照组:AST及白蛋白较治疗前明显改善,治疗前后具有明显统计学意义;在治疗6 mo时,实验组血清AST、ALP、GGT和白蛋白较治疗前有明显改善,治疗前后差异具有统计学意义(P<0.05);对照组血清ALT、GGT和白蛋白水平有明显改善,治疗前后差异具有统计学意义(P<0.05);而且,治疗结束时实验组ALP、AST下降较对照组明显,具有明显统计学意义(P<0.05);实验组两例肝穿患者中有2例肝穿组织学分别由治疗前G2S3、G3S2转变为G2S1、G2S1,另外2例组织学治疗前后无明显变化,对照组两例治疗前后组织学无明显变化;两组肝纤维化指标较治疗前均降低,但差异无统计学意义;两组血常规、肾功能、血沉、大小便常规及电解质水平较治疗前无明显变化,无统计学意义;两种治疗耐受性良好,治疗过程中无明显不良反应发生.结论:口服TUDCA[15 mg/(kg·d)]能改善改善肝硬化患者的肝功能指标,尤其是改善胆汁淤积指标水平,并可能延缓患者的肝纤维化进程,是治疗肝硬化患者安全有效的药物,其作用可能略优于UDCA.

AIM： To evaluate the efficacy and safety of tauroursodeoxycholic acid（TUDCA） vs ursodeoxycholic acid（UDCA） in patients with liver cirrhosis.METHODS： Forty-eight patients with cirrhosis treated at Wuhan Union Hospital and Hubei Province Xinhua Hospital were enrolled. The patients were randomly divided into either a TUDCA group or a UDCA group. The TUDCA group had four cases receiving liver biopsy and the UDCA group had two cases. Both drugs were administered at a daily dose of 15 mg/（kg·d） in a randomly assigned sequence for a 6 mo period. Clinical, biochemical and histological features were recorded before and after the treatments to assess the clinical effects of TUDCA. RESULTS： Forty-three patients were included in the final analysis. The TUDCA group had 21 patients and the UDCA group had 22 patients. Before treatment, there were no significant differences in age, sex or blood chemistry parameters between the two groups. After three months of treatment, serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, γ-glutamyl transferase（GGT） and alkaline phosphatase（ALP） levels in the TUDCA group while only AST level in the UDCA group significantly reduced from baseline（P 〈 0.05）. Serum albumin levels significantly increased in both groups（P 〈 0.05）, and serum AST levels decreased more significantly in the TUDCA group than in the UDCA group. After 6 mo of treatment, serum AST, GGT and ALP levels in the TUDCA group while ALT and GGT levels in the UDCA group significantly reduced from baseline（P 〈 0.05）. Serum albumin levels significantly increased in both groups（P 〈 0.05）. Moreover, serum AST and ALP levels in the TUDCA group decreased more significantly than those in the UDCA group. Two patients in the TUDCA group had significant histological relief. Both treatments were well tolerated, and there was no side effect associated with treatment. CONCLUSION： TUDCA [15 mg/（kg·d）] therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of biochemical parameters. TUDCA may delay the progression of liver fibrosis.