美他多辛片治疗酒精性肝病的多中心、随机、双盲、安慰剂平行对照临床研究

Metadoxine in the treatment of alcoholic liver disease: A randomized double-blind placebo-controlled multicenter study

目的评价美他多辛片治疗酒精性肝病的临床疗效和安全性。方法采用多中心、随机、双盲、安慰剂平行对照的临床研究,240例酒精性肝病患者按1∶1的比例随机进入试验组(美他多辛片剂组)或安慰剂组。试验组口服美他多辛片每次500mg,每日3次;安慰剂组口服美他多辛模拟片每次1片,每日3次。疗程为6周,治疗期间患者每3周随访1次。治疗前、治疗第3、6周观察症状体征、血常规、尿常规和肝肾功能;治疗前、治疗第6周时进行B超检查。对研究过程中戒酒和不戒酒患者分层进行临床、生化和影像学疗效评估。结果219例患者按方案完成研究,其中试验组114例,安慰剂组105例。戒酒患者治疗6周后,试验组血清3项生化指标均有显著改善(P均<0.05),其中丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)改善显著优于安慰剂组(P值分别为0.0357和0.0015),天冬氨酸氨基转移酶(AST)改善两组无显著差异(P=0.0672);试验组血清生化改善的总有效率为80.00%,显著优于安慰剂组的57.58%(P=0.0018)。不戒酒患者治疗6周后,试验组治疗前后血清3项生化指标均有显著改善(P均<0.05),安慰剂组治疗前后仅ALT(P=0.0012)显著改善,组间比较试验组的ALT、AST、GGT改善均显著优于安慰剂组(P均<0.05);试验组血清生化改善的总有效率为75.00%,显著优于安慰剂组的43.75%(P=0.0024)。无论戒酒与否,影像学脂肪肝程度改善的总有效率试验组略高于安慰剂组,但两组无统计学差异。试验组和安慰剂组不良反应发生率分别为1.72%和0.90%,两组间比较无显著差异(P=1.000)。结论美他多辛片可安全、有效地治疗酒精性肝病。

Objective To evaluate the efficacy and safety of Metadoxine in treatment of alcoholic liver disease. Methods It was a randomized,double blind,placebo-controlled,muhicenter clinical study. 240 patients were randomizly entered either Metadoxine group or placebo group in 1 ： 1 ratio. Patients in Metadoxine group received Metadoxine 500 mg tid po. Patients in placebo group received placebo 1 tid po. The course was 6 weeks. Patients visited once every 3 weeks. Clinical symptoms and liver function test were evaluated in all patients before treatment, at the 3^th week and at the end of therapy. Ultrasound examinations were performed in all patients before treatment and at the end of therapy. Efficacy evaluation was independent to the patients who stopped drinking or not during the study. Results 219 patients completed the study according to the protocol, 114 in Metadoxine group and 105 in placebo group. For patients who stopped drinking during the study, significant improvement of liver function test was found in Metadoxine group after 6 weeks therapy （ P 〈 0.05）, alanine aminotransferase （ALT） ,T-glutamyltr ansfernase （GGT） improvement were significantly higher than placebo group （ P =0.035 7,0.001 5）. The total effective rate of liver function test was 80.00% in Metadoxine group, much higher than 57.58% of that in placebo group（ P = 0.001 8）. For patients who did not stop drinking during the study, significant improvement of liver function test was found in Metadoxine group after 6 weeks therapy（ P 〈 0.05）, only aspartic aminotransferase （AST） improvement was found in placebo group（ P = 0.001 2）, ALT,AST,GGT improvement in Metadoxine group were significantly higher than that of placebo group（ P 〈 0.05）. The total effective rate of liver function test was 75.00% in Metadoxine group, much higher than 43.75% of that in placebo group （P = 0.002 4）. The total effective rate of Ultrasound improvement was little better in Metadoxine group with no significant difference statistically. The rate of adverse events in Metadoxine group and placebo group were 1.72% and 0.90% （ P = 1.000）. Conclusion Metadoxine is effective and safe in treatment of alcoholic liver disease.