美他多辛治疗酒精性肝病的多中心、随机、双盲、安慰剂平行对照的临床研究

Capsule metadoxine in the treatment of alcoholic liver disease： A randomized, double-blind, placebocontrolled, multicenter study

目的观察美他多辛胶囊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，254例酒精性肝病患者按1：1的比例随机进入试验组（美他多辛胶囊组）或安慰剂组。试验组：口服美他多辛胶囊每次500mg，每日3次；安慰剂组：口服美他多辛模拟胶囊每次2粒，每日3次。治疗疗程为6周，停药后2周随访。治疗期间患者每3周随访1次。治疗前、治疗第3、6周、停药后2周观察症状体征、肝肾功能、血常规、尿常规；治疗前、治疗第6周时对部分患者进行CT检查。对研究过程戒酒和不戒酒患者分层进行生物化学疗效评估。根据数据资料不同分别采用珊佥验、X^2检验、方差分析等方法进行统计学分析。结果254例患者进入本研究，试验组126例，安慰剂组128例。治疗6周后，试验组ALT、AST、γ-谷氨酰转肽酶中位数分别由治疗前的80．0、59．2、123．0U／L显著下降为治疗结束时的41．1、36．0、57．0U／L，其改善程度均分别显著优于安慰剂组，F值分别为2．689、2．567、3．097，P值均〈0．05，差异有统计学意义。戒酒患者治疗6周后，试验组血清生物化学改善的总有效率为82．8％，显著优于安慰剂组的55．7％，P=0．0000。不戒酒患者治疗6周后，试验组血清生物化学改善的总有效率为65．4％，安慰剂组为44．8％，P=0．1767，差异无统计学意义。治疗后试验组肝／脾CT比值显著提高（P=0．0023），但组间比较差异无统计学意义（P=0．6293）。试验组和安慰剂组不良反应发生率分别为1．6％和1．6％，两组间比较，P=1．000，差异无统计学意义。结论美他多辛胶囊可以安全、有效地治疗酒精性肝病。

Objective To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease. Methods A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy. Results 254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L （before treatment） to 41.1 U/L, 36.0 U/L, 57.0 U/L （after 6 weeks therapy）.The improvement in liver function was more significant in metadoxine group than in placebo group （P 〈 0.05）. For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group （55.7%, P = 0.0000）. For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group （44.8%, P = 0.1767）. The CT value ratio of liver to spleen was significantly improved in metadoxine group （P = 0.0023 ）, and there was no significant difference between the two groups （P = 0.6293）. The rate of adverse was 1.6% in both of groups. Conclusion Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.