二甲双胍与维生素E治疗非酒精性脂肪性肝病的系统评价

摘要

目的：比较二甲双胍与维生素E治疗非酒精性脂肪性肝病（NAFLD）的疗效及不良反应的差异。方法检索PubMed、EMbase、Cochrane Library、Web of Science、中国知网、万方数据库、维普及中国生物医学文献数据库（CBM）2014年4月10日前发表的有关二甲双胍与维生素E治疗NAFLD的随机对照试验（RCT），对符合纳入标准的临床研究进行Meta分析。结果共纳入4篇RCT，3篇为英文，1篇为中文。Meta分析结果显示，有效率：口服二甲双胍与口服维生素E后的血清ALT变化量相比，二甲双胍的有效率更高（P＜0．0001）；口服二甲双胍与口服维生素E后的血清AST、身体质量指数（BMI）、空腹血糖、甘油三酯的变化量差异均无统计学意义（P值分别为0．30、0．39、0．82、0．74）；二甲双胍治疗后的肝活组织检查脂肪变性得分变化量、小叶炎性得分变化量及气球样改变不如口服维生素E后的变化量。安全性：二甲双胍能够有效降低患者血清ALT和GGT水平，而不会造成肝细胞损伤（P值分别为0．008、0．01）。不良反应发生率：仅1篇文献报道二甲双胍组患者出现轻微腹泻及腹痛、腹部不适，差异无统计学意义。结论二甲双胍较维生素E可明显降低NAFLD患者的血清ALT水平，维生素E在改善肝细胞活组织检查结果方面优于二甲双胍，而二者在降低AST、BMI、空腹血糖、甘油三酯方面差异无统计学意义。由于所纳入的原始文献和患者数量有限，且存在选择性偏倚和实施偏倚，期待有更高质量的随机双盲对照试验提供有效证据。%Objective To compare the clinical efficacy and adverse effects of metformin versus vitamin E in the treatment of nonalcoholic fatty liver disease (NAFLD).Methods Randomized controlled trials (RCTs)of NAFLD treatment with metformin and vitamin E,which were published before April 10,2014,were retrieved from international and domestic biomedical databases including the PubMed,EMbase,Co-chrane Library,Web of Science,CNKI,WANFANG,VIP,and CBM.Clinical trials that met the inclusion criteria were chosen for meta-a-nalysis.Results Four RCTs were included,of which three were published in English and one in Chinese.Meta-analysis data showed that metformin had a significantly higher effective rate than vitamin E in terms of serum alanine aminotransferase (ALT)alternation post oral treat-ment (P<0.0001).There were no significant differences in body mass index (BMI)and serum aspartate aminotransferase (AST),fasting blood glucose (FBG),and triglyceride (TG)levels post oral treatment (P=0.30,0.39,0.82,and 0.74,respectively).Liver biopsy showed that after metformin treatment,the alterations in fatty degeneration and lobular inflammation scores,as well as balloon-like changes, were less than those post vitamin E treatment.Regarding clinical safety,metformin effectively reduced serum ALT and gamma-glutamyl trans-ferase levels without causing hepatocyte damage (P=0.008 and 0.01,respectively).Only one RCT mentioned the occurrence of mild diarrhea and abdominal pain or discomfort in the metformin group,but there was no significant difference from the vitamin group.Conclusion Among NAFLD patients,metformin reduces serum ALT levels more significantly than vitamin E,while the latter has its advantage in improving the re-sults of liver biopsy.However,these two drugs have no significant differences in reducing BMI and AST,FBG,and TG levels.This study in-cluded limited numbers of original references and patients,and it might involve selection and implementation biases.RCTs of higher quality are expected to provide more effective evidence for assessing the clinical efficacy and adverse reactions of metformin versus vitamin E.