噻唑烷二酮类胰岛素增敏剂临床治疗非酒精性脂肪性肝病疗效及安全性Meta分析

目的 综合评价噻唑烷二酮类(TZDs)胰岛素增敏剂治疗非酒精性脂肪性肝病(NAFLD)患者临床疗效及安全性.方法 通过检索Medline、PubMed、Ovid、解放军医学图书馆以及CBM Disc、CNKI、万方、维普等英、中文全文数据库,并结合手工检索方式收集1998年至2008年公开发表的有关TZDs治疗NAFLD临床对照试验资料,严格制定入选及排除标准,采用RevMan 4.2软件包对数据进行Meta分析,结合森林图与漏斗图对合并统计量进行检验、敏感性分析和发表偏倚分析.结果 18项临床对照试验共473例患者纳入本研究,综合分析TZDs对于NAFLD患者血清ALT、AST、TC、TG及体重指数(BMI)、胰岛素抵抗指数的影响,合计加权平均数(WMD)值(95% CI)分别为32.24(18.98～45.49)(Z=4.77,P<0.05)、20.32(2.30～38.35)(Z=2.21,P<0.05)、0.26(-0.01～0.54)(Z=1.88,P=0.06)、0.63(0.33～0.93)(Z=4.14,P<0.01)、-0.06(-0.66～0.55)(Z=0.19,P=0.85)和2.63(1.33～3.93)(Z=3.96,P<0.01).其中6篇文献通过不同方法观察到共104例NAFLD患者接受TZDs治疗前后肝组织病理改变,显示此类药物可显著改善非酒精性脂肪性肝炎(NASH)患者肝细胞脂肪变性、炎症、纤维化[WMD值(95% CI)分别为1.59(1.08～2.10)、1.45(0.90～2.00)、0.72(0.12～1.32),Z值分别为6.08、5.16、2.33,P均<0.05),尤其是NASH活动指数[WMD值(95% CI)为4.21(3.13～5.28),Z=7.66,P<0.01].其中应用TZDs治疗后共7例患者退出试验,其主要不良反应包括:乏力、头晕、下肢水肿、体重增加及消化道反应、肝酶升高等,但与对照组比较差异并无统计学意义.结论 TZDs胰岛素增敏剂治疗NAFLD疗效确切,其不仅明显改善肝脏血清酶学、血脂、胰岛素抵抗指数及肝组织病理程度,且无严重不良反应,临床应用安全、有效.

Clinical efficiency and safety of thiazolidinediones on treatment of patients with nonalcoholic fatty fiver disease: A Meta analysis

Objective To evaluate the clinical efficiency and safety of thiazolidinediones (TZDs) on treat-ment of patients with nonalcoholic fatty liver disease (NAFLD). Methods The published controlled clinical trials about TZDs on treatment of patients with NAFLD from 1998 to 2008 were identified by searching in the full-text data base,such as Medline, PubMed, Ovid, EMCC, CBM Disc, CNKI, Wanfang, Weipu data and so on, as well as by searching of cross references from original articles and reviews. The enrollment standard was formulated strictly ac-cording to the designs of trials, and Meta analysis was performed by software package of Review Manage 4.2. Further-more, the statistic test, sensitivity and publication bias about the combined statistic data were revealed by referring to forest-graph and funnel-plot. Results All of the 473 patients in 18 controlled clinical trials were enrolled in this study. The weighted mean diffrerence of serum ALT, AST,TC,TG and BMI, HOMA-IR before and after treatment with TZDs 32. 24 (18.98-45.49) (Z=4.77,P<0.05),20.32 (2.30-38.35) (Z=2.21,P<0.05),0.26 (-0.01-0.54)(Z=1.88,P=0.06),0.63 (0.33-0.93) (Z=4.14,P<0.01),and -0.06 (-0.66-0.55) (Z=0.19, P=0.85),2.63 (1.33-3.93) (Z=3.96, P<0.01). In all papers, the improvement of hepatic tissue after treatment with TZDs in patients with NAFLD was observed in only 6 articles, which demonstrated the hepatic steatosis, inflammation and fibrosis [WMD (95% CI) 1.59 (1.08-2.10), 1.45 (0.90-2.00), 0.72 (0.12-1.32), Z= 6.08,5.16,2.33,P<0.05],especially the degree of NASH activity index,whose WMD (95% CI) was 4.21 (3.13-5.28) and Z=7.66,P<0.01, were improved significantly in the 104 NASH patients taken this kinds of drugs. There were 7 patients exiting from the all chnical trial, and the main adverse effects in patients accepting treat-ment with TZDs were debility, dizziness, edema of lower extremity, weight gain, indisposition of gastrointestinal tract, elevated liver enzyme and so on, which were similar to the control group. Conclusions The therapeutic effects of TZDs on NAFLD is confirmed. Not only are the serum liver enzyme,TC,TG and HOMA-IR in patients with NAFLD improved, but this new euglycemic agent has no acutely adverse effect in clinical application,which confirms the clin-ical efficiency and safety of TZDs on treatment of patients with NAFLD.