Dong Yajie, Lv Qingguo, Li Sheyu, Wu Yuan, Li Ling, Li Juan, Zhang Fang, Sun Xin, Tong Nanwei
Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, No. 37 Guoxue Road, Chengdu, Sichuan 610041, China.
Chinese Evidence-Based Medicine Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Clin Res Hepatol Gastroenterol. 2017 Jun;41(3):284-295. doi: 10.1016/j.clinre.2016.11.009. Epub 2017 Jan 5.
New drugs are urgently needed for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The aim of this meta-analysis was to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in NAFLD/NASH.
We searched the MEDLINE, Embase, and Cochrane Library Central to identify randomized controlled trials (RCTs) and observational studies that compared GLP-1RAs with a control treatment or baseline values with respect to efficacy and safety in patients with NAFLD/NASH. Mean differences (MDs) with 95% confidence intervals (CIs) and odds ratios (ORs) were pooled using a random-effect model.
Six studies were eligible and included. Among the 329 NAFLD/NASH patients included in these studies, 277 patients had type 2 diabetes (T2D). GLP-1RA treatment produced significant reductions relative to baseline in liver histology scores for steatosis (MD, 0.80; 95% CI, 0.49 to 1.11), lobular inflammation (MD, 0.22; 95% CI, 0.00 to 0.45), hepatocellular ballooning (MD, 0.41; 95% CI, 0.15 to 0.67) and fibrosis (MD, 0.35; 95% CI, 0.00 to 0.70). Compared with placebo and positive agents, GLP-1RAs significantly reduced gamma-glutamyl transpeptidase (GGT) levels (MD, 13.8 U/L; 95% CI, 7.4 to 20.3; P<0.001). The reported major adverse events associated with GLP-1RA treatment included mild to moderate gastrointestinal discomfort that resolved within a few weeks.
Our study suggests that in NASH patients, particularly patients with diabetes, GLP-1RAs may improve liver histology and reduce aminotransferase levels from baseline. Benefits of GLP-1RAs are considered to outweigh the risks in NAFLD/NASH patients with or without diabetes.
治疗非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）迫切需要新型药物。本荟萃分析旨在评估胰高血糖素样肽-1受体激动剂（GLP-1RAs）治疗NAFLD/NASH的疗效和安全性。
检索MEDLINE、Embase和Cochrane图书馆中心，以识别比较GLP-1RAs与对照治疗或基线值在NAFLD/NASH患者疗效和安全性方面的随机对照试验（RCTs）和观察性研究。采用随机效应模型汇总95%置信区间（CIs）的平均差（MDs）和比值比（ORs）。
六项研究符合纳入标准并被纳入。在这些研究纳入的329例NAFLD/NASH患者中，277例患有2型糖尿病（T2D）。相对于基线，GLP-1RA治疗使肝组织学脂肪变性评分显著降低（MD，0.80；95%CI，0.49至1.11），小叶炎症评分显著降低（MD，0.22；95%CI，0.00至0.45），肝细胞气球样变评分显著降低（MD，0.41；95%CI，0.15至0.67），纤维化评分显著降低（MD，0.35；95%CI，0.00至0.70）。与安慰剂和阳性药物相比，GLP-1RAs显著降低γ-谷氨酰转肽酶（GGT）水平（MD，13.8 U/L；95%CI，7.4至20.3；P<0.001）。报告的与GLP-1RA治疗相关的主要不良事件包括轻度至中度胃肠道不适，数周内可缓解。
我们的研究表明，在NASH患者中，尤其是糖尿病患者，GLP-1RAs可能改善肝组织学并使转氨酶水平较基线降低。在患有或未患有糖尿病的NAFLD/NASH患者中，GLP-1RAs的益处被认为大于风险。
