脂肪酸与非酒精性脂肪性肝病：病例对照研究和随机对照试验的荟萃分析。

Fatty acid and non-alcoholic fatty liver disease: Meta-analyses of case-control and randomized controlled trials.

机构信息

Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.

Institute of Nutrition and Health, Qingdao University, Qingdao, China.

出版信息

Clin Nutr. 2018 Feb;37(1):113-122. doi: 10.1016/j.clnu.2017.01.003. Epub 2017 Jan 16.

DOI:10.1016/j.clnu.2017.01.003

PMID:28161092

Abstract

BACKGROUND AND AIMS

Blood and/or liver fatty acid contents of healthy subjects and non-alcoholic fatty liver disease (NAFLD) patients have shown inconsistent associations. In addition, the results of randomized controlled trials (RCTs) in relation to the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver fat, triglyceride (TAG) and fasting glucose levels are inconsistent. The present study aimed to investigate the differences of fatty acid content in the blood and/or liver tissue between healthy subjects and NAFLD patients, and to quantify the benefits of n-3 PUFA therapy in NAFLD patients.

METHODS

A systematic literature search was performed up to November 2016 using PubMed and Scopus databases. The differences of fatty acid content between cases and controls were calculated as weighted mean differences (WMD) by using a random-effects model. The intervention effects of RCTs were calculated as WMD for net changes in ALT, AST, liver fat, TAG and fasting glucose levels, respectively. Meta-regression with restricted maximum likelihood estimation was used to evaluate a potential linear relationship between confounding factors and effect sizes. Generalized least square was performed for dose-response analysis.

RESULTS

Ten eligible case-control studies and 11 RCTs were included. The pooled estimates of case-control studies showed that blood and/or liver docosahexaenoic acid (DHA) content was significantly higher in the controls compared with cases. The pooled estimates of RCTs showed that n-3 PUFA supplementation significantly reduced the ALT (-7.53 U/L; 95% CI: -9.98, -5.08 U/L), ASL (-7.10 U/L, 95% CI: -11.67, -2.52 U/L) and TAG (-36.16 mg/dL, 95% CI: -49.15, -23.18 mg/dL) concentrations, and marginally reduced the liver fat content (-5.11%, 95% CI: -10.24, 0.02%, P = 0.051), but not fasting glucose. Dose-response analysis of RCTs showed that 1 g per day increment of eicosapentaenoic acid (EPA)+DHA was associated with a 3.14 U/L, 2.43 U/L, 2.74% and 9.97 mg/dL reduction in ALT (95% CI: -5.25, -1.02 U/L), AST (95% CI: -3.90, -0.90 U/L), liver fat (95% CI: -4.32, -1.16%) and TAG (95% CI: -14.47, -5.48 mg/dL) levels, respectively.

CONCLUSIONS

The present meta-analysis provides substantial evidence that n-3 PUFA supplementation, especially DHA, has a favorable effect in treatment of NAFLD.

摘要

背景与目的

健康受试者和非酒精性脂肪性肝病（NAFLD）患者的血液和/或肝脏脂肪酸含量显示出不一致的关联。此外，关于 n-3 多不饱和脂肪酸（PUFA）补充对丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、肝脂肪、三酰甘油（TAG）和空腹血糖水平影响的随机对照试验（RCT）的结果也不一致。本研究旨在探讨健康受试者和 NAFLD 患者之间血液和/或肝组织中脂肪酸含量的差异，并量化 n-3 PUFA 治疗对 NAFLD 患者的益处。

方法

使用 PubMed 和 Scopus 数据库进行了系统的文献检索，检索截至 2016 年 11 月。使用随机效应模型计算病例与对照组之间脂肪酸含量的差异，计算加权均数差（WMD）。使用 WMD 分别计算 RCT 的干预效果，以净变化 ALT、AST、肝脂肪、TAG 和空腹血糖水平。使用受限极大似然估计进行元回归，以评估混杂因素与效应大小之间的潜在线性关系。进行广义最小二乘法进行剂量反应分析。

结果

纳入了 10 项符合条件的病例对照研究和 11 项 RCT。病例对照研究的汇总估计表明，对照组的血液和/或肝脏二十二碳六烯酸（DHA）含量明显高于病例组。RCT 的汇总估计表明，n-3 PUFA 补充显著降低 ALT（-7.53 U/L；95% CI：-9.98，-5.08 U/L）、AST（-7.10 U/L，95% CI：-11.67，-2.52 U/L）和 TAG（-36.16 mg/dL，95% CI：-49.15，-23.18 mg/dL）浓度，并适度降低肝脂肪含量（-5.11%，95% CI：-10.24，0.02%，P = 0.051），但对空腹血糖没有影响。RCT 的剂量反应分析表明，每天增加 1 g 二十碳五烯酸（EPA）+DHA 与 ALT（95% CI：-5.25，-1.02 U/L）、AST（95% CI：-3.90，-0.90 U/L）、肝脂肪（95% CI：-4.32，-1.16%）和 TAG（95% CI：-14.47，-5.48 mg/dL）的降低分别相关。