鱼油补充对非酒精性脂肪性肝病患者 miRNA-122、FGF-21 浓度及肝纤维化的影响：一项随机、双盲、安慰剂对照临床试验研究方案。

Effect of fish oil supplementation on the concentration of miRNA-122, FGF-21 and liver fibrosis in patients with NAFLD: Study protocol for a randomized, double-blind and placebo-controlled clinical trial.

机构信息

Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Carlos Chagas Filho Avenue, 367/CCS - Block J2, University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil; School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.

School of (M)edicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Prof. Rodolpho Paulo Rocco Street, 255 - University City-Ilha Do Fundão, Rio de Janeiro, RJ, Brazil.

出版信息

Clin Nutr ESPEN. 2023 Oct;57:117-125. doi: 10.1016/j.clnesp.2023.06.027. Epub 2023 Jun 28.

DOI:10.1016/j.clnesp.2023.06.027

PMID:37739645

Abstract

BACKGROUND & AIMS: To date, no specific drugs are available for non-alcoholic fatty liver disease (NAFLD), though the effect of fish oil supplementation on improving fibrosis in patients with NAFLD has been evaluated. N-3 polyunsaturated fatty acids (n-3 PUFA) may modulate the concentration of microRNAs (miRNAs) and fibroblast growth factor (FGF)-21, which have been identified as non-invasive markers of liver fibrosis. The present study aims to evaluate whether n-3 PUFA supplementation can modulate miRNA-122 and FGF-21 and improve liver fibrosis and steatosis, measured by transient hepatic elastography (THE), in individuals with NAFLD.

METHODS

A randomized, double-blind, placebo-controlled clinical trial will be conducted to evaluate the effect of 4 g/day supplementation of fish oil (2100 mg EPA and 924 mg DHA) in patients with NAFLD over a 6-month period. Fifty-two patients aged >19 years will be randomly assigned to either a placebo (olive oil) or treatment (fish oil) group. Anthropometric data, food intake, physical activity, body composition, resting energy expenditure (evaluated using indirect calorimetry), liver enzymes, platelets, lipids and glucose profile, inflammatory markers (such as C-reactive protein, neutrophil/lymphocyte, platelet/lymphocyte, and monocyte/lymphocyte ratios), miRNA-122 and FGF-21 concentration, and incorporation of fatty acids into the erythrocyte membrane (analyzed using gas chromatography) as well as the degree of liver fibrosis and steatosis assessed using THE (Fibroscan® Touch 502, Paris, France) and liver biomarkers Steato-Brazilian Longitudinal Study of Adult Health, Fatty Liver Index, NAFLD Fibrosis Score, Fibrosis-4 score, and FibroScan-AST score will be evaluated at the beginning and end of the treatment. Continuous variables with normal distribution will be compared between placebo and intervention groups using Student's T test for independent samples; continuous non-parametric variables will be compared using Dunn or Mann-Whitney test. Associations between categorical variables will be analyzed using the chi-square test, and within-group differences will be evaluated using the Wilcoxon signed-ranks test. The criterion for determining significance will be set at 5%.

CONCLUSION

The present study protocol will investigate the supplementation of EPA-rich fish oil as an alternative treatment for NAFLD and its feasibility in affecting the concentration of miRNA-122 and FGF-21 markers. Its findings will offer valuable contributions to the literature.

REGISTRATION

ReBEC number RBR-8dp876.

摘要

背景与目的

迄今为止，尚无专门针对非酒精性脂肪性肝病（NAFLD）的药物，但已评估了鱼油补充剂对改善 NAFLD 患者纤维化的作用。n-3 多不饱和脂肪酸（n-3 PUFA）可能调节微 RNA（miRNA）和成纤维细胞生长因子（FGF）-21 的浓度，这些标志物已被确定为肝纤维化的非侵入性标志物。本研究旨在评估 n-3 PUFA 补充是否可以调节 miRNA-122 和 FGF-21，并通过瞬时肝弹性成像（THE）改善 NAFLD 个体的肝纤维化和脂肪变性。

方法

将进行一项随机、双盲、安慰剂对照的临床试验，以评估在 6 个月内每天补充 4 g 鱼油（2100 mg EPA 和 924 mg DHA）对 NAFLD 患者的影响。将 52 名年龄>19 岁的患者随机分配至安慰剂（橄榄油）或治疗（鱼油）组。评估人体测量数据、食物摄入、身体活动、身体成分、静息能量消耗（间接热量法评估）、肝酶、血小板、血脂和血糖谱、炎症标志物（如 C 反应蛋白、中性粒细胞/淋巴细胞、血小板/淋巴细胞、单核细胞/淋巴细胞比值）、miRNA-122 和 FGF-21 浓度以及红细胞膜中脂肪酸的掺入（气相色谱法分析），以及使用 THE（Fibroscan®Touch 502，巴黎，法国）评估肝纤维化和脂肪变性程度以及肝生物标志物巴西成人健康纵向研究的脂肪肝指数、NAFLD 纤维化评分、纤维化-4 评分和 FibroScan-AST 评分，在治疗开始和结束时进行评估。正态分布的连续变量将使用独立样本学生 t 检验在安慰剂和干预组之间进行比较；连续非参数变量将使用 Dunn 或 Mann-Whitney 检验进行比较。分类变量之间的关联将使用卡方检验进行分析，组内差异将使用 Wilcoxon 符号秩检验进行评估。确定显著性的标准设定为 5%。