Non-alcoholic Steatohepatitis Versus Simple Hepatic Steatosis: Is There a Difference in the Nutritional Factors Influencing Lipid Perioxidation and Inflammation?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 205
- 试验地点
- 1
- 主要终点
- Hepatic fatty acid composition in total lipids in liver biopsy
研究概览
简要总结
The first aim of this study is to assess oxidative stress and nutritional status in patients with elevated liver enzymes who were found to have either simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) or normal histological findings on liver biopsy by measuring liver lipid peroxides and tumor necrosis factor (TNF)-α, liver pathology and immunohistochemistry, liver function tests, liver and red blood cell membrane fatty composition, insulin resistance (IR) parameters, plasma lipid peroxides, plasma antioxidant vitamins and antioxidant power, lipid profile, subject demographics, medical history and medication use. The second aim is to detect differences in hepatic gene expression (messenger RNA, mRNA) and epigenetic regulation (micro RNA, miRNA) between patients with SS or NASH and healthy controls, in addition to determine in patients with non-alcoholic fatty liver disease (NAFLD = SS+NASH combined) whether there is an association between hepatic n-3 PUFA content and gene expression. The third aim is to determine the intestinal microbiome (microbial composition and metagenome) in patients with SS or NASH and healthy controls.
详细描述
NASH is associated with obesity, diabetes and hyperlipidemia. Fat accumulation in the liver is likely due to variable degrees of disordered fatty-acid metabolism and insulin resistance (IR). Liver steatosis, especially polyunsaturated fatty acids (PUFA) in the liver, increases lipid peroxidation and is associated with a reduction in the antioxidant defense system. This oxidative stress can lead to increased production of pro-inflammatory cytokines (TNF-α, transforming growth factor-beta) contributing to the development of steatohepatitis and fibrosis.TNF-α - may further contribute to IR. In addition, changes in fatty acid composition within the liver may influence lipid metabolism and inflammation. In particular, n-3 PUFA have an effect on the insulin sensitivity, transcription of antioxidant genes, inflammatory response and production of reactive oxygen species. Differences might be seen on the gene expression level (mRNA) and also in epigenetic regulation (miRNA).
Microbiota composition might influence energy metabolism, and inflammatory tone and IR through increased endotoxemia and therefore could also play a role in the development of NAFLD.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Hepatic fatty acid composition in total lipids in liver biopsy
时间窗: Baseline
Gas chromatography
Hepatic gene expression
时间窗: Baseline
mRNA by microarray
Intestinal microbiota composition
时间窗: Baseline
Illumina 16S technology
次要结局
- Lipid peroxides in the liver(Baseline)
- Hepatic liver antioxidant power(Baseline)
- Hepatic microRNA expression in the liver(Baseline)
- Short-chain fatty acids in stool(Baseline)
- Intestinal microbiota - specific organisms and groups(Baseline)
- Intestinal microbiome on a genetic level(Baseline)
- Plasma endotoxin(Baseline)
研究者
Johane Allard
Prof. Dr.
University Health Network, Toronto