未经证实:非酒精性脂肪性肝病(NAFLD)是一种进行性肝病,具有潜在的严重并发症,包括肝硬化和肝细胞癌。以前,我们已经确定了与肝脏脂肪含量和非酒精性脂肪性肝炎(NASH)相关的循环脂质特征.这里,我们开发了NAFLD光谱的代谢组学图谱,定义脂肪变性的相互关联的代谢特征(非酒精性脂肪肝,NASH,和纤维化)。
UNASSIGNED:我们对来自欧洲NAFLD注册患者(n=627)的血清样本中的分子脂质和极性代谢物进行了质谱分析,代表NAFLD的全部范围。使用各种单变量,多变量,和机器学习统计方法,我们从三个临床角度询问了代谢物:脂肪变性,NASH,和纤维化。
未经证实:NAFLD代谢网络生成后,我们确定了脂肪变性特有的15种代谢物,18到NASH,和15纤维化,共有27个。我们确定从F2到F3纤维化的进展与疾病自然史中的关键病理生理转变点一致。n=73的代谢物改变。
UNASSIGNED:循环代谢物的分析为NAFLD进展过程中的代谢变化提供了重要的见解,揭示NAFLD光谱中的代谢特征和NAFL特有的特征,NASH,和纤维化。F2-F3转变标志着NAFLD发病机制的关键代谢转变点,数据指出了代谢应激,特别是氧化应激的病理生理重要性。
UNASSIGNED:该研究已在Clinicaltrials.gov(NCT04442334)注册。
未经评估:非酒精性脂肪性肝病的特征是肝脏中脂肪的积聚,进展为肝功能障碍,疤痕,和不可逆转的肝功能衰竭,并且在全球范围内患病率显着增加。这里,我们测量了血液中的脂质和其他小分子(代谢物),目的是提供脂肪积聚的全面分子概述,肝纤维化,和诊断的严重性。我们确定了肝脏损伤进展的关键代谢分水岭,将严重疾病与轻度疾病分开,并显示特定的脂质和代谢物谱可以帮助区分和/或定义这些病例。
UNASSIGNED: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease with potentially severe complications including cirrhosis and hepatocellular carcinoma. Previously, we have identified circulating lipid signatures associating with liver fat content and non-alcoholic steatohepatitis (NASH). Here, we develop a metabolomic map across the NAFLD spectrum, defining interconnected metabolic signatures of steatosis (non-alcoholic fatty liver, NASH, and fibrosis).
UNASSIGNED: We performed mass spectrometry analysis of molecular lipids and polar metabolites in serum samples from the European NAFLD Registry patients (n = 627), representing the full spectrum of NAFLD. Using various univariate, multivariate, and machine learning statistical approaches, we interrogated metabolites across 3 clinical perspectives: steatosis, NASH, and fibrosis.
UNASSIGNED: Following generation of the NAFLD metabolic network, we identify 15 metabolites unique to steatosis, 18 to NASH, and 15 to fibrosis, with 27 common to all. We identified that progression from F2 to F3 fibrosis coincides with a key pathophysiological transition point in disease natural history, with n = 73 metabolites altered.
UNASSIGNED: Analysis of circulating metabolites provides important insights into the metabolic changes during NAFLD progression, revealing metabolic signatures across the NAFLD spectrum and features that are specific to NAFL, NASH, and fibrosis. The F2-F3 transition marks a critical metabolic transition point in NAFLD pathogenesis, with the data pointing to the pathophysiological importance of metabolic stress and specifically oxidative stress.
UNASSIGNED: The study is registered at Clinicaltrials.gov (NCT04442334).
UNASSIGNED: Non-alcoholic fatty liver disease is characterised by the build-up of fat in the liver, which progresses to liver dysfunction, scarring, and irreversible liver failure, and is markedly increasing in its prevalence worldwide. Here, we measured lipids and other small molecules (metabolites) in the blood with the aim of providing a comprehensive molecular overview of fat build-up, liver fibrosis, and diagnosed severity. We identify a key metabolic \'watershed\' in the progression of liver damage, separating severe disease from mild, and show that specific lipid and metabolite profiles can help distinguish and/or define these cases.