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Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease

Govaere Oivier; Orešič Matej; Bousier Jerome; Petta Salvatore; Geng Dawei; de Oliviera Claudia; Bugianesi Elisabetta; Daly Ann K; Schattenberg Jörn M; Anstee Quentin M; Hyötyläinen Tuulia; McGlinchey Aidan J; Ratziu Vlad; Allison Michael

Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease

Govaere Oivier
Orešič Matej
Bousier Jerome
Petta Salvatore
Geng Dawei
de Oliviera Claudia
Bugianesi Elisabetta
Daly Ann K
Schattenberg Jörn M
Anstee Quentin M
Hyötyläinen Tuulia
McGlinchey Aidan J
Ratziu Vlad
Allison Michael
Katso/Avaa
OresicEtAl2022MetabolicSignaturesAcross.pdf (2.426Mb)
Lataukset: 

Elsevier B.V.
doi:10.1016/j.jhepr.2022.100477
URI
https://doi.org/10.1016/j.jhepr.2022.100477
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022081154310
Tiivistelmä

Background & Aims

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).

Methods

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.

Results

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.

Conclusions

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.

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