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Diagnosis and follow\u2010up rely on invasive liver biopsy so blood\u2010based markers are urgently required.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate whether values of circulating metabolites from energy and one\u2010carbon (1\u2010C) metabolism may: (a) reflect hepatic mitochondrial flexibility failure and (b) act as NASH biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with severe obesity undergoing bariatric surgery (n\u00a0=\u00a0270) were investigated using quantitative targeted plasma metabolomics. Comparisons were with non\u2010obese controls without liver disease (n\u00a0=\u00a050). Obese patients with NASH (n\u00a0=\u00a053) and without NASH (n\u00a0=\u00a0130) representing extreme groups of liver disease were assessed to test the diagnostic ability of the measured circulating metabolites. Paired liver biopsy and plasma samples from NASH patients were available 1\u00a0year post\u2010surgery and were evaluated to monitor metabolomic changes with liver damage resolution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified correlations between human liver metabolism and obesity. High\u2010plasma \u03b1\u2010ketoglutarate (\u03b1\u2010KG) and lactate concentrations in NASH patients indicating citric acid cycle replenishment via glutaminolysis might also be a crucial point in NASH onset. Plasma measurements of \u03b1\u2010KG, \u03b2\u2010hydroxybutyrate, pyruvate and oxaloacetate reduced the uncertainty in clinical diagnosis of NASH [area under receiver operating characteristic curve (AUC) of 0.826] and predicted NASH resolution without ambiguity (AUC of 0.999).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Changes in plasma mitochondrial metabolites appear to be associated with NASH. These metabolic responses may be dynamically remodelled following resolution of liver damage through massive weight loss.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15606","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T16:15:22Z","timestamp":1576080922000},"page":"374-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Plasma metabolic alterations in patients with severe obesity and non\u2010alcoholic steatohepatitis"],"prefix":"10.1111","volume":"51","author":[{"given":"Noem\u00ed","family":"Cabr\u00e9","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery Universitat Rovira i Virgili Reus Spain"},{"name":"Unitat de Recerca Biom\u00e8dica (URB\u2010CRB) Hospital Universitari de Sant Joan Institut d\u2019Investigacio Sanitaria Pere Virgili Universitat Rovira i Virgili Reus 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