ECE2022 Rapid Communications Rapid Communications 13: Adrenal and Cardiovascular Endocrinology 2 (8 abstracts)
Steroidomic approach for the characterization of patients with non-alcoholic fatty liver disease
Mirko Parasiliti Caprino 1 , Chiara Rosso 2 , Federico Ponzetto 1 , Gian Paolo Caviglia 2 , Chiara Lopez 1 , Angelo Armandi 2 , Giorgio Maria Saracco 2 , Ezio Ghigo 1 , Elisabetta Bugianesi 2 & Mauro Maccario 1
1University of Turin, Endocrinology, Diabetes and Metabolism, Turin, Italy; 2University of Turin, Unit of Gastroenterology, Turin, Italy
Introduction: The onset and progression of liver damage in non-alcoholic fatty liver disease (NAFLD) is tightly associated with metabolic derangements. Steroids may affect lipid metabolism but their alterations in the setting of NAFLD remain to be fully explored.
Patients and Methods: We analyzed data from 121 patients with biopsy-proven NAFLD and 108 controls (CT). A panel of 26 steroids (including glucocorticoids, mineralocorticoids, androgens, and progestogens as well as representative glucuro- and sulphoconjugated metabolites) were measured on plasma samples by liquid chromatography coupled to mass spectrometry (LC-MS/MS). Severe hepatic fibrosis was defined by F≥3.
Results: Compared to CT, NAFLD patients were older (median age 51 vs 43, P<0.001) and were characterized by a higher rate of MS (47% vs 2%, P<0.001). More than a half of steroids were deregulated in patients compared to CT. At liver histology, the prevalence of absent/mild, moderate, and severe fibrosis was 50.4%, 10.8% and 38.8%, respectively. Circulating levels of 16 compounds showed a significant stepwise decrease according to the degree of hepatic fibrosis. At univariate analysis, testosterone, and its derivatives, androsterone metabolites, etiocholanolone metabolites and glicoandrogens metabolites were differentially expressed in patients with severe fibrosis compared to those with absent/moderate fibrosis. After multivariable logistic regression analysis adjusted for age, gender and type 2 diabetes, epitestosterone sulphate, 5α-androstan-3α,17β-diol-3-glucuronide and androsterone sulphate levels were significantly associated with F≥3. The diagnostic accuracy of the model for the identification of F≥3 was 0.91 with a sensitivity and specificity of 87% and 85 %, respectively, and with a positive and negative predictive value of 78% and 91%, respectively.
Conclusions: In NAFLD patients, alterations in androgens and their glucuro- and sulphoconjugated metabolites levels could be expression of compromised 1) liver steroidogenesis or 2) liver steroid homeostasis regulation and are strongly associated with severe fibrosis. This research has been supported by the Italian MIUR under the programme “Dipartimenti di Eccellenza 2018-2022”, project code D15D18000410001.
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Endocrine Abstracts
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