EYES2022 ESE Young Endocrinologists and Scientists (EYES) 2022 Adrenal and Cardiovascular (12 abstracts)
Steroidomic approach for the characterization of patients with non-alcoholic fatty liver disease
Parasiliti-Caprino M 1 , Rosso C 2 , Ponzetto F 1 , Caviglia G. P 2 , Lopez C 1 , Armandi A 2 , Saracco G. M. 2 , Ghigo E 1 , Bugianesi E 2 & Maccario M 1
1University of Turin, Endocrinology, Diabetes and Metabolism; 2University of Turin, Unit of Gastroenterology
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 267 patients with biopsy-proven NAFLD and 112 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, according to the Kleiner score.
Results: Compared to CT, NAFLD patients were older (median age 51vs43, P < 0.001) and were characterized by a higher rate of MS (47%vs2%, P < 0.001). More than a half of steroids were deregulated in patients compared to CT. 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 0.83 with a sensitivity and specificity of 75% and 80%. No statistical differences were found between the accuracy of the multivariable model and the fibroscan (AUC 0.83) in the diagnosis of severe fibrosis, while the model combining clinical variable, significant steroids and fibroscan demonstrated a high accuracy for predicting severe fibrosis (AUC 0.90).
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.
Volume 83
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Endocrine Abstracts
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