Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis

作者：Giulia Angelini, Simona Panunzi, Lidia Castagneto‐Gissey, Francesca Pellicanò, Andrea De Gaetano, Maurizio Pompili, Laura Riccardi, Matteo Garcovich, Marco Raffaelli, Luigi Ciccoritti, Ornella Verrastro, Maria Francesca Russo, Fabio Maria Vecchio, Giovanni Casella, James R. Casella-Mariolo, Luigi Papa, Pier Luigi Marini, Francesco Rubino, Carel Wynand le Roux, Stefan Richard Bornstein, Geltrude Mingrone · 发表于：Gut · 年份：2022 · DOI：10.1136/gutjnl-2022-327498 · 被引用次数：57 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolomics and Mass Spectrometry Studies、Liver physiology and pathology

Objective Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. Design This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14 + CD16 − monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis. Results The algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively. The area under the receiver operating characteristic (AUROC) for NA...