The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 3, 750–761 doi:10.1210/clinem/dgaa892 Clinical Research Article ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA 750 https://academic.oup.com/jcem © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Clinical Research Article Insulin Resistance Is Central to Long- Term Reversal of Histologic Nonalcoholic Steatohepatitis After Metabolic Surgery Maria Francesca Russo, 1,2, * Erminia Lembo, 1,2, * Andrea Mari, 3 Giulia Angelini, 1,2 Ornella Verrastro, 1,2 Giuseppe Nanni, 1,2 Maurizio Pompili, 1,2 Marco Raffaelli, 1,2 Fabio Maria Vecchio, 1,2 Stefan R. Bornstein, 4,5 and Geltrude Mingrone 1,2,4 1 Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; 2 Università Cattolica del Sacro Cuore Rome, 00168 Rome, Italy; 3 Institute of Neuroscience, National Research Council, 35127 Padua, Italy; 4 Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, SE1 9NH London, UK; and 5 Department of Medicine III, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, 01307 Dresden, Germany ORCiD number: 0000-0003-2021-528X (G. Mingrone). *M.F.R. and E.L. contributed equally to this work. Abbreviations: γ-GT, γ-glutamyltransferase; ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelets ratio; AST, aspartate aminotransferase; AUC, area under the curve; BPD, biliopancreatic diversion; C-peptide, connecting peptide; FIB4, Fibrosis-4 score; HDL, high-density lipoprotein; HOMA-IR, Homeostasis Model Assessment of Insulin Resistance; ISR, insulin secretion rate; LDL, low-density lipoprotein; NAFLD, nonalcoholic fatty liver disease; NAS, nonalcoholic fatty liver disease activity score; NASH, nonalcoholic steatohepatitis; NFS, nonalcoholic fatty liver disease fbrosis score; OGTT, oral glucose tolerance test; PLS-DA, partial least squares–discriminant analysis; RCT, randomized clinical trial; ROC, receiver operating characteristic curve; SAF, steatosis-activity-fbrosis; T2DM, type 2 diabetes mellitus; VIP, variable importance in the projection. Received: 1 September 2020; Editorial Decision: 22 November 2020; First Published Online: 28 November 2020; Corrected and Typeset: 16 January 2021. Abstract  Context: Nonalcoholic steatohepatitis (NASH) is considered the hepatic counterpart of metabolic syndrome. Objective: This work aimed to investigate the determinants of NASH reversal in patients undergoing biliopancreatic diversion (BPD) in a 5-year follow-up study. Methods: This prospective study was conducted at Policlinico Universitario Agostino Gemelli. A total of 37 patients underwent fne-needle liver biopsy during BPD. Ultrasonography-guided percutaneous liver biopsy was obtained 5 years after the operation. The primary outcome of our study was histologic NASH reversal at 5-year follow-up. To better characterize the clinical variables involved in the resolution of NASH, Downloaded from https://academic.oup.com/jcem/article/106/3/750/6009066 by guest on 01 July 2022