[en] Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with obesity. Sexual dimorphism is present in MASLD. A noninvasive test to diagnose the severity of the disease, in particular the presence of Metabolic dysfunction-associated steatohepatitis (MASH), is lacking. This European multicenter prospective study uses a blood test based on mid-infrared (MIR) metabolic fingerprinting of individuals with severe or morbid obesity to diagnose MASH. Three hundred eighty-two individuals with severe or morbid obesity undergoing bariatric surgery were enrolled prospectively. Liver biopsies were obtained during surgery and assessed centrally. An algorithm was defined to calculate a score from the recorded MIR spectrum and to establish a diagnostic threshold to classify patients with MASH. Among the women (n = 217), MASH was diagnosed in 14.3% of cases. For women, the performance in terms of AUC were 0.83 and 0.82 in the calibration and validation groups, respectively. For a threshold of 0.1817, sensitivities were 86% and 70%, specificities were 81% and 75%, PPV were 43% and 32%, NPV were 97% and 94% and ACC were 82% and 74% for the calibration and validation groups, respectively. For men (n = 78; MASH: 33.3%), the performance of the spectral model was poor. The metabolic fingerprint obtained by MIR spectroscopy can rule out MASH in women with severe or morbid obesity. Its value in men needs new studies.Trial registration: ClinicalTrials.gov identifier: ClinicalTrials.gov identifier: NCT03978247 (04/06/2019).
Nguyen-Khac, Eric; Department of Gastroenterology, Amiens University Hospital, Picardie University, Amiens, France
Régimbeau, Jean-Marc; Department of Digestive Surgery, Amiens, France ; SSPC (Simplification des Soins des Patients Complexes) - UR7518, Unit of Clinical Research, University of Picardie Jules Verne, Amiens, France
Dharhri, Abdennaceur; Department of Digestive Surgery, Amiens, France ; SSPC (Simplification des Soins des Patients Complexes) - UR7518, Unit of Clinical Research, University of Picardie Jules Verne, Amiens, France
Chatelain, Denis; Department of Pathology, Amiens University and Hospital, Université de Picardie Jules Verne, Amiens, France
Khamphommala, Litavan; Department of Digestive, Hepatobiliary Surgery, Centre Hospitalier Privé Saint-Grégoire, Saint-Gregoire, France
Gautier, Anne-Lise; Biology Laboratory, Centre Hospitalier Privé Saint-Grégoire, Saint-Gregoire, France
Le Berre, Nathalie; Ouest Pathologie, Rennes, France
Frey, Sébastien; Digestive Surgery, University Hospital of Nice, Archet 2 Hospital, Nice, France
Bronowicki, Jean-Pierre; Inserm U1254 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
Brunaud, Laurent; Department of Gastrointestinal, Visceral, Metabolic, and Cancer Surgery (CVMC), Faculté de Medicine, CHRU NANCY, Hopital Brabois adultes, INSERM U1256-NGERE, Université de Lorraine, 54511, Vandoeuvre-les-Nancy, France
Maréchal, Chloé; Inserm U1254 and Department of Hepato-Gastroenterology, University Hospital of Nancy Brabois, Université de Lorraine, Vandoeuvre-les-Nancy, France
Blanchet, Marie-Cécile; Department of General, Visceral and Endocrine Surgery, Clinique de la Sauvegarde, Lyon, France
Frering, Vincent; Department of General, Visceral and Endocrine Surgery, Clinique de la Sauvegarde, Lyon, France
Delwaide, Jean ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive ; Université de Liège - ULiège > Département des sciences cliniques
KOHNEN, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
HAUMANN, Alexandre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Sarfati-Lebreton, Marine; Department of Hepato-Gastroenterology and Digestive Oncology, Université, Angers University Hospital, Angers, France
Tariel, Hugues; DIAFIR, Rennes, France
Bernard, Jérôme; DIAFIR, Rennes, France
Toullec, Alexis; DIAFIR, Rennes, France
Boursier, Jérôme; Department of Hepato-Gastroenterology and Digestive Oncology, Université, Angers University Hospital, Angers, France
Bedossa, Pierre; Department of Pathology, Beaujon Hospital Paris Diderot University, Paris, France
INSERM - Institut National de la Santé et de la Recherche Médicale UniCA - Université Côte d'Azur ANR - Agence Nationale de la Recherche
Funding text :
This work was supported by grants from INSERM (France) and was supported by the French government through the "Investments for the Future" LABEX SIGNALIFE (#ANR-11-LABX-0028–01) and the UCAJEDI Investments in the Future project managed by the National Research Agency (ANR) with the reference number #ANR-15-IDEX-01.
M.E. Rinella J.V. Lazarus V. Ratziu et al. A multi–society Delphi consensus statement on new fatty liver disease nomenclature J. Hepatol. 2023 10.1016/j.jhep.2023.06.003 38906627
K. Riazi H. Azhari J.H. Charette et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis Lancet Gastroenterol. Hepatol. 2022 7 9 851 861 10.1016/S2468-1253(22)00165-0 35798021
Z.M. Younossi A.B. Koenig D. Abdelatif Y. Fazel L. Henry M. Wymer Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes Hepatology 2016 64 1 73 10.1002/hep.28431 26707365
R. Divella A. Mazzocca A. Daniele C. Sabbà A. Paradiso Obesity, nonalcoholic fatty liver disease and adipocytokines network in promotion of cancer Int. J. Biol. Sci. 2019 15 3 610 616 10.7150/ijbs.29599 30745847 6367583
C.M. Hales M.D. Carroll C.D. Fryar C.L. Ogden Prevalence of obesity and severe obesity among adults: United States, 2017–2018 NCHS Data Brief. 2020 360 1 8
World Health Organization. Obesity and overweight. Accessed June 8, 2023. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
E.E. Powell V.W.S. Wong M. Rinella Non-alcoholic fatty liver disease Lancet 2021 397 10290 2212 2224 10.1016/S0140-6736(20)32511-3 33894145
R.J. Wong R. Cheung A. Ahmed Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the US Hepatology 2014 59 6 2188 2195 10.1002/hep.26986 24375711
J.I. Mechanick C. Apovian S. Brethauer et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures – 2019 update: cosponsored by american association of clinical endocrinologists/american college of endocrinology, the obesity society, american society for metabolic & bariatric surgery, obesity medicine association, and american society of anesthesiologists * Endocrine Pract. 2019 25 1 75 10.4158/GL-2019-0406
L. Castera M. Friedrich-Rust R. Loomba Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease Gastroenterology 2019 156 5 1264 1281.e4 10.1053/j.gastro.2018.12.036 30660725
A. Berzigotti E. Tsochatzis J. Boursier et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update J. Hepatol. 2021 75 3 659 689 10.1016/j.jhep.2021.05.025
I. Mikolasevic L. Orlic N. Franjic G. Hauser D. Stimac S. Milic Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J. Gastroenterol. 2016 22 32 7236 7251 10.3748/wjg.v22.i32.7236 27621571 4997649
J. Keirsse E. Lahaye A. Bouter et al. Mapping bacterial surface population physiology in real-time: infrared spectroscopy of proteus mirabilis swarm colonies Appl. Spectrosc. 2006 60 6 584 591 2006ApSpe.60.584K 10.1366/000370206777670558 16808858
M.L. Anne C.L. Lan V. Monbet et al. Fiber evanescent wave spectroscopy using the mid-infrared provides useful fingerprints for metabolic profiling in humans JBO 2009 14 5 2009JBO..14e4033A 10.1117/1.3253319 19895135
R. Anty M. Morvan M.L. Corvec et al. The mid-infrared spectroscopy: a novel non-invasive diagnostic tool for NASH diagnosis in severe obesity JHEPReport 2019 1 5 361 368 10.1016/j.jhepr.2019.09.005
K. Cusi S. Isaacs D. Barb et al. American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the american association for the study of liver diseases (AASLD) Endocrine Pract. 2022 28 5 528 562 10.1016/j.eprac.2022.03.010
D.A. Koutoukidis N.M. Astbury K.E. Tudor et al. Association of weight loss interventions with changes in biomarkers of nonalcoholic fatty liver disease: a systematic review and meta-analysis JAMA Internal Med. 2019 179 9 1262 1271 10.1001/jamainternmed.2019.2248
P.N. Newsome K. Buchholtz K. Cusi et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis N Engl. J. Med. 2021 384 12 1113 1124 10.1056/NEJMoa2028395 33185364
S.M. Francque P. Bedossa V. Ratziu et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH N Engl. J. Med. 2021 385 17 1547 1558 10.1056/NEJMoa2036205 34670042
R. Loomba A.J. Sanyal K.V. Kowdley et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH New England J. Med. 2023 10.1056/NEJMoa2304286
S.A. Harrison M.R. Bashir C.D. Guy et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial Lancet 2019 394 10213 2012 2024 10.1016/S0140-6736(19)32517-6 31727409
Karim G, Bansal MB. Resmetirom: An Orally Administered, Small-molecule, Liver-directed, β-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis. touchREVIEWS in Endocrinology. Published online May 2023. Accessed August 13, 2023. https://www.touchendocrinology.com/liver-disorders/journal-articles/resmetirom-an-orally-administered-small-molecule-liver-directed-%ce%b2-selective-thr-agonist-for-the-treatment-of-non-alcoholic-fatty-liver-disease-and-non-alcoholic-steatohepatitis/
D. Baldwin M. Chennakesavalu A. Gangemi Systematic review and meta-analysis of Roux-en-Y gastric bypass against laparoscopic sleeve gastrectomy for amelioration of NAFLD using four criteria Surg. Obesity Related Dis. 2019 15 12 2123 2130 10.1016/j.soard.2019.09.060
K. Hajifathalian A. Mehta B. Ang et al. Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty Gastrointestinal Endosc. 2021 93 5 1110 1118 10.1016/j.gie.2020.08.023
P. Jirapinyo T.R. McCarty R.D. Dolan R. Shah C.C. Thompson Effect of endoscopic bariatric and metabolic therapies on nonalcoholic fatty liver disease: a systematic review and meta-analysis Clin. Gastroenterol. Hepatol. 2022 20 3 511 524.e1 10.1016/j.cgh.2021.03.017 33727164
R. Anty A. Iannelli S. Patouraux et al. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients Alimentary Pharmacol. Therapeut. 2010 32 11–12 1315 1322 10.1111/j.1365-2036.2010.04480.x
V. Ajmera R. Loomba Imaging biomarkers of NAFLD, NASH, and fibrosis Mol. Metabol. 2021 50 10.1016/j.molmet.2021.101167
Mitchell BL, Yasui Y, Li CI, Fitzpatrick AL, Lampe PD. Impact of freeze-thaw cycles and storage time on plasma samples used in mass spectrometry based biomarker discovery projects. Cancer informatics. 2005;1. Accessed July 21, 2016. http://search.proquest.com/openview/c17cce59cda07976b30c99759f0740a6/1?pq-origsite=gscholar
M. Ishikawa K. Maekawa K. Saito et al. Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects’ gender and age. Scuteri A, ed PLoS ONE 2014 9 3 e91806 2014PLoSO..991806I 10.1371/journal.pone.0091806 24632803 3954792
L. Lovergne P. Bouzy V. Untereiner et al. Biofluid infrared spectro-diagnostics: pre-analytical considerations for clinical applications Faraday Discuss. Published online 2016 10.1039/C5FD00184F
A. Lonardo F. Nascimbeni S. Ballestri et al. Sex differences in NAFLD: state of the art and identification of research gaps Hepatology 2019 70 4 1457 1469 10.1002/hep.30626 30924946
M.T. Long A. Pedley J.M. Massaro et al. A simple clinical model predicts incident hepatic steatosis in a community-based cohort: The Framingham Heart Study Liver Int. 2018 38 8 1495 1503 10.1111/liv.13709 29377504 6206437
C. Lee J. Kim J. Han et al. Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis Nat. Commun. 2022 13 578 2022NatCo.13.578L 10.1038/s41467-022-28138-6 35102146 8803937
P.K. Jena L. Sheng H.X. Liu et al. Western diet-induced dysbiosis in farnesoid X receptor knockout mice causes persistent hepatic inflammation after antibiotic treatment Am. J. Pathol. 2017 187 8 1800 1813 10.1016/j.ajpath.2017.04.019 28711154 5530909
S.L. Klein I. Marriott E.N. Fish Sex-based differences in immune function and responses to vaccination Trans. Royal Soc. Trop. Med. Hygiene 2015 109 1 9 15 10.1093/trstmh/tru167
S. Smati A. Polizzi A. Fougerat et al. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target Gut 2022 71 4 807 821 10.1136/gutjnl-2020-323323 33903148
J. Vandel J. Dubois-Chevalier C. Gheeraert et al. Hepatic molecular signatures highlight the sexual dimorphism of nonalcoholic steatohepatitis (NASH) Hepatology 2021 73 3 920 936 10.1002/hep.31312 32394476
P. Mathurin F. Gonzalez O. Kerdraon et al. The evolution of severe steatosis after bariatric surgery is related to insulin resistance Gastroenterology 2006 130 6 1617 1624 10.1053/j.gastro.2006.02.024 16697725
P. Mathurin A. Hollebecque L. Arnalsteen et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease Gastroenterology 2009 137 2 532 540 10.1053/j.gastro.2009.04.052 19409898
P. Bedossa C. Poitou N. Veyrie et al. Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients Hepatology 2012 56 5 1751 1759 10.1002/hep.25889 22707395
E.M. Brunt C.G. Janney A.M. Di Bisceglie B.A. Neuschwander-Tetri B.R. Bacon Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions Am. J. Gastroenterol. 1999 94 9 2467 2474 10.1111/j.1572-0241.1999.01377.x 10484010
J.D. Albert M. Le Corvec O. Berthoud et al. Ruling out septic arthritis risk in a few minutes using mid-infrared spectroscopy in synovial fluids Rheumatology 2021 60 3 1158 1165 10.1093/rheumatology/keaa373 32885254
R Core Team; Ayman, S.; Mohamed, A.A.; Hassen, M. R: A Language and Environment for Statistical Computing 2021. Open J. Appl. Sci. 2021, 11, 6. Accessed August 13, 2023. https://www.gbif.org/tool/81287/r-a-language-and-environment-for-statistical-computing
