Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study

There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0-F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.

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Journal
Nature Medicine
Published
2026-07-24
DOI
https://doi.org/10.1038/s41591-026-04496-2
Primary Topic
Liver Disease Diagnosis and Treatment
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article
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article

Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study

Michael Pavlides, Yasaman Vali, José M. MATO, Jérémy Magnanensi et al.
Nature Medicine
Liver Disease Diagnosis and Treatment
article

Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study

Michael Pavlides, Yasaman Vali, José M. MATO, Jérémy Magnanensi, Elizabeth Shumbayawonda, J H Van der Lee, Mathilde Wagner, Fiona Oakley, Paolo Missier, Miljen Martić, Rambabu Surabattula, Hannele Yki‐Järvinen, Sergio Rodrigues-Cuenca, Olivier Govaere, Toni Vidal-Puig, Mattias Ekstedt, Manuel Romero‐Gómez, Clifford A. Brass, Ferenc E. Mózes, Pierre Bédossa, Karine Clément, Elisabetta Bugianesi, Maurice Michel, Max Nieuwdorp, Simon Cockell, Mark Campbell, Diana Julie Leeming, Ann Daly, M Schneider, Óscar Millet, Rajarshi Banerjee, Jérôme Boursier, Rafael Patiño‐Navarrete, Michael Kalutkiewicz, Kristy Wonders, Salvatore Petta, Paul Hockings, Vlad Ratziu, Salma Akhtar, Stefan Neubauer, Harrison SA, Richard L. Ehman, Matej Orešič, Guruprasad Padur Aithal, Athanasios Angelakis, Jörn M. Schattenberg, Seliat Olodo-Atitebi, Matthew McTeer, Carla Yunis, Isabel Fernández-Lizaranzu, Adrian Huber, Jean‐François Dufour, Detlef Schuppan, Emrich Tilman, Matt Breckons, Chris Lelliott, S. Davies, B Straub, Michael E.D. Allison, Patrick M. Bossuyt, Heather J. Cordell, Céline Fournier-Poizat, Yaïr Acherman, Kay Pepin, Aidan McGlinchey, Arnold van de Laar, E Godfrey, J Schattenberg, R Pais, Juan M. Pericàs, Quentin M. Anstee, Evangelia Petsalaki, Ferenc E. Mózes, Rocio Aller, Theresa Tuthill, Sudha Myneni, Adriaan G. Holleboom, Jeremy F. Cobbold, Naomi F. Lange, Luke Vale, Christopher P. Day, Tuulia Hyötyläinen, Michele Vacca, Valerie Paradis, Yemi Oliboyede, Morten Karsdal, Dina Tiniakos, Ioannis Kamzolas, Annalisa Berzigotti
article en

Abstract

There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0-F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.

Nature Medicine
Linköping University (SE), Universidad de Valladolid (ES), University of Bern (CH), Novartis (Switzerland) (CH), Boehringer Ingelheim (Germany) (DE), Nottingham University Hospitals NHS Trust (GB), University of Helsinki (FI), University of Nottingham (GB), Inserm (FR), Pfizer (United States) (US), Johannes Gutenberg University Mainz (DE), National and Kapodistrian University of Athens (GR), Örebro University (SE), Hôpital Beaujon (FR), Helsinki University Hospital (FI), University Hospital of Bern (CH), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Cambridge University Hospitals NHS Foundation Trust (GB), Centre for Life (GB), Foundation for Liver Research (GB), Sorbonne Université (FR), University of Oxford (GB), University Medical Center of the Johannes Gutenberg University Mainz (DE), Nutrition et obésité : approches systémiques (FR), Assistance Publique – Hôpitaux de Paris (FR), Spaarne Ziekenhuis (NL), Minerva Foundation (FI), Vall d'Hebron Institut de Recerca (ES), Genfit (France) (FR), CIC bioGUNE (ES), Centro de Investigación Biomédica en Red (ES), Antaros Medical (Sweden) (SE), Resolve Therapeutics (United States) (US), Wellcome/MRC Institute of Metabolic Science (GB), University of Minnesota Rochester (US), NIHR Nottingham Digestive Diseases Biomedical Research Unit (GB), Pitié-Salpêtrière Hospital (FR), Mayo Clinic in Arizona (US), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES), Instituto de Biomedicina de Sevilla (ES), NIHR Newcastle Biomedical Research Centre (GB), Nordic Bioscience (Denmark) (DK), Oxford BioMedica (United Kingdom) (GB), Nottingham Biomedical Research Centre (GB), Amsterdam University Medical Centers (NL), Hospital Universitario Virgen del Rocío (ES), Fondation pour l’innovation en Cadiométabolisme et Nutrition (FR), Medical Research Network (US), Novartis Institutes for BioMedical Research, Université d'Angers (FR), University of Turin (IT), University of Bari Aldo Moro (IT), Universidad de Sevilla (ES), Newcastle University (GB), University of Amsterdam (NL), Saarland University (DE)
Pfizer, Helsingin Yliopisto, Canadian Institute for Theoretical Astrophysics, Universidad de Sevilla, University of Bern, Nottingham University Hospitals NHS Trust, European Federation of Pharmaceutical Industries and Associations, Inselspital, Universitätsspital Bern, Amsterdam University Medical Centers, Cancer Research UK, National Institute for Health and Care Research, University of Cambridge, University of Oxford, Newcastle University, European Commission, University of Nottingham, Minerva Foundation, Universiteit van Amsterdam, Ministero dell’Istruzione, dell’Università e della Ricerca, Newcastle upon Tyne Hospitals NHS Foundation Trust, Linköpings Universitet, National and Kapodistrian University of Athens, Universität des Saarlandes, Oxford University Hospitals NHS Foundation Trust, Universidad de Valladolid, Fakultet Medicinskih Nauka, Univerziteta U Kragujevcu, Innovative Medicines Initiative, Universitat Autònoma de Barcelona, Siemens Healthineers, Novartis Institutes for BioMedical Research, HORIZON EUROPE Framework Programme, Faculty of Medical Sciences, Newcastle University, NIHR Newcastle Biomedical Research Centre, NIHR Oxford Biomedical Research Centre, NIHR Nottingham Biomedical Research Centre
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Openalex Percentile: Top 8%
Liver Disease Diagnosis and Treatment
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