Academic Journal
The metabolic vulnerability index predicts outcomes in patients with metabolic dysfunction associated steatotic liver disease.
| Τίτλος: | The metabolic vulnerability index predicts outcomes in patients with metabolic dysfunction associated steatotic liver disease. |
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| Συγγραφείς: | Siddiqui MS; Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Van Natta ML; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Connelly MA; Labcorp, Morrisville, NC, USA., Clark J; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Neuschwander-Tetri BA; Saint Louis University, St. Louis, MO, USA., Diehl AM; Duke University, Durham, NC, USA., Dasarathy S; Cleveland Clinic, Cleveland, OH, USA., Loomba R; University of California San Diego School of Medicine, San Diego, CA, USA., Chalasani N; Indiana University School of Medicine, Indianapolis, IN, USA., Kowdley KV; Liver Institute Northwest, Seattle, WA, USA., Hameed B; University of California San Francisco School of Medicine, San Francisco, CA, USA., Wilson LA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Yates KP; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Belt P; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Kleiner DE; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Behling C; University of California San Diego School of Medicine, San Diego, CA, USA., Tonascia J; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Sanyal AJ; Virginia Commonwealth University School of Medicine, Richmond, VA, USA. arun.sanyal@vcuhealth.org. |
| Πηγή: | Nature communications [Nat Commun] 2026 Jun 23; Vol. 17 (1). Date of Electronic Publication: 2026 Jun 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| Ιατρικοί όροι (MeSH): | Non-alcoholic Fatty Liver Disease*/diagnosis , Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/mortality, End Stage Liver Disease/metabolism ; End Stage Liver Disease/mortality ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/mortality ; Liver Neoplasms/metabolism ; Liver Neoplasms/mortality ; Liver/metabolism ; Biomarkers/metabolism ; Humans ; Severity of Illness Index ; Male ; Female ; Adult ; Middle Aged ; Aged ; Prognosis |
| Περίληψη: | We evaluated the prognostic performance of the metabolic vulnerability index (MVX), reflective of inflammation and amino acid dysmetabolism, in a cohort (n = 1613) with the full histological spectrum of MASLD. Over a median follow up of 4 years, MVX predicts all-cause mortality (H.R. 2.7 (95% CI = 2.1-3.5) for every 10-point increment; p < 0.001), liver-related mortality (H.R. 5.1 (95% CI = 2.8-9.1); p < 0.001), hepatic decompensation (H.R. 2.5 (95% CI = 1.8-3.4); p < 0.001), a rise in model for end-stage liver disease (MELD) score to ≥ 15 (H.R. 1.8 (1.4-2.2); p < 0.001) and a decline in eGFR ≥ 40% (H.R. 1.5 (95% CI = 1.2-1.8); p < 0.001). A combination of fibrosis stage and MVX is superior to fibrosis stage alone for prediction of all-cause mortality (AUROC 0.79 vs 0.72, p = 0.01), liver-related mortality (0.95 vs 0.84, p = 0.002) hepatic decompensation (0.88 vs 0.86, p = 0.01) and hepatocellular cancer (0.84 vs 0.78, p = 0.001). These data support further development of MVX as a prognostic biomarker in MASLD. (© 2026. The Author(s).) |
| Competing Interests: | Competing interests: Dr. Behling is a salaried employee for Pacific Rim Pathology Lab. Dr. Behling’s institution (Pacific Rim Pathology Laboratory/Analytic Pathology Medical Group) currently receives support for biopsy related work through non-exclusive laboratory services and/or consulting agreements with: Akero Therapeutics Inc, Genesis Imaging Service, ICON, Imaging Health Care Specialists, Imperial Valley Family Medical Care Group, Mayo Laboratories, Medical Research Group Inc., MedPace, Roche-Ventana, Sharp Community Medical Group, Sharp Reese Stealy Medical Group, Sharp Healthcare, Southern California Research Center, and Takeda. Dr. Chalasani: For full disclosure, Dr. Chalasani has ongoing consulting activities (or had in preceding 12 months) with Madrigal, Zydus, Pfizer, Merck, Ventyx, GSK, and Altimmune. These consulting activities are generally in the areas of nonalcoholic fatty liver disease and drug hepatotoxicity. Dr. Chalasani receives research grant support from Exact Sciences and DSM, where his institution receives the funding. He has equity ownership in Avant Sante Therapeutics, LLC, a contract research organization. Dr. Clark has served on a scientific advisory board for Boehringer Ingelheim in the past 12 months. Dr. Connelly is an employee of Labcorp, Inc. Dr. Diehl has been a consultant for Allergan, Alderya Therapeutics, Aria Pharmaceutics, Casma, Filcitrine, Generon, Gilead, Glympse Bio, Merck, Novartis, Pfizer, RAPT Therapeutics, and SunBio Pharmaceuticals. In addition, her institution receives research grants from Allergan, Astra Zeneca, Boehringer Ingelheim, Celgene, Enyo, Excella Health, Galmed Pharmaceuticals, Gilead, Glympse Bio, Hanmi, Intercept, Inventiva, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Novartis, and Poxel. Dr. Hameed: His institution has received grant support from Gilead, Intercept, Pliant Therapeutics, Novo Nordisk, Madrigal, Salix. Dr. Hameed serves as a consultant or advisory board member for Mallinckrodt, Pleiogenix, CLDF, Pioneering Medicine VII, Inc Consultant. Stock options Pleiogenix. Dr. Kowdley declares research support from CymaBay Therapeutics; grants and/or contracts from 89Bio, Genfit, Gilead, GlaxoSmithKline, Hanmi, HighTide, Intercept, Madrigal, Mirum, NGM, Pfizer, Pliant, and Viking; royalties/licenses from UpToDate; consulting fees from 89Bio, Calliditas Therapeutics, CymaBay Therapeutics, Genfit, Gilead, Inipharm, Intercept, Madrigal, Mirum, NGM, and Pliant; payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Gilead, and Intercept; payment for expert testimony from the Department of Justice; participation in a Data Safety Monitoring Board or advisory board for CTI, Durect, and Labcorp; stock or stock options for Inipharm; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Sonic Insight. Dr. Loomba serves as a consultant or advisory board member for 89bio, Alnylam, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol-Myer Squibb, Cirius, CohBar, DiCerna, Galmed, Gilead, Glympse Bio, Intercept, Ionis, Metacrine, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sagimet, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, BristolMyers Squibb, Eli Lilly and Company, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Pfizer, pH Pharma, and Siemens. He is also co-founder of Liponexus, Inc. Dr. Neuschwander-Tetri: Advisor or consultant: Akero, Arrowhead, Corcept, GSK, Hepion, HistoIndex, Madrigal, Merck, Mirum, Sagimet, Senseion. Stock options: HepGene, HeptaBio. Institutional research grants: Madrigal. Dr. Sanyal: Stock options in Tiziana, Rivus, Durect, Northsea, Inversago. Consultant to Intercept, Gilead, Boehringer Ingelhiem, Astra Zeneca, Glaxo-Smith-Kline, Madrigal, Akero, Boston Pharma, Inventiva, Avant Sante, Merck, Pfizer, Eli Lilly, Novo Nordisk, Alnylam, Regeneron, Genentech, Amgen, Janssen, Glaxo Smith Kline, Sagimet, Zydus, Tern, Surrozen, Poxel, Myovant, Corcept, 89Bio, Pliant, Path AI, Histoindex, Chemomab, Takeda, Salix, Malinckrodt, Abbvie. Royalties from Elsevier, UptoDate. Dr. Siddiqui: AMRA advisory board; Institutional research grants: NovoNordisk. Ms. Belt, Dr. Dasarathy, Dr. Kleiner, Dr. Tonascia, Mr. Van Natta, Ms. Wilson, Ms. Yates: declare no conflicts of interest. |
| References: | Rinella, M.E. et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77, 1797–1835 (2023). Sanyal, A. J. et al. Non-invasive biomarkers of nonalcoholic steatohepatitis: the FNIH NIMBLE project. Nat. Med. 28, 430–432 (2022). (PMID: 10.1038/s41591-021-01652-8351453089588405) Dulai, P. S. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65, 1557–1565 (2017). (PMID: 10.1002/hep.29085281307885397356) Sanyal, A. J. et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N. Engl. J. Med. 385, 1559–1569 (2021). (PMID: 10.1056/NEJMoa2029349346700438881985) Shah, A. G. et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 7, 1104–1112 (2009). (PMID: 10.1016/j.cgh.2009.05.033195235353079239) Cusi, K. et al. Metabolic dysfunction-associated steatotic liver disease (MASLD) in people with diabetes: the need for screening and early intervention. A consensus report of the american diabetes association. Diabetes Care 48, 1057–1082 (2025). McPherson, S. et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am. J. Gastroenterol. 112, 740–751 (2017). (PMID: 10.1038/ajg.2016.45327725647) Boursier, J. et al. Impact of type 2 diabetes on the accuracy of noninvasive tests of liver fibrosis with resulting clinical implications. Clin. Gastroenterol. Hepatol. 21, 1243–1251.e1212 (2023). (PMID: 10.1016/j.cgh.2022.02.05935288342) Angulo, P. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–397.e310 (2015). (PMID: 10.1053/j.gastro.2015.04.043259356334516664) Ekstedt, M., Franzen, L. E., Mathiesen, U. L. & Kechagias, S. Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression. Scand. J. Gastroenterol. 47, 108–115 (2012). (PMID: 10.3109/00365521.2011.63402422126450) Kleiner, D. E. et al. Association of histologic disease activity with progression of nonalcoholic fatty liver disease. JAMA Netw. Open 2, e1912565 (2019). (PMID: 10.1001/jamanetworkopen.2019.12565315846816784786) Siddiqui, M. S. et al. Severity of nonalcoholic fatty liver disease and progression to cirrhosis are associated with atherogenic lipoprotein profile. Clin. Gastroenterol. Hepatol. 13, 1000–1008.e1003 (2015). (PMID: 10.1016/j.cgh.2014.10.00825311381) Powell, E. E. et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11, 74–80 (1990). (PMID: 10.1002/hep.18401101142295475) FDA. Biomarker Qualification: Evidentiary Framework Guidance for Industry and FDA Staff (Draft Guidance). (ed. Food and Drug Administration) (US Federal Govt., Maryland, 2018). FDA. Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment Guidance for Industry (US Food and Drug Administration, 2018). Sanyal, A.J. et al. Validation of a clinical risk-based classification system in a large nonalcoholic fatty liver disease real-world cohort. Clin. Gastroenterol. Hepatol 21, 2889–2900.e10 (2023). Anstee, Q. M. et al. Prognostic utility of Fibrosis-4 Index for risk of subsequent liver and cardiovascular events, and all-cause mortality in individuals with obesity and/or type 2 diabetes: a longitudinal cohort study. Lancet Reg. Health Eur. 36, 100780 (2024). (PMID: 10.1016/j.lanepe.2023.10078038188279) Kleiner, D. E. & Bedossa, P. Liver histology and clinical trials for nonalcoholic steatohepatitis-perspectives from 2 pathologists. Gastroenterology 149, 1305–1308 (2015). (PMID: 10.1053/j.gastro.2015.09.01526409177) Kleiner, D. E. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41, 1313–1321 (2005). (PMID: 10.1002/hep.2070115915461) |
| Grant Information: | U01DK061713 United States DK NIDDK NIH HHS; U01DK061718 United States DK NIDDK NIH HHS; U01DK061728 United States DK NIDDK NIH HHS; U01DK061731 United States DK NIDDK NIH HHS; U01DK061732 United States DK NIDDK NIH HHS; U01DK061734 United States DK NIDDK NIH HHS; U01DK061737 United States DK NIDDK NIH HHS; U01DK061738 United States DK NIDDK NIH HHS; U01DK061730 United States DK NIDDK NIH HHS; U24DK061730 United States DK NIDDK NIH HHS |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260623 Date Completed: 20260625 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13291223 |
| DOI: | 10.1038/s41467-026-73742-5 |
| PMID: | 42337268 |
| Βάση Δεδομένων: | MEDLINE |
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