The metabolic vulnerability index predicts outcomes in patients with metabolic dysfunction associated steatotic liver disease.

Siddiqui, Mohammad S; Van Natta, Mark L; Connelly, Margery A; Clark, Jeanne; Neuschwander-Tetri, Brent A; Diehl, Anna Mae; Dasarathy, Srinivasan; Loomba, Rohit et al. · Nat Commun · 2026

prospective_cohort · Level II

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Abstract

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.

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