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

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. Predicting clinical outcomes in metabolic dysfunction–associated steatotic liver disease remains challenging using existing biomarkers. Here, the authors show that a metabolic vulnerability index predicts death and liver events and improves risk prediction beyond fibrosis alone.