Short-Term Risk Stratification in Alcohol-Associated Hepatitis: Small HDL Particles and Inflammation Vulnerability...

Alcohol-associated hepatitis (AH) has high short-term mortality, whereas current prognostic models mainly reflect liver and renal dysfunction. The Metabolic Vulnerability Index (MVX) is a nuclear magnetic resonance-derived score comprising the Inflammation Vulnerability Index (IVX; small high-density lipoprotein particles [S-HDL-P] and GlycA) and the Metabolic Malnutrition Index (MMX). We evaluated whether MVX, IVX, and IVX components improve 90-day mortality prediction beyond Model for End-Stage Liver Disease (MELD) in AH.

Serum samples from 196 patients with AH, 169 heavy-drinking controls, and 351 healthy controls were analyzed by nuclear magnetic resonance spectroscopy. The primary outcome was 90-day AH-related mortality. Biomarkers were modeled continuously after standardization within the AH cohort; S-HDL-P was modeled per 1 SD decrease. Cox models were adjusted for MELD, age, sex, white blood cell count, and baseline antibiotic or corticosteroid use. Model performance was assessed using Akaike information criterion (AIC), likelihood-ratio testing, and Harrell's C-statistic.

Among patients with AH, 30 AH-related deaths occurred within 90 days (15.3%). IVX and MVX were highest in AH cases and increased with AH severity, whereas MMX did not consistently differentiate severity. Lower S-HDL-P was independently associated with 90-day mortality in fully adjusted models (HR, 1.84; 95% CI, 1.01-3.35; p = 0.045), whereas GlycA was not (HR, 0.86; 95% CI, 0.54-1.37; p = 0.527). Adding S-HDL-P improved fully adjusted MELD-based model fit (AIC, 298.97 vs. 301.46; LR p = 0.034; C-statistic, 0.741 vs. 0.729). IVX showed supportive improvement in model fit and discrimination (AIC, 299.81; LR p = 0.056; C-statistic, 0.749). Continuous MELD interaction analyses supported risk separation for S-HDL-P (LR χ² = 6.20; p = 0.045) and IVX (LR χ² = 6.64; p = 0.036).

Lower S-HDL-P appears to be the principal short-term prognostic component within the IVX domain in AH. S-HDL-P and IVX may refine MELD-based 90-day risk stratification, pending external validation.