Short‐Term Risk Stratification in Alcohol‐Associated Hepatitis: Small HDL Particles and Inflammation Vulnerability Index Values Improve Model for End‐Stage Liver Disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT Background 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. Methods 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. Results 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 χ 2 = 6.20; p = 0.045) and IVX (LR χ 2 = 6.64; p = 0.036). Conclusions 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.
DOI: 10.1111/acer.70388
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,110
Awards: Liquid biopsy for alcoholic hepatitis: diagnosis, prognosis and technology development, TREAT-VCU, Integrated Therapies for Alcohol use in Alcohol-associated Liver Disease (ITAALD) - Indiana University Data Coordinating Center, Integrated therapies for alcohol use and ALD (ITAALD) Network - IU Clinical Center, Translational Research and Evolving Alcoholic hepatitis Treatment (TREAT-ADMIN)
OpenAlex ID: W7202034981
