Title : Differentiating simple and aggressive phenotypes of metabolic dysfunction-associated steatotic liver disease utilizing bioelectrical impedance-derived metabolic age gap
Abstract:
Background: The clinical heterogeneity of metabolic dysfunction-associated steatotic liver disease (MASLD/MAFLD) necessitates precise phenotyping. Conventional markers like body mass index (BMI) fail to distinguish between benign fat accumulation and progressive tissue injury. This study aims to evaluate the utility of the bioelectrical impedance analysis (BIA)-derived metabolic age gap in differentiating simple (non-aggressive) from aggressive (progressive) hepatic steatosis phenotypes.
Methods: A monocentric, controlled trial included 20 practically healthy individuals and 31 patients with unexplained hepatomegaly. Comprehensive body composition assessment was performed via organ-tissue bioimpedancemetry (BIM). Subclinical liver fibrosis (F) and controlled attenuation parameter (CAP/S) were quantified using transient elastography (iLivtouch FT 100). Functional metabolic flexibility was evaluated through an L-lysine-induced ketosis breath test.
Results: Two distinct clinical phenotypes were identified based on the metabolic age (MET-age) vs. chronological age (CHR-age) discrepancy. A mild discrepancy (>1) but (<6 years) paired with maintained metabolic flexibility characterized the Simple Steatosis Phenotype, displaying low steatosis frequencies (1%–5%) and no advanced fibrosis. Conversely, the Aggressive Steatosis Phenotype was defined by severe age acceleration and metabolic rigidity. In healthy subjects, a MET-age advancement (>2) years strongly predicted underlying aggressive shifts (Severe Steatosis (S=3); significant correlation with fibrosis (r=0.6, p=0.01\); Odds Ratio (OR= 80.00). In hepatomegaly patients, a cutoff gap of age 6 years highly predicted the aggressive co-expression of severe steatosis and fibrosis (OR = 19.80); Sensitivity: (81.25%) accompanied by systemic and local dysmetabolism.
Conclusion: The metabolic-chronological age gap serves as a robust, non-invasive biomarker to differentiate simple hepatic steatosis from the aggressive, fibrogenic phenotype, far outperforming conventional anthropometric indices.
Keywords: Metabolic age; Bioelectrical impedance vector analysis (BIVA); Metabolic dysfunction-associated steatotic liver disease (MASLD); Hepatic steatosis phenotype; Liver fibrosis; Transient elastography; Metabolic flexibility; Hepatomegaly.
