Liver Transplantation and Metabolic Dysfunction Associated Steatotic Liver Disease Is Associated with Markers of Metabolic Risk and Inflammation

Dig Dis Sci. 2025 Jun;70(6):2147-2155. doi: 10.1007/s10620-025-09072-1. Epub 2025 Apr 24.

Abstract

Background: Liver transplant (LT) recipients are at high risk of cardiometabolic disease and mortality. However, routinely employed clinical risk tools have sub-optimal diagnostic performance due to transplant related biological changes. Metabolic vulnerability index (MVX) is a serum-based composite biomarker comprised of nutritional risk [metabolic malnutrition index or MMX] and chronic inflammation [inflammatory vulnerability index or IVX]. MVX is a predictor of cardiovascular risk and all-cause mortality in the general population, however, the effect of LT on MVX is unknown.

Methods: To better quantify MVX after transplantation, LT recipients (n = 181) prospectively enrolled in a natural history study were matched with non transplant controls from the MESA study of healthy individuals. All controls were matched 1:1 regarding age and gender. Additionally, lean controls were identified as those with BMI < 25 kg/m2 and BMI-matched controls who were propensity matched for BMI.

Results: Compared to matched controls, LT recipients had significantly higher MVX (56.9 ± 10.1 vs. 45.8 ± 9.4 vs. 44.8 ± 9.3, p < 0.001), IVX [53.1 ± 12 vs. 39.3 ± 11.2 vs. 40.2 ± 10.9, p < 0.001), and MMX (58.7 ± 8.2 vs. 55.4 ± 6.5 vs. 53.1 ± 6.0, p < 0.001). No significant differences were noted in MVX in LT recipients who developed metabolic dysfunction associated steatotic liver disease (MASLD) after LT. In a multivariate analysis, MVX scores were positively associated with female gender, diabetes, serum AST and BMI, and negatively with dyslipidemia.

Conclusion: LT is associated with a significant increase in MVX and its components, suggesting a heightened risk in LT recipients that is above that of the non-LT population. Future well designed prospective studies are required to calibrate MVX to clinical outcomes in LT patients.

Keywords: Frailty; Inflammation; Liver transplantation; Metabolic dysfunction associated steatohepatitis; Metabolic vulnerability index.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Fatty Liver* / blood
  • Female
  • Humans
  • Inflammation* / blood
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Assessment
  • Risk Factors

Substances

  • Biomarkers