• Carlo De Matteis, Lucilla Crudele, Ersilia Di Buduo, Salvatore Cantatore, Raffaella Maria Gadaleta, Marica Cariello, Patrizia Suppressa, Gianfranco Antonica, Elsa Berardi, Giusi Graziano, and Antonio Moschetta.
• Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124 Bari, Italy.
• Eur. J. Intern. Med. 2025 Jan 1; 131: 495749-57.

Background And AimsHomocysteine (Hcy) levels are elevated in different conditions, including cardiovascular diseases (CVD), diabetes, and metabolic-associated steatotic liver disease (MASLD). In this observational retrospective study, we analyzed Hcy levels in a population of 901 outpatients, considering its putative etiological role in MASLD.MethodsA total of 901 outpatients underwent physical and biochemical evaluations. Abdominal and carotid ultrasound were performed to assess liver steatosis, carotid intima-media thickness (IMT) and presence of atherosclerotic plaque.ResultsHyperhomocysteinemia (HHcy) was identified in 140 subjects (16 %). Patients with HHcy showed glucose metabolism impairment (p < 0.001), altered lipid profile (p < 0.001), low Vitamin D levels (p < 0.0001), increased cardiovascular risk (p < 0.001). We then investigated the relationship between Hcy and MASLD (OR=3.6, p < 0.0001), finding that the relationship remained significant also when accounting for confounding variables (age, sex) (OR=3.2, p < 0.0001). Hcy values were significantly higher (p < 0.0001) in patients with MASLD (n = 78, 29.4 ± 10.1μmol/l) compared to those without MASLD (20.4 ± 4.8 1μmol/l). Furthermore, in MASLD patients we found a direct correlation between Hcy level and waist circumference (r = 0.3, p < 0.001) and an inverse correlation with both HDL-c (r=-0.4, p < 0.001) and Vitamin D levels (r=-0.24, p < 0.05).ConclusionsOur data suggest an intriguing scenario whereby HHcy is present in patients with MASLD and is associated to lower vitamin D and altered glucose and lipid profile. Thus, considering Hcy levels may help clinicians with the management of patients with increased MASLD risk.Copyright © 2024. Published by Elsevier B.V.

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