Hyperhomocysteinemia is linked to MASLD.

Background and aims: Homocysteine (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.

Methods: A 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.

Results: Hyperhomocysteinemia (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).

Conclusions: Our 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.