[Cardiometabolic and genetic factors in the progression of metabolic dysfunction-associated steatotic liver disease]

To evaluate the contribution of cardiometabolicfactors and PNPLA3 I148M (rs738409 C>G) gene polymorphism to the development of compensated advanced chronic liver disease (cACLD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

108 patients with MASLD were enrolled and formed the internal validation group; 30 patients with MASLD were selected for external validation. Anamnestic data, anthropometric and laboratory parameters and the presence of PNPLA3 gene polymorphism I148M (rs738409 C>G) were assessed. Steatosis was detected by assessing the controlled attenuation parameter. Liver elasticity was assessed by transient elastography. cACLD was detected when the liver stiffness was ≥8 kPa.

Statistically significant difference was observed in the internal validation group during comparison of the incidence of cACLD depending on the presence of arterial hypertension (odds ratio - OR 5.58; 95% confidence interval - CI 1.21-25.71), type 2 diabetes mellitus - T2DM (OR 4.58; 95% CI 1.59-13.21), obesity (OR 3.13; 95% CI 1.1-8.9), dyslipidemia (OR 6.12; 95% CI 1.33-28.19) and the mutant G allele of the PNPLA3 gene (OR 3.9; 95% CI 1.28-11.88). Patients with cACLD had significantly higher mean values of waist circumference (WC), alanine aminotransaminase, aspartate aminotransaminase, gamma-glutamyl transferase and triglycerides, non-invasive markers of steatosis and fibrosis. The compiled prognostic model demonstrated a direct relationship between the likelihood of developing cACLD and the presence of T2DM (adjusted odds ratio - AOR 3.28; 95% CI 0.62-17.33), dyslipidemia (AOR 5.89; 95% CI 1.21-28.67) and WC value (AOR 1.05; 95% CI 1.01-1.11). PNPLA3 I148M gene polymorphism did not significantly affect the development of late stages of the disease. External validation of the model showed its moderate diagnostic ability.

T2DM, dyslipidemia and WC values are the determining factors in the development of cACLD in patients with MASLD. The PNPLA3 I148M gene polymorphism has no leading importance for the development of the progressive course of MASLD in the studied cohort.