O2- CHARACTERIZATION OF STEATOTIC LIVER DISEASE AND THE ROLE OF GENETIC BACKGROUND IN LATIN AMERICA

Abstract

Conflict of interest: Yes, FONDECYT #1241450 Introduction and Objectives: Although Latinos living in the United States are at higher risk of steatotic liver disease (SLD), information from Latin American countries is extremely scarce. We aimed to characterize SLD in Latin America and explore the role of the common genetic variants in this region. Patients / Materials and Methods: Cross-sectional multicenter study including individuals with SLD who undergo liver biopsy or transient elastography (TE) between 2003–2024. TE thresholds were established as follows: significant fibrosis (F2) ≥8.2 kPa, advanced fibrosis (F3) ≥9.7 kPa, and cirrhosis (F4) ≥13.6 kPa. Analyses included logistic binary regression. Results and Discussion: We included 2,159 patients (93.7% metabolic dysfunction-associated SLD and 6.3% alcohol-associated liver disease) from 13 centers in 5 countries (Argentina, Brazil, Chile, Mexico, and Peru). Mean age was 54.3±14.3 years old, 58.8% were female, and 60.2% had a liver biopsy. Around 18% had significant fibrosis, 18.7% advanced fibrosis, and 16.2% had cirrhosis. Additionally, 21.8% were homozygous carriers of the rs738409 risk polymorphism (PNPLA3 I148M variant), 42.5% were heterozygotes, and 35.7% were non-carriers. In an adjusted multivariable model, only age (odds ratio [OR]:1.03; 95%CI:1.01–1.04; p=0.030), body mass index (BMI) (OR:1.04; 95%CI:1.01–1.08, p=0.008), prediabetes/diabetes (OR:2.41; 95%CI:1.48–3.91, p<0.0001), and PNPLA3 risk allele carriers (heterozygotes: OR:2.86, 95%CI:1.78–4.61; p<0.0001, and homozygous: OR:25.37, 95%CI:4.30–149.54; p<0.001) were associated with a higher risk of advanced fibrosis. Similar results were observed in multivariable models to assess the risk of cirrhosis. Prevalence of advanced fibrosis or cirrhosis was higher in those with prediabetes/diabetes and homozygous carriers of the PNPLA3 I148M variant than those without both risk factors (48.6% vs. 27.9%, p<0.0001) (Figure). Conclusions: Age, BMI, prediabetes, diabetes, and carriers of the PNPLA3 risk allele carriers were the leading risk factors for advanced fibrosis in SLD. PNPLA3 I148M variant carriers are frequent in SLD patients in Latin America, and genotyping could be established to stratify the risk of liver fibrosis routinely in clinical practice. (Supported Fondecyt #1241450)