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

Yes, FONDECYT #1241450 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. 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. 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). 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)

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Journal
Annals of Hepatology
Published
2024-12-01
DOI
https://doi.org/10.1016/j.aohep.2024.101597
Primary Topic
Liver Disease Diagnosis and Treatment
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article
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article

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

Carolina Aguilera, Mísia Joyner de Sousa Dias Monteiro, Francisco Barrera, Billy Dunn et al.
Annals of Hepatology
Liver Disease Diagnosis and Treatment
article

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

Carolina Aguilera, Mísia Joyner de Sousa Dias Monteiro, Francisco Barrera, Billy Dunn, Rohit S. Loomba, Adelina Lozano, Graciela Castro‐Narro, Adrian Carlos Gadano, Nathalie Carvalho Leite, Fernando Javier Barreyro, Manuel Mendizábal, Margarita Pizarro, Francisco Javier Idalsoaga, Mário Guimarães Pessôa, Fátima Higuera-de la Tijera, Juan Pablo Arab, Cláudia Alves Couto, Marco A. Arrese, Naim Alkhouri, Cristiane Alves Villela‐Nogueira, Sebastián Marciano, Pedro Montes, Cláudia P. Oliveira, Luis Antonio Díaz Piga, Zobair M. Younossi, Gustavo Ayares, Rafael Theodoro, Jeffrey V. Lazarus, Constanza D. Sabate, Daniel Cabrera, Mario Reis Alvares-da-Silva, Jorge Martínez Morales, Mazen Noureddin
article en

Abstract

Yes, FONDECYT #1241450 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. 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. 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). 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)

Annals of HepatologyVol. 29
Universidade Federal de Minas Gerais (BR), Pontificia Universidad Católica de Chile (CL), Universidade de São Paulo (BR), National University of Misiones (AR), Universidad de San Martín de Porres (PE), Hospital Italiano de Buenos Aires (AR), Hospital General de México (MX), University of California System (US), Universidade Brasil (BR), Daniel Alcides Carrión National University (PE), Hospital de Clínicas de Porto Alegre (BR), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (MX), Hospital Universitario Austral (AR), Hospital Universitário Clementino Fraga Filho (BR)
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