ESTEATOSE HEPÁTICA METABÓLICA EM PORTADORES DE DIABETES MELLITUS TIPO 2: CARACTERÍSTICAS CLÍNICAS, ESTIMATIVA DOS GRAUS DE FIBROSE E FATORES ASSOCIADOS À PROGRESSÃO

• Ano de defesa: 2025
• Autor(a) principal: FRANÇA DE ABREU, Joana D’Arc Matos
• Orientador(a): FERREIRA, Adalgisa de Sousa Paiva
• Banca de defesa: FERREIRA, Adalgisa de Souza Paiva , BECKMAN, Adriana Maria Guimarães Sá , PAES, Antônio Marcus de Andrade , NASCIMENTO, Gilvan Cortês , RODRIGUES, Vandilson Pinheiro
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Maranhão
• Programa de Pós-Graduação: PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS
• Departamento: COORDENAÇÃO DO CURSO DE MEDICINA/CCBS
• País: Brasil
• Palavras-chave em Português: Esteatose Hepática Metabólica; Diabetes Mellitus Tipo 2; Fibrose Hepática; Elastografia; Testes Não Invasivos; Ancestralidade Genômica; Disfunção Metabólica
• Palavras-chave em Inglês: Metabolic dysfunction-associated steatotic liver disease; Type 2 diabetes mellitus; Hepatic fibrosis; Transient elastography; Noninvasive tests; Genomic ancestry; Metabolic dysfunction
• Área do conhecimento CNPq: Endocrinologia
• Link de acesso: https://tedebc.ufma.br/jspui/handle/tede/6674

Metabolic dysfunction–associated steatotic liver disease (MASLD) affects approximately 30% of the global population and more than 60% of individuals with type 2 diabetes mellitus (T2DM), representing an increasingly significant cause of hepatic and cardiovascular morbidity and mortality. In highly admixed populations, such as the Brazilian population, the metabolic and genomic determinants of liver fibrosis remain insufficiently understood, hindering risk stratification and the implementation of personalized management strategies. This study aimed to investigate the clinical, laboratory, and genomic factors associated with liver fibrosis in patients with T2DM and MASLD receiving care at a referral endocrinology center in Northeastern Brazil, and to assess the accuracy of noninvasive methods for the detection of advanced fibrosis. This was a cross-sectional study conducted between July 2022 and February 2024 in adults with T2DM and confirmed diagnosis of MASLD by transient elastography (FibroScan®). The research was structured into two components: the first included 240 patients and evaluated clinical-epidemiological and laboratory factors associated with liver fibrosis, as well as the performance of the FIB-4 and MAF-5 noninvasive tests; the second component analyzed 212 patients to investigate the association between genomic ancestry (European, African, and Native American) and the severity of liver fibrosis and steatosis, based on ancestry-informative markers and transient elastography parameters. In the first component, female sex (adjusted OR = 2.69; p = 0.005), obesity (adjusted OR = 2.23; p = 0.009), and elevated AST, ALT, and GGT levels were independently associated with the presence of liver fibrosis, even after multivariable adjustments. The FIB-4 and MAF-5 scores demonstrated good accuracy in predicting significant fibrosis, confirming their clinical utility in resource-limited settings. In the second component, European ancestry predominated (56.5%), followed by African (26.0%) and Native American (17.5%) ancestry. No statistically significant associations were observed between genomic ancestry and the severity of liver fibrosis or steatosis (p > 0.05). These findings reinforce that metabolic dysfunction, particularly obesity and dyslipidemia, is the major driver of liver disease progression, regardless of individual genomic background in highly admixed populations. In adults with T2DM and MASLD, the severity of liver fibrosis is predominantly determined by metabolic factors independent of genomic ancestry. The use of noninvasive tests such as FIB-4 proved effective for the screening of advanced fibrosis in public health settings, whereas genomic analysis did not indicate a meaningful influence of ancestry on disease course. These results emphasize the importance of stringent metabolic control and an integrated clinical approach in the management of MASLD in individuals with diabetes.