@article{10902/34182,
year = {2024},
url = {https://hdl.handle.net/10902/34182},
abstract = {Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was per formed using the fgsea R package with a preranked “limma t-statistic” gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p <0.001) and advanced MASLD (12.8% vs. 2.8%; p <0.001) prevalence were significantly higher among patients with IMID than controls. In multivariate analysis, concomitant IMID was an independent, and the strongest, predictor of advanced SLD (adjusted odds ratio 3.318; 95% CI 2.225-4.947; p <0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. Conclusions: The prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyze a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies.},
organization = {Acknowledgments: This work was fully suported by grants from the Spanish Instituto de Salud Carlos III (ISCIII-FEDER). Grant numbers: PI18/01304, PI20/01279, and PI19/00204},
organization = {This work was fully suported by grants from the Spanish Instituto de Salud Carlos
III (ISCIII-FEDER). Grant numbers: PI18/01304, PI20/01279, and PI19/00204.},
publisher = {Elsevier},
publisher = {JHEP Reports, 2024, 6 (10), 101167},
title = {Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases},
author = {García Nieto, Enrique and Rodríguez Duque, Juan Carlos and Rivas Rivas, Coral and Iruzubieta Coz, Paula and García, María José and Rasines, Laura and Álvarez Cancelo, Laura and García Blanco, Agustín and Fortea, José Ignacio and Puente, Ángela and Castro, Beatriz and Cagigal, María Luisa and Rueda-gotor, Javier and Blanco, Ricardo and Vaqué Díez, José Pedro and Crespo, Javier and Arias-Loste, María Teresa},
}