Clin Mol Hepatol.
2025 Feb;31(Suppl):S76-S93. 10.3350/cmh.2024.0438.
Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease
- Affiliations
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- 1Department of Biomedical Sciences, Unit of Oncology and Molecular Pathology, University of Cagliari, Cagliari, Italy
- 2Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy
- 3Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- 4Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
- 5Department of Medicine, Endocrinology (H7) Karolinska Institute and Hospital, Huddinge, Stockholm, Sweden
- KMID: 2565372
- DOI: http://doi.org/10.3350/cmh.2024.0438
Abstract
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex multifactorial disease and becoming the leading cause of liver-related morbidity and mortality. MASLD spans from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may progress to cirrhosis and hepatocellular carcinoma (HCC). Genetic, metabolic, and environmental factors strongly contribute to the heterogeneity of MASLD. Lifestyle intervention and weight loss represent a viable treatment for MASLD. Moreover, Resmetirom, a thyroid hormone beta receptor agonist, has recently been approved for MASLD treatment. However, most individuals treated did not respond to this therapeutic, suggesting the need for a more tailored approach to treat MASLD. Oligonucleotide-based therapies, namely small-interfering RNA (siRNA) and antisense oligonucleotide (ASO), have been recently developed to tackle MASLD by reducing the expression of genes influencing MASH progression, such as PNPLA3 and HSD17B13. Here, we review the latest progress made in the synthesis and development of oligonucleotide-based agents targeting genetic determinants of MASH.
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