ArticlePloS one2025
Identification of potentially effective drugs for metabolic dysfunction-associated steatotic liver disease against liver cirrhosis: In-silico drug repositioning-based retrospective cohort study.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- CauReL: Dynamic Counterfactual Learning for Precision Drug Repurposing in Alzheimer's Disease.Research square · 2025Article
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4 authors.
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Abstract
backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for liver cirrhosis, yet effective prevention or treatment strategies remain limited. To address this, we utilized a signature-based in silico drug repositioning approach to identify potential therapeutics for MASLD that may reduce the risk of cirrhosis.
methodsWe analyzed gene expression datasets to identify differentially expressed genes (DEGs) in MASLD and matched them to candidate drugs using L1000CDS2. We further validated potential drugs by cross-referencing with prescription data from the Korea National Health Insurance Service (NHIS). Participants who underwent health screenings between 2013 and 2014 were included. MASLD was diagnosed in individuals with hepatic steatosis (fatty liver index ≥60) and at least one cardiometabolic risk factor.
resultsWe identified 11 drug candidates and analyzed 49,555 MASLD patients (mean age: 63.0 years, SD: 8.6). Atenolol (SHR: 0.81; 95% CI: 0.72-0.92; P < 0.001), isosorbide dinitrate (SHR: 0.82; 95% CI: 0.73-0.93; P = 0.001), and valsartan (SHR: 0.52; 95% CI: 0.45-0.60; P < 0.001) were associated with a reduced risk of cirrhosis. Conversely, amlodipine-based combinations (SHR: 1.24; 95% CI: 1.11-1.39; P < 0.001), torasemide (SHR: 1.39; 95% CI: 1.24-1.56; P < 0.001), and valsartan-based combinations (SHR: 1.22; 95% CI: 1.09-1.37; P < 0.001) were linked to an increased risk.
conclusionsOur findings suggest that antihypertensive drugs such as atenolol and isosorbide dinitrate may protect MASLD patients from cirrhosis, providing valuable insights for clinical applications and treatment strategies. LIMITATIONS: This study is limited to drugs registered in the Korean NHIS, potentially excluding other relevant candidates. Additionally, the absence of dietary and genetic data in the NHIS database may introduce residual confounding. Lastly, as the study population consists solely of Korean adults, the findings may not be generalizable to other populations.
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