ArticleFrontiers in medicine2026
Exploring potential associations between blood metabolites and cirrhosis risk: a Mendelian randomization and LC-MS/MS analysis.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The development of cirrhosis is closely intertwined with metabolic processes. No previous studies have reported a clear causal relationship between cirrhosis and metabolic processes. Thus, this study aimed to explore the potential associations between blood metabolites and cirrhosis using Mendelian randomization (MR) combined with targeted metabolomics analysis. Methods: A two-sample MR analysis was conducted using genome-wide association study data to evaluate the associations of circulating metabolites with cirrhosis. Statistical evaluations employed inverse variance-weighted models, MR-Egger regression, and sensitivity tests addressing pleiotropy and heterogeneity. In addition, blood samples were collected from 10 patients with liver cirrhosis and 10 healthy controls. Blood amino acid concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to provide preliminary clinical evidence supporting the MR-derived candidate metabolites. Results: The MR analysis found that increases in 11 metabolites/metabolic ratios were associated with elevated risks of liver cirrhosis, whereas increases in the remaining 3 metabolites were related to the prevention of the occurrence of liver cirrhosis. Among these candidates, genetically predicted higher glutamine degradant levels were associated with a lower risk of cirrhosis (OR = 0.877, 95% CI: 0.784-0.981, Conclusion: This study provides suggestive MR evidence linking specific circulating metabolites to cirrhosis risk. In particular, glutamine-related metabolic alterations may be associated with susceptibility to cirrhosis. These findings provide exploratory insights into metabolite-related pathways that may contribute to cirrhosis development.
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