Polyamine Dysregulation in Metabolic Dysfunction-associated Steatotic Liver Disease: a Systematic Review of Human Observational Evidence.
Alicia González-González, Lucía Aránega-Martín, Kamar Ouahbi-Chadli et al.
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In 30 seconds
This systematic review evaluated human observational evidence linking polyamines with MASLD severity and related hepatic or metabolic outcomes. It included nine studies, with more than 1,400 participants across clinical cohorts, as well as transcriptomic analyses. Increased hepatic putrescine and ornithine decarboxylase activity were associated with greater histological severity and hepatocellular injury in one study, while lower circulating or fecal spermidine was associated with greater severity in some studies. Results varied across studies, and none established diagnostic performance. The evidence therefore identifies candidate associations, not validated biomarkers or causal effects.
Key findings
- Nine studies comprising more than 1,400 participants were included; Newcastle-Ottawa Scale scores ranged from 6 to 9.
- In one study, increased hepatic putrescine and upregulated ornithine decarboxylase were associated with greater histological severity and hepatocellular injury.
- Lower spermidine in circulating and fecal samples was associated with greater disease severity in some studies.
- No included study established diagnostic performance using AUC, sensitivity, specificity, predefined cut-offs, or external validation.
Why it matters
Polyamine profiles may reflect metabolic, inflammatory, and microbial pathways associated with MASLD severity, making them plausible candidates for further biomarker research. However, heterogeneous observational findings and the absence of diagnostic validation mean their clinical utility is not established. Distinguishing promising biological associations from validated tools is important when interpreting potential additions to MASLD assessment.
What to keep in mind
The evidence was observational and heterogeneous, with variation in biological matrices, analytical approaches, and disease assessment methods. The review found no established diagnostic performance or external validation, limiting causal inference and conclusions about clinical utility.