ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1606482
Association Between Trans-palmitoleic Acid and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Related Hepatocellular Carcinoma: NHANES 1999-2018
Provisionally accepted
- 1Zhejiang University, Hangzhou, China
- 2First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health burden with increasing incidence of hepatocellular carcinoma (HCC), yet early risk predictors remain elusive. This study investigated trans-palmitoleic acid (TPA) as a potential biomarker for MASLD-HCC risk using National Health and Nutrition Examination Survey (NHANES) data (n=548). Propensity score matching (PSM) minimized sociobehavioral confounders, while multivariable logistic regression and restricted cubic spline (RCS) models revealed a striking nonlinear association between TPA and HCC risk (P-nonlinear<0.001). Each unit increase in TPA elevated HCC risk by 52.4% (OR=1.524, 95%CI=1.397-1.677), with quartile analysis showing exponential risk escalation (Q4 OR=753.7). Subgroup analyses identified heightened susceptibility in women (Q4 OR=1148.83) and younger individuals (OR=612.11). TPA correlated positively with lipid factors (triglycerides β=1.236, LDL β=0.557) and hematologic indices, while exhibiting negative association with BMI (β=-0.037). Mediation analysis implicated triglycerides as a key metabolic intermediary (39.18% effect proportion). These findings establish TPA as an independent MASLD-HCC risk factor with distinct demographic variability, potentially mediated through lipid dysregulation. While limited by observational design, this study highlights TPA's prognostic value for HCC risk stratification, especially in non-diabetic populations (OR=257.14). Future mechanistic studies should validate TPA's oncogenic pathways and explore therapeutic targeting of trans-fatty acid metabolism to mitigate MASLD progression. The robust dose-response relationship and metabolic mediation effects position TPA as a promising candidate for incorporation into existing HCC prediction models.
Keywords: MASLD, HCC, Trans-palmitoleic acid, NHANES, MASLD-HCC
Received: 05 Apr 2025; Accepted: 21 May 2025.
Copyright: © 2025 Li, Zhan, Li, Zhu, Liu, Jiang, Cheng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lanjuan Li, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
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