# Association between trans-palmitoleic acid and metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma: NHANES 1999–2018

## TL;DR

This study explores how trans-palmitoleic acid (TPA) is linked to an increased risk of liver cancer in people with metabolic dysfunction-associated liver disease.

## Contribution

The study identifies TPA as a novel biomarker for predicting hepatocellular carcinoma risk in MASLD patients.

## Key findings

- TPA shows a strong nonlinear association with HCC risk, with risk escalating exponentially at higher TPA levels.
- TPA is linked to lipid dysregulation and is a significant predictor of HCC risk in non-diabetic populations.
- Women and younger individuals show heightened susceptibility to HCC risk at high TPA levels.

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health burden with an 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. Multivariable logistic regression and restricted cubic spline (RCS) models were employed to assess the association between TPA and HCC risk.

A striking nonlinear association between TPA and HCC risk was observed (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 a 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.