SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Cancer Metabolism
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1644677
Inverse Association Between Serum Lipid Profiles and Hepatocellular Carcinoma Risk: A Meta-Analysis of Epidemiological Studies
Provisionally accepted
- 1China Three Gorges University School of Science and Technology, Yichang, China
- 2College of Biological Science and Engineering,, Fuzhou University, Fuzhou, China
- 3College of Biological Science and Engineering, Fuzhou University, Fuzhou, China
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Background: The relationship between serum lipid profiles and hepatocellular carcinoma (HCC) risk remains controversial. We aimed to clarify this association through a systematic meta-analysis of epidemiological studies. Methods: A systematic literature search was conducted in PubMed, Embase, and Web of Science (2000–May 2023) for prospective, retrospective, and cross-sectional studies reporting adjusted risk estimates (HR/OR) of HCC associated with serum lipids. Pooled effect sizes were calculated using random-effects models, with heterogeneity assessed via Cochran's Q and I² statistics. Results: Twenty-three studies (16 cohorts, 7 case-control) involving 1.2 million participants ((including both healthy individuals and patients with chronic liver diseases) ) were included. Elevated serum total cholesterol (TC) was inversely associated with HCC risk (HR=0.71, 95% CI: 0.64–0.78; I²=0%). Similar protective effects were observed for high LDL (HR=0.46, 95% CI: 0.36–0.59; I²=97%), triglycerides (HR=0.79, 95% CI: 0.62–0.99; I²=94%), and dyslipidemia (HR=0.64, 95% CI: 0.50– 0.83; I²=81%). No significant association was found for high-density lipoprotein (HDL). Sensitivity analyses confirmed robustness for TC and LDL, while TG results were influenced by a single study. Conclusion: This meta-analysis provides robust evidence that elevated serum cholesterol and specific lipid subfractions are associated with reduced HCC risk. Further mechanistic studies are warranted to elucidate the role of lipid metabolism in hepatocarcinogenesis.
Keywords: Meta-analysis, liver cancer, risk, Serum lipid, Cholesterol, HDL, LDL, Triglycerides
Received: 10 Jun 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Zeng, Liu, Li and Han. 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: Xiao Han, hanxiao@fzu.edu.cn
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