Metabolic risk factors including diabetes and metabolic syndrome are associated with increased hepatocellular carcinoma riskMetabolic risk factors linked to higher liver cancer risk

Frontiers in Medicine Published August 29, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Note that metabolic risk factors, particularly diabetes and metabolic syndrome, are associated with increased HCC risk.

This meta-analysis synthesized data from cohort studies involving more than 45 million participants to evaluate the association between various metabolic risk factors and the risk of hepatocellular carcinoma (HCC). The analysis included metrics such as metabolic syndrome, diabetes mellitus, body mass index (BMI), and various lipid levels.

Key findings indicate that metabolic syndrome (1.80; 95%CI: 1.44-2.25), diabetes mellitus (2.01; 95%CI: 1.79-2.27), and a waist-to-height ratio (2.23; 95%CI: 1.42-3.51) are positively associated with increased HCC risk. Other factors associated with increased risk include BMI $\geq$ 24 kg/m2 (1.47; 95%CI: 1.35-1.61), waist circumference (1.39; 95%CI: 1.26-1.55), waist-to-hip ratio (1.33; 95%CI: 1.16-1.52), and hypertension (1.43; 95%CI: 1.13-1.81). Reduced triglyceride levels were also associated with increased risk (1.36; 95%CI: 1.09-1.69).

Conversely, elevated high-density lipoprotein cholesterol (0.88; 95%CI: 0.81-0.96) and reduced high-density lipoprotein cholesterol (0.96; 95%CI: 0.93-0.99) were associated with decreased risk. Elevated low-density lipoprotein cholesterol (0.44; 95%CI: 0.32-0.62) also showed a decreased risk association. Total cholesterol and elevated triglyceride levels did not show significant associations with HCC risk. These findings may inform screening strategies for patients with high-risk metabolic profiles.

How this fits prior evidence

This meta-analysis addresses a gap in understanding the role of metabolic risk factors in hepatocellular carcinoma. While previous coverage has focused on diagnostic markers like radiomic features, prognostic factors like the Immune Health Index, and therapeutic interventions such as PD-(L)1 plus VEGF combinations, this study provides evidence on the association between metabolic profiles and HCC risk. Specifically, it identifies diabetes mellitus and metabolic syndrome as significant risk factors, which may complement existing knowledge on risk stratification.

Living with metabolic issues like diabetes or high blood pressure can have impacts that go beyond daily symptoms. A large-scale analysis of over 45 million people found that these specific risk factors are linked to a higher chance of developing hepatocellular carcinoma, a common type of liver cancer.

The study looked closely at several markers. It found that having diabetes, a high body mass index, and a larger waist circumference were all associated with increased risk. Specifically, a high waist-to-height ratio showed a strong link to the cancer. These findings suggest that managing metabolic health might be a key part of long-term liver health.

While the data shows a clear connection between these conditions and liver cancer, it is important to remember that these are associations, not direct causes. The study also noted that some factors, like total cholesterol, did not show a significant link. Because these results come from large group studies, talk to your doctor about what these specific risks mean for your personal health plan.

What this means for you:

Conditions like diabetes and high blood pressure are linked to an increased risk of liver cancer.

Common questions

What metabolic conditions are linked to liver cancer?

The study found that several factors are linked to an increased risk of hepatocellular carcinoma. These include diabetes mellitus, metabolic syndrome, high blood pressure, and a high body mass index. Specifically, a larger waist circumference and a higher waist-to-height ratio were also associated with increased risk.

Does high cholesterol affect liver cancer risk?

The results for cholesterol were mixed. While elevated high-density lipoprotein cholesterol and elevated low-density lipoprotein cholesterol were associated with a decreased risk, total cholesterol was not significantly associated with liver cancer risk in this study of over 45 million people.

Does this mean these conditions cause liver cancer?

The study shows a link between these metabolic factors and liver cancer, but it does not prove that one causes the other. Because these are associations rather than direct causes, you should speak with your doctor to understand how these findings apply to your specific health situation.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJul 2026

View Original Abstract ↓

BackgroundConsiderable evidence suggests that hepatocellular carcinoma (HCC) is tightly related to metabolic disorders. However, it is not yet clear which metabolic risk factors play a critical role in hepatocarcinogenesis.MethodsWe searched Pubmed, Embase, and Web of Science from inception up to April 29, 2023. The hazard ratio (HR) and the corresponding 95% confidence interval (95%CI) were used to assess the pooled risk.ResultsSeventy-three studies involving more than 45 million participants were included. Among the metabolic risk factors: metabolic syndrome (MetS) (HR = 1.80, 95%CI: 1.44–2.25), diabetes mellitus (DM) (HR = 2.01, 95%CI: 1.79–2.27), body mass index (BMI) ≥ 24 kg/m2 (HR = 1.47, 95%CI: 1.35–1.61), waist circumference (WC) (HR = 1.39, 95%CI: 1.26–1.55), waist-to-hip ratio (WHR) (HR = 1.33, 95%CI: 1.16–1.52), waist-to-height ratio (WHtR) (HR = 2.23, 95%CI: 1.42–3.51), reduced triglyceride (TG) (HR = 1.36, 95%CI: 1.09–1.69) and hypertension (HR = 1.43, 95%CI: 1.13–1.81) were positively associated with HCC risk. The disturbances of high-density lipoprotein cholesterol (HDL-C) levels (elevated, HR = 0.88, 95%CI: 0.81–0.96; reduced, HR = 0.96, 95%CI: 0.93–0.99) and elevated low-density lipoprotein cholesterol (LDL-C) (HR = 0.44, 95%CI: 0.32–0.62) were consistently associated with decreased risk of HCC. Nevertheless, elevated total cholesterol (TC) (HR = 0.87, 95%CI: 0.69–1.10) and elevated TG (HR = 0.72, 95%CI: 0.36–1.43) were not significantly associated with HCC risk.ConclusionAdverse metabolic risk factors are associated with an increased risk of HCC, which may provide new insights into HCC screening strategies for patients with these risk factors.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023401883.

Metabolic risk factors including diabetes and metabolic syndrome are associated with increased hepatocellular carcinoma riskMetabolic risk factors linked to higher liver cancer risk

How this fits prior evidence

Common questions

Study Details

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