A systematic review and meta-analysis examining the relationship between hyperthyroidism or hypothyroidism and the probability of developing liver cancer.

BACKGROUND: Observational studies have reported inconsistent associations between hypothyroidism or hyperthyroidism and risk of liver cancer (LC). We therefore conducted a systematic review and meta-analysis to investigate the relationship between thyroid dysfunction and LC risk, and to explore the potential clinical implications of thyroid-related metabolic disturbances in liver carcinogenesis. METHODS: To identify eligible studies, we searched electronic databases including PubMed/Medline, ISI, Web of Science, and Scopus, up to March 2025. We also used fixed and random effects models to calculate effect sizes (ESs) and 95% confidence intervals (CIs) to detect association between hypothyroidism or hyperthyroidism, and the risk of LC. RESULTS: Five observational studies, with a total sample size of 3,206,891 individuals and 708 cases of LC, were included in this systematic review and meta-analysis. Pooling two effect sizes from case-control studies showed no significant association between hypothyroidism and risk of LC (Combined effect size: 1.31, 95% CI: 0.68–2.49, P = 0.413). However, by pooling two effect sizes from cohort studies it was found that there was an association between hypothyroidism and LC risk (Combined effect size: 1.45, 95% CI: 1.08–1.95, P = 0.012). Moreover, combining three effect sizes from cohorts revealed no significant association between hyperthyroidism (Combined effect size: 1.10, 95% CI: 0.90–1.34, P = 0.337) and risk of LC. CONCLUSIONS: The present meta-analysis showed that there are associations between hypothyroidism and LC risk in the cohort studies. However, there is no association between hyperthyroidism and the risk of LC. These findings suggest that thyroid dysfunction, particularly hypothyroidism, may play a clinically relevant role in liver carcinogenesis through metabolic and hormonal pathways. Early detection and management of thyroid abnormalities might therefore be important in individuals at risk of liver cancer. REGISTRATION NUMBER: PROSPERO CRD42022331093.