Association Between Primary Hypothyroidism and MASLD: an updated meta-analysis

Background: Epidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between primary hypothyroidism and risk of MASLD. Methods: We systematically searched PubMed, Scopus, and Web of Science from database inception to January 31, 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging, or International Classification of Diseases codes. Meta-analysis was performed using random-effects modelling. Results: We identified 24 cross-sectional and four longitudinal studies with aggregate data on 76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement therapy, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects odds ratio 1.43, 95%CI 1.23-1.66; I2=89%). Hypothyroidism was also associated with a substantially higher risk of metabolic dysfunction-associated steatohepatitis or advanced fibrosis (n=5 studies; random-effects odds ratio 2.84, 95%CI 2.07-3.90; I2=0%). Meta-analysis of data from 4 longitudinal studies showed that there was a marginally non-significant association between hypothyroidism and risk of developing MASLD over a median 4.5-year follow-up (random-effects hazard ratio 1.39, 95%CI 0.98-1.97; I2=85%). Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. Conclusion: This large and updated meta-analysis provides evidence that primary hypothyroidism is significantly associated with both an increased presence of, and histological severity of MASLD.