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Abstract
Objective 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 the risk of MASLD.
Design We systematically searched PubMed, Scopus and Web of Science from database inception to 31 January 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging or International Classification of Diseases codes. A meta-analysis was performed using random-effects modelling.
Results We identified 24 cross-sectional and 4 longitudinal studies with aggregate data on ~76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement treatment, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects OR 1.43, 95% CI 1.23 to 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 OR 2.84, 95% CI 2.07 to 3.90; I2=0%). Meta-analysis of data from four 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 HR 1.39, 95% CI 0.98 to 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.
- meta-analysis
- nonalcoholic steatohepatitis
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
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Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Footnotes
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Contributors AM and GT were involved in the conception of the study, the analysis and interpretation of the results and wrote the first draft of the manuscript. AC, NB, JB, BP, ES and RM were involved in the conduct of the study and searched the published articles. JB, SAP, LV, HT and CDB were involved in the interpretation of the results and contributed to the discussion. All authors edited, reviewed and approved the final version of the manuscript. GT is the guarantor of the study who accept full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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