S2543 Association Between Subclinical Hypothyroidism and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition that may progress to cirrhosis and hepatocellular carcinoma. While overt hypothyroidism has been linked to MASLD, the relationship between subclinical hypothyroidism (SCH) and MASLD remains controversial. Methods: We systematically searched PubMed, Embase, Cochrane, ClinicalTrials.gov, and Web of Science up to 12 February 2025 for studies evaluating the association between SCH and MASLD. Random-effects meta-analyses were performed on eligible cross-sectional and longitudinal studies. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated with funnel plots and Egger’s test. Sensitivity analyses, including leave-one-out approaches and trim-and-fill methods, were conducted to gauge robustness. Results: After examining the titles and abstracts of these publications and excluding duplicates, we identified 191 potentially eligible studies from 5 large electronic databases (PubMed, Web of Science, Embase, Cochrane, clinicaltrials.gov) from the inception to February 22, 2025. After comparing those 191 studies with our inclusion and exclusion criteria, we ended up selecting Ten high-quality, peer-reviewed studies involving 75,618 patients were included (6 cross-sectional, 4 longitudinal). In cross-sectional analyses (n = 40,063), SCH was associated with a 42% higher odds of MASLD (pooled OR = 1.42, 95% CI 1.15–1.60; I² = 0%). Among 4 longitudinal studies (n = 31,541), SCH conferred a 65% increased risk of incident MASLD (pooled HR = 1.65, 95% CI 1.02–2.67) but with substantial heterogeneity (I² = 84%). Egger’s regression showed a significantly nonzero intercept (β₁ = 3.00, z = 2.38, P = 0.0171), and the funnel plot was visibly asymmetric, pointing to small‐study or publication bias. Therefore a leave one out test was done by leaving out 1 of the studies that improved both the effect size (HR = 1.88, 95% CI 1.45–2.44) and reduced heterogeneity (I² = 0%). Conclusion: This meta-analysis provides evidence that SCH is associated with both higher odds of prevalent MASLD and increased risk of incident MASLD. Clinicians should consider routine screening for MASLD in patients with SCH and vice versa. Future research is needed to determine whether therapeutic interventions for SCH can prevent or slow MASLD progression.