International Journal of Gastroenterology and Hepatology (ISSN: 2995-2301) | Volume 5, Issue 1 | Research Article | Open Access DOI
Prof. Debmalya Sanyal, MD, DM*
Dr. Girin Ray, MBBS¹, Prof. Debmalya Sanyal, MD, DM2*
¹Post Graduate Trainee, Department of General Medicine, KPC Medical College and Hospital, Kolkata, India
²Professor, Department of Endocrinology, KPC Medical College and NHRTIICS, Kolkata, India
*Correspondence to: Prof. Debmalya Sanyal, MD, DM
Fulltext PDFContext: The global transition in hepatological nomenclature to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) highlights the role of systemic metabolic dysregulation in liver pathology. Hypothyroidism is a prevalent endocrine disorder that has been linked to severe metabolic dysfunction. The present systematic review aimed to determine the overall risk of MASLD and advanced fibrosis in hypothyroid populations and evaluate the therapeutic efficacy of novel liver-directed thyromimetics.
Methods: To obtain the related data, major electronic databases, including PubMed, Embase, MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials, were searched. The full texts of articles presenting data on MASLD prevalence in thyroid dysfunction, foundational mechanisms, and clinical trials of thyroid hormone receptor-beta (THR-β) agonists were screened and retrieved. The odds ratio (OR) and hazard ratio (HR) of MASLD outcomes were synthesized using random-effects models. Heterogeneity was evaluated using the I2 statistic. A two-tailed P<0.05 was considered statistically significant.
Results: High-powered epidemiological pooling demonstrates a significant association between primary hypothyroidism and MASLD. The pooled prevalence indicates that hypothyroidism confers a 43% increased risk for prevalent MASLD (OR 1.43, 95% CI: 1.23–1.66, I2 = 89%) and a nearly three-fold risk for advanced histological severity, including MASH and bridging fibrosis (OR 2.84, 95% CI: 2.07–3.90, I2 = 0%). Mechanistically, this is driven by localized "hepatic hypothyroidism." In the therapeutic domain, Phase 3 trials of the THR-agonist Resmetirom achieved significantly higher MASH resolution compared to placebo (up to 29.9% vs. 9.7%, P<0.05), establishing a new paradigm in structural disease reversal.
Conclusions: In conclusion, the presence of primary hypothyroidism is associated with a significantly increased risk of developing MASLD and advanced fibrosis. The subpopulation of patients with intersecting metabolic syndrome and thyroid dysfunction must be actively screened. Furthermore, restoring the thyroid-liver axis via targeted thyromimetics represents a highly effective, disease-modifying intervention.
Hypothyroidism; Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD); Advanced fibrosis; thyromimetics
Girin Ray, Debmalya Sanyal. Systematic Review and Meta-analysis of the Thyroid-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease. Int Jour Gastro Hepat. 2026;5(1):1-9.