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. 2025 Jul 1;25(1):154.
doi: 10.1186/s12902-025-01977-2.

Evidence on the link between hypothyroidism and non-alcoholic fatty liver disease: an updated systematic review

Nazanin Pourseyedi  1 , Sara Arefhosseini  1 , Helda Tutunchi  2 , Mehrangiz Ebrahimi-Mameghani  3
Affiliations

Evidence on the link between hypothyroidism and non-alcoholic fatty liver disease: an updated systematic review

Nazanin Pourseyedi et al. BMC Endocr Disord. .

Abstract

Background: Numerous studies have investigated the relationship between hypothyroidism and non-alcoholic fatty liver disease (NAFLD), while the underlying mechanisms are not well understood. This systematic review evaluated the mentioned relationship among non-diabetic adults.

Methods: This systematic review was written in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar until January 2024. After a critical analysis, 29 observational studies were included in the present systematic review.

Results: The available observational evidence suggests a potential association between hypothyroidism and NAFLD. Regarding this complex relationship, patients with hypothyroidism may be more likely to develop NAFLD compared to those with normal thyroid function. Several factors are involved in the development of hypothyroidism-induced NAFLD.

Conclusions: Thyroid hormones regulate energy and metabolism, suggesting their relevance in NAFLD. Increased awareness and optimized strategies are needed for mutual screening and managing thyroid disease and NAFLD coexistence.

Keywords: Hypothyroidism; Non-alcoholic fatty liver disease; Non-diabetic adults; Observational studies.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of Tabriz University of Medical Science (IR.TBZMED.REC.1402.617). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable.

Figures

Fig. 1
Fig. 1
Flow diagram of the literature search and study selection process
Fig. 2
Fig. 2
Possible pathogenic effects of hypothyroidism on lipid homeostasis as a link between hypothyroidism and non-alcoholic fatty liver disease. SREBP-1c, Sterol regulatory element-binding protein-c; SREBP-2, Sterol regulatory element-binding protein-2; ChREBP, Carbohydrate-responsive element-binding protein; PPAR, Peroxisome proliferator-activated receptor; LDLR, Low-density lipoprotein receptor; AMPK, AMP-activated protein; HMG-CoA reductase, 3-hydroxy 3-methylglutaryl-coenzyme A; LDL-c, Low-density lipoprotein cholesterol; LPL, Lipoprotein lipase; NAFLD, Non-alcoholic fatty liver disease; TG, Triglycerides; TSH, Thyroid stimulating hormone; T4, Thyroxine; T3, Triiodothyronine
Fig. 3
Fig. 3
Proposed pathological consequences of hypothyroidism, linked to the progression of non-alcoholic fatty liver disease. REE, Resting energy expenditure; BMI, Body mass index; FFA, Free fatty acid; HOMA-IR, Homeostatic model assessment for insulin resistance; TSH, Thyroid stimulating hormone; T4, Thyroxine; T3, Triiodothyronine; IRS-1, Insulin receptor substrate-1; FGF-21, Fibroblast growth factor-21; NAFLD, Non-alcoholic fatty liver disease; PGC-1α, Peroxisome proliferator-activated receptor coactivator 1-alpha; NRF-1, Nuclear respiratory factor-1; CPT-1, Carnitine palmitoyltransferase-1; PINK1, PTEN-induced kinase-1; ERRα, Estrogen-related receptor-α; DAPK-2, Death-associated protein kinase-2; MED-1, Mediator complex subunit-1
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